Dose-effect analysis of treatment by modified Zhibaidihuang decoction on polycystic ovary syndrome hyperandrogenism

INTRODUCTION

Polycystic ovary syndrome(PCOS)is one of the most common endocrine disorders in reproductive-age women with an estimated prevalence rate of 5%-10%,1,2and it is characterized by chronic oligo-anovulation,clinical and/or biochemical hyperandrogenism and polycystic ovaries. Hyperandrogenism (HA) is found in 60%-80%of PCOS patients.3HA includes clinical and biochemical manifestations,and the main performance of the former is acne and hirsutism.PCOS women of our country are with more acne and less hirsutism.4Moreover,it will take a long period of time for hirsutism to be improved effective.

Reducing androgen is the important component of the basic treatment of PCOS.Currently,the treatment methods of Traditional Chinese Medicine(TCM)in reducing androgen include smoothing liver andand purging fire,5,6regulating kidney and clearing lung7and reinforcing kidney and dissolve phlegm,8etc.,which all have varying extent of efficacy.Our previous clinical observation found that PCOS HA had relationship with kidney-Yindeficiency and hyperactivity of fire,9and modified Zhibaidihuang decoction(MZBDD)had efficacy on treatment of PCOS HA by reducing serum testosterone(T)and acne score.Of which,the dose of the main herbs Huangbai(Cortex Phellodendri Amurensis),Zhimu(Rhizoma Anemarrhenae)and Dihuang(Radix Rehmanniae)were all 30 g.10The dosage of herbs directly effects on the efficacy ofTCM.11Is 30 g the optimum dose in reducing PCOS HA?Does lower dose have the ideal treatment outcome?The objective of this paper is to observe the therapeutic effect of different dosages of MZBDD on PCOS HA patients in order to provide the basis for its clinical application.

我国大部分煤层透气性较低，不仅阻碍煤层气开发，还极易引起瓦斯灾害，严重威胁人们的生命财产安全。低渗透煤层取得良好抽采效果的关键在于强化增透，为了提高煤层渗透性，国内学者一直寻求多种煤层卸压增透的技术方法。煤层增透技术主要有水力冲孔[1-2]、水力割缝[3]、水力压裂[4-5]等，但是这些增透方法对实际工程运用有一定的局限性。近年来，一些学者尝试用液氮等低温流体注入煤岩、砂岩等物质，以达到冷裂岩体的目的[6-8]，相比于水力压裂、水力冲孔等技术，液氮冷裂具有节约水资源、对环境污染小等优势，能有效提高煤储层渗透性，已经开始受到国内外研究者的关注。

Of 81 PCOS HA cases,32 cases were with bipolar BBT.The BBT biphasic rate was 39.5%.There was no remarkable difference with BBT biphasic rate among the three groups(P=0.510)(Figure 5).

MATERIALS AND METHODS

Diagnostic criteria

PCOS was diagnosed according to the Rotterdam criteria provided by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology.12A diagnosis of PCOS was made if at least two of the following criteria were met:(a)oligo/anovulation,(b)signs of hyperandrogenism(i.e.,hirsutism and acne)and/or biochemical measurements,(c)enhanced ovaries(at least 12 discrete follicles of 2-9 mm in diameter in one ovary or the ovarian volume＞10 cm3observed by transvaginal ultrasonography).Women with other androgen-excess disorders or specific etiologies including congenital adrenal hyperplasia,Cushing's syndrome,thyroid hormone abnormalities,hyperprolactinemia,or ovarian/adrenal tumors were excluded.

实现高校基层党建工作常态化模式是高校教育体制改革的重点内容，有利于高校教学水平和质量的提升，为社会主义建设和发展培养出更多优秀的人才，促进大学生的全面发展[3]。创新高校基层党建常态化工作模式，就需要遵循一个中心两个结合的原则，积极履行党建工作的基本职责，推动基本党建在高校大学生管理中的作用，提高大学生管理水平和效率。

Inclusion criteria

Corresponding to the diagnosis criteria of PCOS;the level of serum T was higher than the criterions(＞0.569 ng/mL);within the age range of 18-35 years old;voluntarily joined the clinical observation and signed informed consent.

