Clinical Efficacy of Dingkundan in Treatment of Ovulatory Disorder Infertility Based on Real-world / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Dingkundan in the treatment of ovulation disorder infertility based on the real world and provide reliable evidence-based medical support for clinical practice. MethodClinical diagnosis and treatment data of patients with ovulation disorder infertility in the real world were collected through the Medroad Cloud system. Patients were grouped according to their real-world treatments， and the total effective rate， ovulation rate per cycle， number of days of follicle development， gonadotropin （Gn） dosage， levels of mature follicle-related hormones， endometrial thickness and classification， pregnancy rate per cycle， clinical pregnancy rate， ectopic pregnancy rate， and early pregnancy loss rate were observed. ResultA total of 207 patients were included， and the most common traditional Chinese medicine （TCM） syndrome in the entire population was liver depression and kidney deficiency. The patients were divided into a Chinese medicine group （Dingkundan， 60 cases）， a western medicine group （ovulation induction， 51 cases）， and a combination group （Dingkundan + ovulation induction， 96 cases）. The combination group（98.96%，95/96） had the highest total effective rate， which was statistically significant when compared with the Chinese medicine group（88.33%，53/60） （χ2=8.328， P<0.05）. The mature follicle estradiol （E2） and luteinizing hormone （LH） levels were the highest in the combination group， and there were statistically significant differences when compared with the western medicine group （P<0.01）. The endometrial thickness was higher in the Chinese medicine group and the combination group than in the western medicine group （P<0.01）. The proportion of type A endometrium was highest in the combination group（85.90%，201/234）， and there was a statistically significant difference when compared with the western medicine group（73.81%，93/126） （χ2=7.993， P<0.01）. The clinical pregnancy rate was 60.42%（58/96） in the combination group， which was higher than 36.67%（22/60） in the Chinese medicine group （χ2=8.336， P<0.01） and 39.22%（20/51） in the western medicine group （χ2=6.011， P<0.05）. Compared with the western medicine group， the combination group showed a favorable trend in total effective rate， ovulation rate per cycle， number of days of follicle development， Gn dosage， pregnancy rate per cycle， ectopic pregnancy rate， and early pregnancy loss rate， but the differences were not statistically significant. ConclusionIn real-world clinical practice， the combination of Dingkundan with ovulation induction can increase endometrial thickness， improve the proportion of type A endometrium， enhance egg quality， and increase the clinical pregnancy rate in patients with ovulation disorder infertility. This approach deserves further clinical research and application.

Efficacy Evaluation of Dingkundan in Treatment of Female Infertility： A Systematic Review Based on Randomized Controlled Trials / 中国实验方剂学杂志

This study systematically evaluated the effectiveness and safety of Dingkundan combined with conventional western medicine in the treatment of female infertility. Four Chinese databases，three English databases， and two clinical trial registration platforms were retrieved from inception to April 2021. Two researchers independently carried out literature screening，data extraction，risk assessment of bias，and grading of evidence quality. RevMan 5.4.1 was used for data analysis. A total of 216 research articles were retrieved and 21 randomized controlled trials （RCTs） were included，involving 2 172 cases. The risks of bias in the included RCTs were high. As unraveled by Meta-analysis results， Dingkundan combined with western medicine for ovulation stimulation was superior to western medicine for ovulation stimulation alone in improving pregnancy rate and progesterone level ［relative risk（RR）pregnancy rate=1.67，95% confidence interval（CI）（1.44，1.93）；standardized mean difference （SMD）progesterone=1.21，95% CI（0.82，1.60）］. Dingkundan combined with western medicine for improving the endometrium was superior to western medicine for improving the endometrium alone in improving the pregnancy rate ［RRpregnancy rate=1.35，95% CI（1.23，1.48）］. Dingkundan combined with clomiphene was more effective than clomiphene alone in regulating endometrial thickness and reducing follicle-stimulating hormone and estradiol levels ［MDendometrial thickness=3.34，95% CI（3.27，3.41）， MDfollicle-stimulating hormone=-0.42，95% CI（-0.65，-0.19）， MDestradiol=-4.33，95% CI （-8.18，-0.48）］. Dingkundan combined with letrozole was superior to letrozole alone in increasing the follicle-stimulating hormone level and reducing the estradiol level ［MD follicle-stimulating hormone=1.14，95% CI（0.49，1.78）， MDestradiol =-33.65，95% CI（-59.13，-8.17）］. The single-study results showed that Dingkundan combined with conventional western medicine had certain advantages in regulating endometrial thickness，reducing follicle-stimulating hormone，luteinizing hormone，and estradiol levels，and increasing progesterone levels. The Grading of Recommendations， Assessment， Development， and Evaluation（GRADE）system was used for the evaluation of outcome indicators. The results showed that the quality of the evidence was graded moderate or low. Based on the existing evidence，Dingkundan combined with western medicine for infertility treatment had certain advantages in increasing the pregnancy rate， improving endometrial thickness， regulating hormone levels， and reducing adverse reactions. However，affected by the quality of the included trials，the results may have limitations，and high-quality RCTs are needed for verification in the future.

