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BACKGROUND: Prunella vulgaris L., a medicinal and edible homologous plant, is often used to treat conditions such as breast hyperplasia, thyroid enlargement and lymphatic tuberculosis. Research has demonstrated that it is particularly effective in the treatment of mammary gland hyperplasia (MGH). However, the material basis and mechanism of its efficacy are still unclear. RESULTS: Our results showed that in rats with MGH, polysaccharide from Prunella vulgaris L. (PVP) led to a reduction in the levels of estradiol, prolactin and malondialdehyde, while simultaneously increasing the concentrations of progesterone (P), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD) and catalase (CAT) in the serum. In addition, results obtained from 16S rRNA sequencing demonstrated that PVP had the capacity to increase the richness and diversity of the intestinal microbiota in MGH rats, as well as modify the structure of the microbiota. Correlation analysis revealed that the levels of P, SOD, MnSOD and CAT were positively associated with Allobaculum, Romboutsia, Faecalibaculum and Clostridium, while negatively correlated with Turicibacter. CONCLUSIONS: The mechanism of PVP in treating MGH might be through inhibiting the phosphorylation of the AKT‐FOXO3a signaling pathway and then activating the expression of downstream antioxidant enzymes, such as MnSOD and CAT. At the same time, PVP could restore intestinal flora homeostasis in rats with MGH by regulating the flora changes of Allobaculum, Romboutsia, Clostridium and Faecalibaculum, thereby reducing oxidative stress in rats with MGH. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Objective: To establish a preparation method of Atractylodes macrocephala Koidz polysaccharide (AMP) sulfate with anti-hyperplasia of mammary. Methods: AMP were sulfated by sulfated method, and the optimal conditions for the sulfated modification were determined by response surface methodology. The structures of AMP and SAMP were initially analyzed by infrared spectroscopy (IR) and High-Performance Gel Chromatography (HPGPC). The anti-oxidative activity in vitro of polysaccharide was investigated by testing the DPPH, ABTS+, OH free radical scavenging ability of AMP and SAMP. Rat model of mammary gland hyperplasia was established by intramuscular injection of estradiol benzoate and progesterone. The rats weight and breast diameter were recorded and the pathological organization form of mammary gland of rats were observed. Results: The optimum preparation conditions were as follows: Ratio of conditions of volume ratio of sulfuric acid and n-butanol 2:1, reaction temperature −4 ℃, reaction time 21 min. The degree of substitution of SAMP was 0.59±0.00391. The HPGPC results showed the relative molecular weights for AMP and SAMP were 2719 and 33524 Da, respectively. The IR spectra showed that SAMP had characteristic absorption peaks of S=O and C-O-S appeared near 833 and 1226 cm−1, indicating that the sulfated was successful. When the sample concentration was 0.5 mg/mL, the DPPH, ABTS+, OH free radical scavenging activities of SAMP were 54.91% , 38.21%, and 42.23%, respectively. Compared with the model group, the diameter of the nipples of the rats in the SAMP group decreased (P

Background: The pathogenesis of hyperplasia of mammary glands (HMG) is a complex process, involving multiple links and systems within the body. Current clinical research indicates that traditional Chinese medicine (TCM) demonstrates a significant therapeutic effect in treating HMG. Single herbs or herbal pairs (two herbs) are the basic units of preventing and treating HMG. It is of great significance to explore the mechanism of single herbs or herbal pairs in treating HMG for clarifying the mechanism of preventing HMG with TCM. Purpose: This study aimed to review the literature, summarize the known mechanisms of single herbs and herbal pair therapy for treating hyperplasia of mammary glands (HMG), and elucidate the relevant substances involved within and outside the body during these treatments. Study design: In this study, the action mechanism of single herbs or herbal pairs in treating HMG was selected as the research object. English articles were mainly selected and Chinese articles were supplemented. We conducted a literature search in PubMed, CNKI, WanFang Database, etc，including full-text studies published between January 1992 and December 31, 2022. The primary literature was carefully screened, and the mechanism of action was explored by logical analysis. Methods: We conducted a literature review focusing on basic studies that explored the mechanisms underlying the effects of herbal treatments for mammary gland hyperplasia. The literature search was performed in PubMed, CNKI, and WanFang Database, covering full-text articles published from January 1992 to 31 December 2022, using various keywords (e.g., hyperplasia of mammary glands, single herb, herbal pair, effect, mechanism, inclusion criteria). Exclusion criteria were also set. We employed methods such as literature measurement, literature research, and content analysis to logically analyze, induce, and deduce the findings of the collected literature. Results: This review reveals that several distinct mechanisms contribute to the beneficial effects of single herbs or herbal pairs on the recovery of mammary gland hyperplasia. Regarding hormone levels, Chinese herbs can decrease hormones such as Estradiol(E2) and Prolactin(PRL), increase Progesterone(P) levels, balance the E2/P ratio, reduce the expression of sex hormone receptors, and lessen the self-sensitivity of breast tissue under the influence of E2. Histologically, Chinese herbs can inhibit breast neovascularization and alleviate blood viscosity. At the cellular level, Chinese herbs can modulate the expression of apoptosis genes and proteins, decrease cell proliferation activity, and ultimately inhibit or even reverse breast hyperplasia. From a pharmacological perspective, Chinese herbs exhibit analgesic, anti-inflammatory, antioxidant, and immune-regulating properties. Conclusion: The evidence in this review demonstrates the effectiveness of single herbs or herbal pairs in preventing and treating mammary gland hyperplasia, with precise underlying mechanisms.