3.多媒体应用到高职韩国语教学中能缓解课程内容多、学时少的矛盾。在高职韩国语课程中，学习内容较多，而课时相对较少，为了使学生在有限的课时内学到更多知识，必然要改变原有的教学模式和手段，多媒体技术运用图片、声音、视频、慕课等形式，将枯燥乏味的知识点转换为直观形象，可以使高职韩国语学生更深刻地理解相关知识点，提高学习兴趣。

Exclusion criteria

Complicated with endocrine diseases such as thyroid or adrenal disorders,diabetes;complicated with severe cardiac,pulmonary,hepatic,renal or neurological disease or mental illness;complicated with thrombotic diseases;Use of hormonal drugs(except for progesterone)or any other drugs which can affect reproductive endocrinein thepast12 weeks;body massindex(BMI)≥24.

Case sources

Ninty PCOS women,who asked for treatment at the department of gynocology of Guang'an men Hospital,China Academy of Chinese Medical Sciences from June 2014 to May 2015 and corresponding to inclusion criteria and exclusion criteria,were divided into high dosage group(HDG),medium dosage group(MDG)and low dosage group(LDG)by random number with 30 women in each group according to the random number table.And 30 infertile patients due to tubal factor were selected.

青皮药材的HPLC指纹图谱建立及聚类分析和主成分分析…………………………………………………… 靳贝贝等（24）：3336

Treatment method

The PCOS HA patients all used Zhibaidihuang decoction [Huangbai (Cortex Phellodendri Amurensis),Zhimu(RhizomaAnemarrhenae),Dihuang (Radix Rehmanniae)]which were decocted by Guang'anmen Hospital as a basic treatment.The recipe in LDG consisted of Zhimu(Rhizoma Anemarrhenae)10 g,Huangbai(Cortex Phellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g.The recipe in MDG consisted of Zhimu(Rhizoma Anemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g.The recipe in HDG consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g.Yinyanghuo(Herba Epimedii Brevicornus)and Tusizi(Semen Cuscutae)were added for deficiency of kidney-Yang.Stir-frying Baizhu(Rhizoma Atractylodis Macrocephalae)was added for deficiency of spleen-Qi.Baishao(Radix Paeoniae Alba)and Muli(Concha Ostreae)were added for hyperactivity of liver-Yang.Stir-frying Suanzaoren(Se-men Ziziphi Spinosae)was added for insomnia.The decoction was orally taken,one dose a day,in the morning and in the evening on an empty stomach,from the fifth day of the menstrual cycle for 4 weeks as a course of treatment.All patients gave informed consent.

Measurements and outcomes

2 Practice Committee of the American Society for Reproductive Medicine.Fertil Steril 2006;86(5):S241-S247.

Statistical analysis

Statistical analysis was performed with statistical package for the social science(SPSS Inc.,Chicago,IL,USA)version 19.0.Measurement data presented as mean±standard deviation(xˉ±s)and were analyzed by analysis of variance(ANOVA),paired-samplet-test,Count data were analyzed using the χ2.AP ＜0.05 was considered as significant.

RESULTS

Baseline data

Ninety PCOS women were recruited of which 81 finished the research and entered the analysis the number of patients in HDG,MDG and LDG was 30,24 and 27,respectively.And for the 30 NCG patients,they all finished the research.Seventy-nine cases were married while 32 cases were unmarried;age differs from 19 to 35,average(26.7±3.8);BMI differ from 17.06 to 23.92,average(20.8±1.7).There were no statistical differences with respect to baseline features like age,BMI,waistline and waistline hipline ratio(WHR)(P=0.767,P=0.310,P=0.731)(Figure 1).

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Serum T

14 Deng TT.Traditional Chinese Medicine diagnostics.Shanghai:Shanghai Science and Technology Press,1984:122.

Figure 1 Clinical characteristics at baseline of the four groups

HDG:high dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g];MDG:medium dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g];LDG:low dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)10 g,Huangbai(Cortex Phellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g];NCG:normal control group.BMI:body mass index;WHR:waistline and waistline hipline ratio.

