Current status of outcome reporting in randomized controlled trials of traditional Chinese medicine for mammary gland hyperplasia: A systematic review

Objective:To assess outcome indicators in clinical trials and provide a reference for establishing a core outcome set to treat hyperplasia of mammary gland(HMG)with traditional Chinese medicine(TCM).Methods:Eight online databases were searched from their inception to December 31,2022,to assess outcomes reported in randomized controlled trials(RCTs)of HMG treated with TCM.The quality of the included studies was assessed according to the Cochrane Risk of Bias Assessment Tool.All outcomes were extracted,classified,and described.Results:A total of 8249 articles were initially retrieved.Of these,70 articles were eligible and involved 10618 participants with HMG.A total of 17 outcome indicators with a frequency of 271 times were involved and were collected according to six outcome domains.Conclusions:The core outcomes of RCTs of HMG treated with TCM are large and divergent.There are problems in evaluation standards,primary and secondary outcomes,TCM characteristic indicators,long-term prognosis,and standardization of reporting.It is recommended to strengthen the trial design and actively construct the core outcome sets with TCM characteristics for HMG.

Thinking Path and Method for Establishing the Disease/ Chinese Medicine Syndrome Conjugated Pattern of a Mammary Hyperplasia Animal Model

Mammary hyperplasia （MHP） is the most commonly encountered mammary disease in women at the child-bearing stage. Especially, atypical hyperplasia which belongs to the precancerous category, is the disease for class Ⅰ prevention of breast cancer. Therefore, advancing the clinical efficacy of MHP treatment is of critical importance. Chinese medicine （CM） and drugs show a peculiar effect in this field; the clinical or experimental researches concerning MHP treatment by CM compounds or patent drugs have been increasing gradually in recent years, but the thinking paths and methods for establishing the MHP animal model are divergent. Particularly, the disease/CM syndrome conjugated model （D/S model） has rarely been studied. For this reason, the pathogenetic mechanism, the establishment of an animal disease model, as well as the thinking paths and methods for establishing the D/S model of MHP are discussed and summarized preliminarily in this paper by the authors. This could provide a new way of thinking and method for creating the MHP model in modern medicine.

Effect of Lirukang Oral Liquid(利乳康口服液) on Neurotransmitters and Estrogen in Rats with Hyperplasia of Mammary Gland

Objective: To investigate the effects of Lirukang oral liquid (LRK, 利乳康口服液) on release of neurotransmitter in rats with hyperplasia of mammary glands (HMG) and to explore its mechanism. Methods: Sixty rats were divided into six groups, the normal control group, the model control group, the large dosage (3.6g/kg) and the small dosage (1.8g/kg ) LRK groups, the Ruzengning (乳增宁, RZN, 2.5g/kg) group and the tamoxifen (TAM, 5mg/kg) group, 10 in each group. Except those in the normal control group, all the animals were made into rat model of HMG by intraperitoneal injection of estradiol benzoate. Levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in hypothalamus and mammary gland in rats were detected by fluorescence luminosity assay, and level of prolactin (PRL) in serum was detected by radioimmunoassay. Results: In the model group, the level of DA reduced significantly ( P<0. 01), and 5-HT and PRL increased obviously ( P<0.01). Compared with the model group, the LRK groups of both dosages and the TAM group had their level of DA significantly increased (P<0. 01), and level of 5-HT significantly decreased ( P<0.01). The serum PRL in both LRK groups was significantly decreased ( P<0. 01). No obvious changes in DA, 5-HT and PRL were found in the RZN group. Conclusion: LRK and TAM have similar effects in regulating the release of neurotransmitter in hypothalamus and mammary gland and serum content of estrogen in the animal models of HMG.

Differential Acupuncture Treatment of Hyperplasia of Mammary Glands

Hyperplasia of mammary glands is a common disease in the middle-aged women, and it is a precancerous lesion of mammary glands. For many years, the author has used Rugen (ST 18) of the Stomach Meridian of Foot-Yangming as the main point withcertain auxiliary points chosen on basis of the differentiation types to treat the disease and obtained satisfactory therapeutic effects. A report follows. ……

Core acupoints of acupuncture for hyperplasia of mammary gland: a network analysis