In female Wistar rats, mammary gland hyperplasia (MGH) was modeled according to a modified protocol involving estrogen-progesterone induction and taking into account the duration of the estrous cycle of this animal species. MGH was induced over four 7-day cycles; each cycle included subcutaneous administration of 17β-estradiol (0.5 mg/kg) for 4 days, injection of progesterone (5 mg/kg) on day 5, then 2 days without injections. In females with MGH, a significant increase in the height and diameter of the nipples of the mammary glands was recorded, two types of changes were observed in the gland tissue: tubuloalveolar and lobuloalveolar hyperplasia. The study confirmed the development of MGH in rats by a modified method. [ABSTRACT FROM AUTHOR]

Background: A microneedle patch loaded with Atractylodes macrocephala Rhizoma water extract was prepared for the treatment of mammary gland hyperplasia. To explore the relationship between Mammary gland hyperplasia and intestinal flora. Materials and methods: Preparation of the microneedle patch by micromolding method, the prescription of the microneedle was optimized by the Box-Behnken Design response surface test, and the micro-morphology, penetration, toughness, and brittleness were investigated. In vitro release of drug-loaded microneedles was measured by diffusion cell method. The rat model of mammary gland hyperplasia was prepared by the combination of estradiol benzoate-progesterone, and the microneedle patch of Atractylodes macrocephala Rhizoma aqueous extract was used for intervention treatment. The change of levels in E2, P, and PRL in rat serum was determined. The intestinal contents of rats were collected and the changes in intestinal flora in MGH rats were analyzed by 16s rRNA high-throughput sequencing. Results: The optimized microneedle formula is a PVA concentration of 6.0%, HA concentration of 15.5%, and PVPK30 concentration of 16.0%. The prepared microneedle tip loaded with Atractylodes macrocephala Rhizoma aqueous extract has complete, sharp, and no bubbles and the needle rate of the microneedle array is in the range of 95%~100%. The bending rate of the microneedle is about 12.7%, and it has good flexibility, and the microneedle can puncture 4 layers of ParafilmⓇ membrane smoothly, and the puncture rate is more than 96%. The in vitro release of the microneedle was characterized by rapid release. The results of animal experiments showed that Atractylodes macrocephala Rhizoma aqueous extract microneedle patch could significantly reduce the E2 level, significantly reduce the PRL level, and significantly increase the P level. At the same time, it can regulate the abundance and diversity of intestinal flora in MGH rats, improve the intestinal flora disorder caused by mammary gland hyperplasia, and balance the community structure. Conclusion: The prepared microneedle containing Atractylodes macrocephala Rhizoma aqueous extract has good toughness and brittle strength, can penetrate the skin and enter the dermis, and effectively deliver drugs to play a role in the treatment of mammary gland hyperplasia. [ABSTRACT FROM AUTHOR]