Serum Sex-hormone Concentration

There was no significantly difference in serum FSH,LH,E2,P and PRL among the four groups before treatment(as for FSH,P=0.104;as for LH,P=0.101;as for E2,P=0.205;as for P,P=0.054;as for PRL,P=0.375).And there was no significantly difference among the HDG,MDG and LDG between before and after treatment(as for FSH,P=0.136,P=0.503,P=0.062;as for LH,P=0.473,P=0.513,P=0.096;as for E2,P=0.206,P=0.927,P=0.076;as for PRL,P=0.120,P=0.903,P=0.407;as for P,P=0.308,P=0.866,P=0480),but FSH,E2and P had different degrees of increasing trend(Figure 3).

Acne scores

Compared with before treatment,the acne scores of all the three PCOS HA groups were lower than that of after treatment(P=0.031,P=0.033,P=0.002),especially in HDG(P=0.002)(Figure 4).

BBT

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Liver function

There were no significantly differences with ALT and AST among the four groups before treatment.And also no significantly differences after treatment compared with before treatment among the LDG,MDG and HDG(as for ALT,P=0.742,P=0.383,P=0.053;as for AST,P=0.732,P=0.519,P=0.120)(Figure 6).

DISCUSSION

Figure 2 Comparison of serumT among the four groups

HDG:high dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g];MDG:medium dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g];LDG:low dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)10 g,Huangbai(Cortex Phellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g];A:change of serum T among the HDG,MDG and LDG before and after treatment;B:percentage of serum T decreased in the HDG,MDG and LDG compared to before treatment;C:decrease of serum T concentration among the HDG,MDG and LDG.T:serum total testosterone;HDG:high dosage group;MDG:medium dosage group;LDG:low dosage group;NCG:normal control group.aP＜0.05,as compared with the datum before treatment;bP＜0.01 as compared with the datum before treatment;cP＜0.05,as compared with the datum of NCG.

Figure 3 Comparison of sex-hormone among the HDG,MDG and LDG before and after treatment

HDG:high dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g];MDG:medium dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g];LDG:low dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)10 g,Huangbai(Cortex Phellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g].NCG:normal control group;A:serum FSH;B:serum LH;C:serum E2;D:serum P;E:serum PRL;F:serum T.T:serum total testosterone;E2:estrodial;FSH:follicle stimulating hormone;LH:luteinizing hormone;PRL:prolactin;HDG:high dosage group;MDG:medium dosage group;LDG:low dosage group;NCG:normal control group.aP＜0.05,as compared with the datum before treatment;bP＜0.01,as compared with the datum before treatment;cP＜0.05,as compared with the datum of NCG.

Zhibaidihuang decoction originated fromYi Zong Jin Jianwhich was composed by herbs such as Huangbai(Cortex Phellodendri Amurensis),Zhimu(Rhizoma Anemarrhenae),Dihuang(Radix Rehmanniae),Mudanpi(Cortex Moutan Radicis),Shanzhuyu(Fructus Macrocarpii),Shanyao(Rhizoma Dioscoreae Oppositae),Fuling(poria),and Zexie(Rhizoma Alismatis).It has a role of nourishingYinand releasing fire so that it can work onYindeficiency and Fire exuberance syndrome.Our previous clinical observation showed that MZBDD could treat PCOS hyperandrogenism which performance as kidney-Yindeficiency and hyperactivity of fire.Chinese herbs had complex components.Zhibaidihuang decoction consisted of 8 herbs which was not conducive to the active ingredients analysis and mechanism research.It was necessary to streamline and optimize Zhibaidihuang decoction in order to make a foundation for the following research.The herbs which had a role of nourishingYinand releasing fire should be selected according to the type of syndrome of PCOS hyperandrogenism.Therefore,this observation selected three herbs-Huangbai(Cortex Phellodendri Amurensis),Zhimu(Rhizoma Anemarrhenae),and Dihuang(Radix Rehmanniae).All the three herbs'dosage had changed great since the Han Dynasty.The dosage of Huangbai(Cortex Phellodendri Amurensis)was largest in Han and Tang Dynasties when Huangbai(Cortex Phellodendri Amurensis)was used up to 220 g per prescription in Tang Dynasty while maintained a large dosage with a usual range of 8-40 g in Song Dynasty.From Jin and Yuan Dynasty to now,the use of Huangbai(Cortex Phellodendri Amurensis)with a largest dosage of 30 g per prescription.15The largest dosage of Zhimu(Rhizoma Anemarrhenae)was 82.8 g per prescription in Han and Tang Dynasties.16The dosage of Zhimu(Rhizoma Anemarrhenae)used by famous experts of Repub-lic of China was between 4 to 23 g.17The dosage of Dihuang(Radix Rehmanniae)in Han and Tang Dynasties was the largest(more than 41.4 g),and in a low level since Song Dynasty.18Our previous clinical observation indicated that efficacy occurred when the dosage of Huangbai(Cortex Phellodendri Amurensis),Zhimu(Rhizoma Anemarrhenae)and Dihuang(Radix Rehmanniae)added to 30 g.The dosage was still larger currently.Therefore,this observation selected two dosages lower than 30 g to research on dose-effect relationship.