Backgroud:Clinical studies on acupuncture treatment of hyperplasia of mammary gland(HMG)have proved its effectiveness,but most studies have paid little attention to acupoints prescription and acupoint compatibility.The clinical prescription is not identical,the curative effect also has the difference.Therefore,through data mining and network analysis,this study explored the core acupoints and the compatibility law of acupoints in acupuncture treatment of HMG.Methods:To search and select qualified literature according to inclusion and exclusion criteria for relevant clinical research literature on acupuncture treatment of HMG in CNKI,VIP database,WanFang database and PubMed,etc.Then extract relevant information and establish a database.Using the method of statistical and complex network analysis,this paper studies the core acupoints and the law of acupoint compatibility.Results:A total of 104 Chinese literatures and 0 English literatures were included and 106 acupuncture prescriptions were extracted.The core acupoints in the treatment of HMG are Danzhong(CV 17),Wuyi(ST 15),Zusanli(ST 36),Jianjing(GB 21).Danzhong(CV 17)and Zusanli(ST 36),Danzhong(CV 17)and Wuyi(ST 15),Jianjing(GB 21)and Tianzong(SI 11),Jianjing(GB 21)and Wuyi(ST 15)have the highest correlation degree.The method of acupoint matching mainly consists of local-remote acupoints,upper-lower acupoints and front-rear acupoints.Conclusion:The results of a network analysis substantially accord with the general rules of acupuncture theories in traditional Chinese medicine,able to reflect the points-selection principles and features in acupuncture treatment of HMG and provide evidence for the acupoints selection in the treatment of HMG in acupuncture clinic.

THE EXPRESSION OF APOPTOSIS RELATED GENES IN THE PROCESS OF CANCERATION OF ATYPICAL HYPERPLASIA OF MAMMARY DUCT

Objective： To investigate the expression of apoptosis related genes p53 and bcl-2 in atypical hyperplasia of mammary duct and the relationship between the gene expression and oncogenesis of breast. Methods： mRNA of apoptosis related gene p53 and bcl-2 were detected by in situ hybridization in 44 cases of atypical ductal hyperplasia. p53 protein expression was detected by immunohistochemistry. The data were compared with those of 6 cases of benign hyperplasia and 26 cases of breast carcinoma. Results： The expression of p53 mRNA was 66.7% in benign hyperplasia, 40% in atypical ductal hyperplasia （55.6% in mild, 41.7% in medium, 26.1% in severe） and 19.2% in carcinoma （of which 21.4% were intraductal carcinoma and 16.7% were invasive）. The expression of p53 protein was negative in benign hyperplasia, 24% in atypical hyperplasia （mild 11.1%, medium 25%, severe 34.8%）, 38.5% in carcinoma （intraductal carcinoma 35.7%, invasive ductal carcinoma 41.7%）. The expression of bcl-2 was negative in benign hyperplasia, 78.6% in intraductal carcinoma, 83.3% in invasive ductal carcinoma. Conclusion： Loss and mutation of p53 gene and excessive expression bcl-2 mRNA were detected in severe atypical ductal hyperplasia.

Rupi Sanjie capsule plus surgical operation for the treatment of hyperplasia nodule of mammary gland:A meta-analysis and trial sequential analysis

Objective:To evaluate the efficacy and safety of Rupi Sanjie(RPSJ)capsule plus the conventional surgical operation for treatment of hyperplasia nodule of mammary gland.Methods:A meta-analysis was conducted on randomized controlled trials(RCT)related to RPSJ capsule plus surgical operation in the treatment of hyperplasia nodule of mammary gland.The methodological quality of eligible RCTs was assessed according to the criteria from the Cochrane Handbook for Systematic Reviews of Interventions.RevMan5.3 and Stata14.0 were used for data analyses.Trial sequential analysis was performed to estimate the sample size of systematic review base on TSA software v0.9.Results:Twenty-two RCTs were totally included in this study,involving 2135 patients.The result showed the clinical recurrence rate of RPSJ capsule plus surgical treatment group was significantly lower than surgical treatment alone group(RR:0.25,95%CI[0.17,0.37],P<0.01).The clinical cure rate and total effective rate were higher in RPSJ capsule plus surgical treatment group than the conventional surgical treatment group(RR:1.63,95%CI[1.46,1.82],P<0.01);(RR:1.29,95%CI[1.22,1.37],P<0.01).Application of RPSJ capsule decreased the occurrence of adverse events including nausea,vomiting,irregular menstruation,constipation,dizziness,and headache etc.(RR:0.90,95%CI[0.54,1.49],P=0.68).The results of trial sequential analysis demonstrated that the current available data did not reach the expected value.Conclusion:RPSJ capsule plus the conventional surgical treatment was more effective in reducing the clinical recurrence rate,and improving the total clinical effective rate and clinical cure rate,with a decrease in the occurrence of adverse events.