Background: Network meta-analysis is used as a data synthesizer, incorporating direct and indirect evidence about treatments in a series of randomized control trials. Objective: To evaluate the comparative efficacy of various Kidney nourishments for treating mammary gland hyperplasia (HMG). Methods: We performed a network meta-analysis to combine direct and indirect data to investigate the efficiency of drug therapies, which were evaluated in relevant randomized control trials for HMG. Results: Thirty-seven eligible studies were included in this meta-analysis. A total of 4002 patients were included, in whom 21 therapeutic interventions were used. BieJiaJain Pill showed the highest efficacy in total efficiency, whereas Tamoxifen was the least effective. YanLuRuKang Capsule/Pill, AnRu Decoction showed higher efficacy in modulating Estradiol, whereas Tamoxifen and RuPiSanJie Capsule were lower effective. YanLuRuKang Capsule/Pill, RuKangShu Capsule, AnRu Decoction showed higher efficacy in narrowing lump, whereas RuKang Pill/Capsule, RuPiXiao Granules/Pill, RuPiSanJie Capsule were lower effective. YiShenShuGan Capsule/Decoction, WenYangXiaoPi Compound, TiaoChongGuBen Decoctiom showed higher efficacy in reducing painscore, whereas Tamoxifen, RuPiXiao Granules/Pill, RuPiSanJie Capsule were lower effective. XiaoYao Pill, RuPiSanJie Capsule showed higher efficacy in modulating progesterone, whereas WenYangXiaoPi Compound, TiaoChongGuBen Decoctiom were poorly effective. YiShenShuGan Capsule/Decoction, WenYangXiaoPi Compound, AnRu Decoction showed higher efficacy in modulating prolactin, whereas Tamoxifen, RuPiXiao Granules/Pill, RuPiSanJie Capsule were lower effective. Conclusion: In this study, the efficacy of oral Chinese herbal compounds in treating mammary glands hyperplasia was analyzed systematically and objectively, which provided a theoretical basis for clinical medication and was helpful for clinicians to make the best choice of medication. Due to the limitations of the selected literature, the conclusions of this study still need to be validated by high-quality clinical trial studies.

BackgroundIn recent years, mammary gland hyperplasia (MGH) has been considered to be one of the diseases caused by endocrine disorders. It has been shown that diseases caused by endocrine disorders can be treated by regulating intestinal microbial. As a commonly used medicine in clinical practice, Atractylodes Macrocephala Rhizoma has good functions in regulating intestinal homeostasis. Therefore, this paper studied the effect of Atractylodes Macrocephala Rhizoma polysaccharide (AMP) on the intestinal flora of MGH rats, providing a new idea for polysaccharide treatment of MGH.Materials and methodsEighteen female SD rats were selected and randomly divided into three groups: blank control group (Con), model control group (Mod), and AMP group, six rats in each group. MGH rat models were established by estradiol-progesterone combination and treated with AMP gastric infusion. The levels of E2, P, and PRL in the serum of rats were measured, the intestinal contents were collected, and 16s rRNA high- throughput sequencing technology was analyzed the changes of intestinal flora in the MGH rats.ResultsAMP has good therapeutic effects on MGH rats, decreasing estradiol (E2) and prolactin (PRL) levels and increasing progesterone (P) levels; at the same time, it can regulate the abundance and diversity of intestinal flora of MGH rats, improve the disorder of intestinal flora caused by MGH, and change the community structure, increase the abundance of beneficial flora, and decrease the abundance of pathogenic flora.ConclusionAMP can improve the intestinal microbiological environment of MGH rats, maintain the microecological balance of intestinal microbial, and improve MGH symptoms.

Objective To investigate the effect of rubbing therapy with Chinese herbal medicine ointment on pain relief in patients with hyperplasia of mammary gland. Methods Totally 40 patients suffering from pain caused by mammary gland hyperplasia were randomly divided into the control group and treatment group, with 20 cases in each group. All patients received oral administration of Chinese herbal medicine, and those in the treatment group were given rubbing therapy with Chinese herbal medicine ointment. The Numerical Rating Scale was used to evaluate the degree of pain before treatment and 14 days after treatment. Results After 14 days intervention, better pain relief was noted in the treatment group than that in the control group, with a significant difference (P＜0. 05). Conclusion The rubbing therapy with Chinese herbal medicine ointment is an easy-to-operate, safe and effective treatment on pain relief in patients with mammary gland hyperplasia. (目的 探讨乳腺中药膏摩治疗乳腺增生病疼痛的效果。方法 40例乳腺增生病患者随机分为对照组和治疗组, 各20例。对照组实施口服中药治疗, 治疗组在口服中药基础上增加乳腺中药膏摩治疗。采用数字评分法(NRS)评估患者疼痛程度, 评价干预效果。结果 干预14 d后, 疼痛干预效果治疗组优于对照组, 差异有统计学意义(P＜0. 05)。结论 中药膏摩能有效缓解乳腺增生病患者疼痛程度, 且操作简单、安全。)

As reported that the usage of estrogen and/or progesterone increases the risk of mammary gland hyperplasia (MGH) with conflicting results. Therefore, we conducted a meta-analysis to higher elucidate the relationship between hormones and MGH. PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Wan-fang database were searched for studies until April 28, 2021. Nine related studies were included in the present meta-analysis. We found that the usage of estrogen and/or progesterone had a significant association with increasing the risk of MGH (RR = 1.56, 95% CI: 1.13–2.15, p =.000). The subgroup results showed that the risk of MGH increased in the Mix population (RR = 1.72, CI: 1.58–1.88, p <.001) but no significant difference in the Asian population. Meanwhile, as for using estrogen plus progesterone (EPP) and postmenopausal women the risk of MGH, respectively, increased (RR = 1.74, CI: 1.22–2.47, p =.002) and (RR = 1.75, CI: 1.24–2.47, p =.001) but no significant different for using estrogen alone and premenopausal women. This study findings indicated that using estrogen and/or progesterone might increase the risk of MGH in premenopausal and postmenopausal women. [ABSTRACT FROM AUTHOR]