12 Fauser BCJM.Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS).Hum Reprod 2004;81(1):19-25.

Figure 4 Comparison of acne scores of the HDG,MDG and LDG before and after treatment

HDG:high dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g];MDG:medium dosagegroup[consistedofZhimu(RhizomaAnemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g];LDG:low dosage group[consisted of Zhimu(RhizomaAnemarrhenae)10 g,Huangbai(CortexPhellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g].aP＜0.05 as compared with the datum before treatment;bP＜0.01 as compared with the datum before treatment.

This observation indicated that MZBDD had efficacy of reducing serum testosterone of PCOS and efficacy increased with the increasing of dosage.The efficacy of HDG were best with the largest amplitude in the decreasing of serum T followed by MDG.The acne scores of HDG obviously lower than that of LDG.It indicated that MZBDD had dose-effect relationship in treatment of PCOS hyperandrogenism.

该研究基于1954—2010年江西省宜春市袁州区油茶花期47类气象指标和油茶单产数据，采用逐步回归方法和相关分析，构建了袁州区基于花期气象条件的油茶产量模型，筛选出油茶花期关键气象因子，并对其进行趋势分析，得到以下结论：

Figure 5 Comparison of BBT biphasic rate among of the HDG,MDG and LDG

HDG:high dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g];MDG:medium dosagegroup[consistedofZhimu(RhizomaAnemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g];LDG:low dosage group[consisted of Zhimu(RhizomaAnemarrhenae)10 g,Huangbai(CortexPhellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g].BBT:basal body temperatures;HDG:high dosage group;MDG:medium dosage group;LDG:low dosage group.

Figure 6 Comparison of ALT and AST among the four groups

A:HDG:high dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)30 g,Huangbai(Cortex Phellodendri Amurensis)30 g,Dihuang(Radix Rehmanniae)30 g];MDG:medium dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)20 g,Huangbai(Cortex Phellodendri Amurensis)20 g,Dihuang(Radix Rehmanniae)20 g];LDG:low dosage group[consisted of Zhimu(Rhizoma Anemarrhenae)10 g,Huangbai(Cortex Phellodendri Amurensis)10 g,Dihuang(Radix Rehmanniae)10 g].NCG:normal control group;serum ALT;B:serum AST.ALT:alanine aminotransferase;AST:aspartate aminotransferase;HDG:high dosage group;MDG:medium dosage group;LDG:low dosage group;NCG:normal control group.

Parts of the patients could recover spontaneous ovulation after serum T reduced.Serum FSH concentration reduced,E2and P increased and BBT showed biphasic after ovulation.The observation showed that there were some patients developed biphasic BBT in all of the three groups.There were no obvious differences in the BBT biphasic rates among the three groups.Serum FSH concentration of all the three groups had reduced trend and both serum E2and P concentration had increased trend after treatment.The results demonstrated that parts of patients of all the three groups had spontaneous ovulation after treatment.This research wasn't suitable for study the effect of MZBDD on recovering spontaneous ovulation of PCOS because of the short treatment time.But it could show that MZBDD didn't inhibit follicular development and ovulation while reducing serum T.In that respect,MZBDD had obvious advantages compared with oral contraceptive pills which had the effect on reducing hyperandrogenism.