Clinical Observation on Treatment of Hyperplasia of Mammary Gland by Lirukang Granule (利乳康颗粒)

Objective： To explore the efficacy and mechanism of Lirukang Granule （利乳康颗粒, LRKG） in treating hyperplasia of mammary gland （HMG）. Methods： One hundred patients with HMG were randomly assigned to two groups, 50 in each group. The patients in the treated group were orally administered with LRKG thrice a day, one package each time, and those in the control group were given orally Rukuaixiao Tablet （乳块消, RKX） thrice a day, 4 tablets each time. The therapeutic course for both groups was 4 months. The clinical efficacy, pain alleviating rate, as well as changes of local sign and symptom scores were observed before and after treatment. The changes of serum estradiol （E2）, progesterone （P）, testosterone （T）, follicle stimulating hormone （FSH）, luteinizing hormone （LH） and prolactin （PRL） in some randomly selected patients （24 patients in the treated group and 24 in the control group） before and after treatment were measured with radioimmunoassay. Results： The total clinical efficacy in the treated group was superior to that in the control group, significant difference was shown between the two groups （P〈 0.01）. The cure-effective rate and total effective rate in the treated group were 70.0%and 88.0% respectively, significantly higher than those in the control group （38.0% and 64.0%） respectively （P〈 0.01）, and the pain alleviating rate in the treated group was also significantly higher in the former than that in the latter （88.0% vs 64.0%, P 〈 0.05）. Moreover, the treated group showed obvious superiority in improving the patients＇ symptom and sign scores （P 〈 0.01）, and abnormalities of gonadal hormone as compared with the respective items in the control group （P〈0.01）. Conclusion： LRKG has good efficacy in the treatment of HMG, and its mechanism may be related to the regulation on endocrine and immune function.

Clinical Observation on Treatment of Mammary Gland Hyperplasia by Acupoint Injection Combined with Ion-Introduction of Chinese Herbal Medicine

Objective: To observe the effect of combined therapy of acupoint Injection and Chinese herbal medicine ion-introduction in treating mammary gland hyperplasia (MGH). Methods: Eighty-six patients of MGH were treated with the combined therapy and compared with a control group treated with other Chinese or western drugs. Results: Therapeutic effect evaluated after 3 courses of treatment showed that the effect of combined therapy was superior to that of the control groups treated by Xiaoyao Pill, Rupixiao tablet, Asparagine tablet and combined therapy of vitamin E + oryzanol + vitamin B6. Conclusion: Combined treatment of acupoint injection and ion-introduction of Chinese herbal medicine is an effective treatment for mammary gland hypertrophy.

电针联合刮痧治疗乳腺增生病临床疗效观察

Objective:To evaluate the clinical therapeutic effect on mammary hyperplasia of electroacupuncture(EA)combined with scraping therapy.Methods:A total of 54 patients with mammary hyperplasia were adopted EA combined with scraping therapy.Two groups of acupoints were selected.One group is Wuyi(屋翳ST15),Danzhong(膻中CV17)and Hegu(合谷LI4),EA was applied to these acupoints.Anothor group is Tianzong(天宗SI11),Jianjing(肩井GB21)and Ganshu(肝俞BL18),scraping therapy was applied to these points.Other acupoints were accompanied to.Ten times of treatments were as one course,at the interval of 1 week among the treatment courses.Totally,3 courses were required.Before and after treatment,the score of the symptoms of mammary hyperplasia,the grade and score of breast lumps and the levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)were evaluated in the patients.Results:Compared with the scores before treatment,the scores of the symptoms of mammary hyperplasia and breast lumps were all reduced in the patients,indicating the statistical significant differences(all P<0.05).Compared with the levels before treatment,the levels of FSH,LH and E2 were all reduced in the patients,indicating the statistical significant differences(all P<0.05).The total effective rate was 92.59%after treatment.Conclusion:Electroacupuncture combined with scraping therapy achieves a satisfactory clinical effect on mammary hyperplasia.