Effect of Dingkundan in Adjuvant Treatment of Patients with Radiotherapy and Chemotherapy After Endometrial Carcinoma Operation / 中国实验方剂学杂志

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （<italic>P</italic><0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （<italic>P</italic><0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （<italic>P</italic><0.01）， and scores of three symptom dimensions were lower than those in control group （<italic>P</italic><0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （<italic>P</italic><0.01）， and CD8⁺ was lower than those in the control group （<italic>P</italic><0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-<italic>β</italic>₁ were lower than those in the control group （<italic>P</italic><0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （<italic>χ</italic>²=4.572， <italic>P</italic><0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

Effect of Dingkundan on Sex Hormone and Follicle Count in Mice of Tripterygium Wilfordii Polyglycosides Induced Diminished Ovarian Reserve / 中国实验方剂学杂志

Objective:To establish a mouse model of diminished ovarian reserve （DOR） induced by tripterygium wilfordii polyglycosides （TWP）， and to explore the therapeutic effect of Dingkundan （DKD） on DOR， so as to provide scientific basis for its clinical application. Method:The 60 female Blab/c mice with regular estrous cycle were randomly divided into blank group， model group， low，medium and high-dose DKD group， DKD group and estradiol valerate group， with 10 mice in each group. Except the blank group， the other groups were given 40 mg·kg-1 TWP suspension. Meantime，low，medium and high-dose DKD group were given 1.64，3.28，6.56 g·kg-1 DKD suspension respectively， and estradiol valerate group was given 0.15 mg·kg-1 estradiol valerate suspension by gastric lavage once a day for 30 days. The general condition， body weight， estrous cycle and gonad index of mice were observed， serum follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and estradiol （E2） were determined by radioimmunoassay， ovarian morphology and follicle count were observed by hematoxylin-eosin staining （HE） staining. Result:Compared with the blank group， most of the mice in model group had disordered estrous cycle， uterine and ovarian indexes decreased （P<0.05）， serum FSH increased （P<0.05）， LH was on an upward trajectory， E2 was on a downward trend， and the number of growth follicles and corpus luteum decreased and the number of atresia follicles increased（P<0.05）. Compared with the model group， half of the mice in DKD group resumed regular estrous cycle， however， the estrous cycles of mice in estradiol valerate group were stagnated during estrous period. In medium-dose， high-dose DKD group and estradiol valerate group， the uterine and ovarian indexes of the mice were increased， the serum FSH value decreased （P<0.05） and serum LH was on a downward trend， high-dose DKD group and estradiol valerate group increased the levels of serum E2 （P<0.05）. In DKD group， the number of growth follicles and corpus luteum were increased and the number of atresia follicles were reduced （P<0.05）， with the best effect at medium dosage. And in estradiol valerate group， the number of primitive follicles， sinusoidal follicles and corpus luteum were increased （P<0.05）， but the number of atresia follicles had no difference to the model group. Conclusion:DKD can improve serum sex hormones， promote follicular development and reduce follicular atresia， which can play a therapeutic role in the treatment of DOR.

Curative efficacy of Oryzanol combine with Dingkundan in treatment of perimenopausal period and its effects on endocrine improvement / 中国生化药物杂志

Objective To study Curative efficacy of Oryzanol combine with Dingkundan in treatment of perimenopausal period and its effects on endocrine improvement.Methods 90 patients of perimenopausal period who received therapy from March 2014 to March 2015 in our hospital were selected as research objects.According to draw method divided into the experimental group(n=45)and the control group(n=45).Two groups of patients were psychological support.The control group was treated with Oryzanol, each 10 mg, 3 times a day.while the experimental group was on the control group, treated with Dingkundan, 1 pills each time, 2 times a day, in the morning and evening.Then Serum estradiol(E2), Follicle stimulating hormone(FSH), Luteinizing hormone(LH)level, upset hot sweating, insomnia, irritability, hung up improve time, Kupperman score, clinical efficacy of two groups were compared.Results The E2 level in experimental group was significantly higher than the control group[(72.51±5.30)pg/mL vs.(66.80±4.75)pg/mL](P<0.05), FSH、LH level was significantly lower than the control group[(21.36±1.05)mIU/ml vs.(26.09±1.89)mIU/mL,(24.34±1.01)mIU/mL vs.(20.61±1.50)mIU/mL](P<0.05);upset hot sweating, insomnia, irritability, hung up improve time was significantly lower than the control group[(11.21±2.35)d vs.(20.05±5.07)d,(12.78±2.09)d vs.(18.32±4.13)d,(11.30±2.10)d vs.(20.16±5.02)d,(10.20±2.76)d vs.(16.58±4.03)d](P<0.05);Kupperman score was significantly lower than the control group[(4.32±1.09)score vs.(12.76±3.16)score](P<0.05);total effective rate was significantly higher than the control group[93.33%(42/45)vs.75.67%(34/45)](P<0.05).Conclusion Oryzanol combine with Dingkundan is well for perimenopausal period,which can significantly improve endocrine disorders, promote its balance, improve estrogen.

Effects of DingKunDan on the endometriosis model rats / 安徽医科大学学报

We built rats model of endometriosis applying autologus endometrial transplants to compare the graft vol-ume of the modeling rats before and after dosing,serum tumor necrosis factor alpha(TNF-α)levels in rats,and the expressions of vascular endothelial cell growth factor(VEGF)in ectopic endometrium.To compare with the control group,the graft volume of DingKunDan group was reduced and the serum TNF-αlevel declined ,and also the ex-pression of VEGF in ectopic endometrium was reduced.Their differences were statistically significant (P <0.05). DingKunDan can inhibit the growth of ectopic endometrium in endometrosis model rats.The mechanism may be re-lated to the decrease of the serum TNF-αlevel and the VEGF expression.

Microscopic Identification of Dingkundan(Red Radix Ginseng,Radix Notoginseng,etc.) / 中成药

In this paper we present a study on the microscopic identification of Dingkundan.For this purpose,a total of 29 constitutive Chinese medicines in Dingkundan were all detected and the characters of every constitutive Chinese medicine for microscopic identification were briefly described.We also provide the microscopic character pictures attached.