Without placebo-controlled,blind method and fixed prescription were the inadequate points of this study.For further deep study,a stricter research design should be made to elaborate the dose-effect relationship and the mechanism of Zhibaidihuang decoction on treating PCOS hyperandrogenism.

REFERENCE

根据土壤供肥能力和作物需肥量来进行科学施肥，不但能提高作物的产量，而且能提高产品的品质。比如能通过此方法能提高产品中矿物质的含量；提高蔬菜、瓜果中维生素C及其他营养物质含量；提高棉花衣分、绒长和铃重，减少蕾、铃脱落。

1 Azziz R,Woods K S,Reyna R,et al.The prevalence and features of the polycystic ovary syndrome in an unselected population.JClin EndocrinolMetab 2004,89(6):2745-2749.

Demographic characteristics including age,marriage,history of drug usage was asked.All the HA patients were drawn fasting vein blood in the morning of 2-4 d of the menstrual cycle(progesterone withdrawal bleeding)before treatment and the next day after treatment.The outcomes included:(a)serum total T(T),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),estradiol(E2),progesterone(P);(b)acne score(rosenfield);(c)Basal body temperature(BBT),calculating BBT biphasic rate;(d)alanine aminotransferase(ALT),aspartate aminotransferase(AST).And for the else,T,E2,FSH,LH,PRL,AST,AST were determined only before treatment.

3 Azziz R,Carmina E,Dewailly D,et al.Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome:an androgen excess society guideline.J Clin Endocrinol Metab 2006;91:4237-4245.

4 Guo LL,Ye GD.Clinical analysis of 292 women of childbearing age with polycystic ovary syndrome in Zunyi region.ZhongGuoFuYouBaoJian2011;26(17):2580-2583.

5 Yu AQ,Li XR.Clinical observation of smoothing liver and purging fire medicine in treating 22 cases of polycystic ovary syndrome.Zhong Yi Yao Dao Bao 2009;15(12):17-19.

6 Tao LL,Zhang YZ,Sang X,Zeng L,Yu AQ,Chen LF.Effects of modified longdan Xiegan decoction on hyperandrogenism in patients with polycystic ovary syndrome of stagnant Fire in gan channel type.Zhong Guo Zhong Xi Yi Jie He Za Zhi 2006;26(9):838-841.

7 Ma MH,Wang XD.The application of method regulating kidney and clearing lung in the treatment of 26 cases with hyperandro-genism caused byPCOS.Nanjing Zhong Yi Yao Da Xue Xue Bao 2010;26(4):311-312.

8 Cui XF,Mo XY.Clinical observation of tonifying kidney and dissolve phlegm medicine in treating 50 cases of polycystic ovary syndrome with high testosterone.Jilin Zhong Yi Yao 2012;32(4):378-379.

9 Liu XM,Liu R,Ai L,et al.Research of polycystic ovary syndrome TCM syndrome based on serum abnormal hormones.Huan Qiu Zhong Yi Yao 2013;6(1):12-15.

试验首先采用Excel 2013软件进行初步整理，然后采用SPSS16.0单因素方差分析模块进行单因素方差分析，邓肯氏法进行多重比较。差异显著水平判断标准为P＜0.05。

10 Liu XM,Liu R,Xu X,Ma L,Wen S.Clinical observation of tonifying kidney-Yinand Fire-clearing medicine in treating 30 cases of polycystic ovary syndrome with high testosterone.ShiJieZhongYiYao2015;10(7):1013-1016.

13 Luo YK.Gynecology of Traditional Chinese Medicine.Shanghai:Shanghai Science and Technology Press,1986:40-69.

PCOS is a heterogeneous disorder with clinical characteristic.The hyperandogenism patients might have single increased serum testosterone concentration,or accompanied by increased serum luteinizing hormone concentration or hyper-insulin and insulin resistant.The patients who have increased serum testosterone concentration accompanied by hyper-insulin and insulin resistant are common in overweight and obesity patients,which belongs to the range of TCM"stuffy and fully sensation in middle energizer and interior heat"type,which isn't suitable for using Zhibaidihuang decoction.BMI≥24 kg/m2was cut-off for overweight according to＜Working Group on Obesity in China.Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults(extract)＞19.This observation excluded the patients whose BMI were over 24.

这一夜，梨花要了三次，高木给了三次；不，不，是高木要了三次，梨花给了三次。俩人都累坏了，最后静静地躺在灯光里。梨花不久就入睡了。高木也困极了，但他怎么也睡不着；他侧过身，静静地望着梨花白玉般的身体。她面如桃红，呼吸若兰；水蜜桃般的乳房上，四周乳晕隆起，乳头翘翘的。高木偷偷地俯下身去，用嘴轻轻地含住一只乳头。梨花咿呀了一声，吓得高木赶紧松嘴，梨花随即又呼呼睡去，在梦里喃喃而语：“回去吧！回去……”

11 Tong XL,Liao YZ,Lian M,et al.Some thoughts about the key points in the research of the dose-response relationship.Huan Qiu Zhong Yi Yao 2012;5(6):401-404.

There was no significant difference in serum T among the HDG,MDG and LDG before treatment(P=0.221)(Figure 2).Compared with before treatment,serum T concentration of both MDG and HDG were significantly lower after treatment(P=0.039,P=0.000),while there were no differences in LDG(P=0.829)(Figure 2).Serum T was lower in 40.7%cases in LDG after treatment,while 70.8%in MDG and 86.7%in HDG,respectively(P=0.048,P=0.006)(Figure 2).There were significantly differences in serum T after treatment among the three groups(P=0.896),of which both MDG and HDG were lower than that of LDG(P=0.031,P=0.001)(Figure 2).There were also significant differences in the decreasing amount of serum T among the three groups after treatment(P=0.022).HDG of the largest amplitude was significantly higher than that of LDG(P＜0.001).While compared with NCG,there was significantly difference in serum T concentration before treatment of HDG,MDG and LDG(allP=0.000)(Figure 2).

学校可以开展针对任务型教学法的观课、评课比赛。通过学习其他教师的教学优势，提高自身素质，定期检查教案，评比教案。教师需要反复收集材料，处理材料，设定任务，精算时间。这是一个班级成功的关键。备课是一项艰苦的心理活动，教师必须在有限的时间内计划好所有的步骤，准备应对紧急情况的策略。与没有任何准备的纯教学相比，它有不同的效果。在任务的设计上，一个课时的任务数量要根据教学内容来设置。它不能太多或太少。Skehan曾说过，“任务型教学的核心是让学生通过学习语言完成任务。”[1]任务设置必须有针对性。通过完成这项任务，学生将掌握一些技能。老师应该掌握这项工作的困难程度。

15 Chen CR,Li BG,Zhang L,et al.Review on the dosage of Cortex Phellodendri used in clinics in the past dynasties.Zhong Yi Za Zhi 2014;55(13):1142-1145.

16 Song J,Zhang L,Chen CR,et al.Review on the dosage ofRhizoma Anemarrhenaeused in clinics in the past dynasties.Shanghai Zhong Yi Yao Za Zhi 2014;48(10):74-78.

17 Xiang CH,Fan X,Jiang YW,et al.Research ofRhizoma Anemarrhenaedosage base on clinical medication by master of TCM in the republic of China.Hubei Zhong Yi Za Zhi 2012;34(2):3-4.

18 Fu YL,Zhang L,Wang BF.Review on the dosage ofRadix Rehmanniaeused in clinics in the past dynasties.Zhong Yi Za Zhi 2014;55(23):2039-2042.

采用SPSS 19.0统计学软件对数据进行处理，计数资料例数（n）、百分数（%）表示，采用x2检验，计量资料以“x± s”表示，采用t检验，以P＜0.05为差异有统计学意义。

19 Working Group on Obesity in China.Guidelines for prevention and control of overweight and obesity in Chinese adults(extract).ACTA Nutrimenta Sinica 2004;26(1):1-4.