Hong-Hua-Xiao-Yao Tablet (HHXYT) is a traditional Chinese medicine (TCM) formula that has been approved for the treatment of mammary gland hyperplasia (MGH), but its mechanism of action is unclear. In this study, a strategy that integrated metabolomics and network pharmacology was applied to systemically reveal the mechanism of HHXYT in the treatment of MGH. Our pharmacodynamic study indicated that the proliferation of mammary gland was inhibited in rats, and serum-level disorder of estradiol and progesterone was reversed after HHXYT treatment. 54 compounds absorbed in rat plasma were identified after administration of HHXYT. The serum metabolome revealed 58 endogenous differential metabolites, of which 31% were steroid lipids metabolites, with steroid hormone biosynthesis being the most significant metabolic module. 7 targets, 6 herbs, and 17 ingredients were found to play key roles in HHXYT's treatment of MGH. 3 of the 7 key targets (CYP11A1, HSD3B2, and CYP17A1) were directly involved in androgen synthesis, while 2 targets (AR and ESR1) were receptors for the direct action of androgens and estrogens. Molecular docking was utilized to confirm the bindings between the 5 targets and their corresponding compounds. In an in vitro test, HHXYT (50 µg/ml) and its ingredient formononetin (3.2, 6.3, and 12.5 µM) were found to significantly reduce the increase of testosterone level induced by dexamethasone (10 µM) in thecal cells. In summary, this study illustrated that the mechanism of HHXYT's treatment of MGH was to regulate hormone disorder. HHXYT could reduce estrogen-stimulated hyperplasia by inhibiting the production of its precursor androgen. [ABSTRACT FROM AUTHOR]

Hong-Hua-Xiao-Yao Tablet (HHXYT) is a traditional Chinese medicine (TCM) formula that has been approved for the treatment of mammary gland hyperplasia (MGH), but its mechanism of action is unclear. In this study, a strategy that integrated metabolomics and network pharmacology was applied to systemically reveal the mechanism of HHXYT in the treatment of MGH. Our pharmacodynamic study indicated that the proliferation of mammary gland was inhibited in rats, and serum-level disorder of estradiol and progesterone was reversed after HHXYT treatment. 54 compounds absorbed in rat plasma were identified after administration of HHXYT. The serum metabolome revealed 58 endogenous differential metabolites, of which 31% were steroid lipids metabolites, with steroid hormone biosynthesis being the most significant metabolic module. 7 targets, 6 herbs, and 17 ingredients were found to play key roles in HHXYT’s treatment of MGH. 3 of the 7 key targets (CYP11A1, HSD3B2, and CYP17A1) were directly involved in androgen synthesis, while 2 targets (AR and ESR1) were receptors for the direct action of androgens and estrogens. Molecular docking was utilized to confirm the bindings between the 5 targets and their corresponding compounds. In an in vitro test, HHXYT (50 µg/ml) and its ingredient formononetin (3.2, 6.3, and 12.5 µM) were found to significantly reduce the increase of testosterone level induced by dexamethasone (10 µM) in thecal cells. In summary, this study illustrated that the mechanism of HHXYT’s treatment of MGH was to regulate hormone disorder. HHXYT could reduce estrogen-stimulated hyperplasia by inhibiting the production of its precursor androgen.

To study the efficacy of breast nodule lysis (BNL) for the treatment of mammary gland hyperplasia (MGH). A total of 304 patients with MGH and breast pain were randomly divided into a BNL group and an oral tamoxifen (OT) group. In the BNL group (n = 156), patients were treated with BNL technique once a day for 7 consecutive days. BNL is a novel technique developed by our department, by which breast nodules can be released and breast duct can be cleared via external force and manipulation. In the OT group (n = 148), patients took oral tamoxifen 10 mg once a day for 15 consecutive days beginning 5 days after termination of the menstrual period for 3 menstrual cycles. The McGill Pain Questionnaire (MPQ) score, number and size of breast nodules pre- and post-treatment, efficacy, time to response, total treatment expenses, recurrence rate, and side effects were compared across groups. The MPQ score was significantly better in the BNL than the OT on day 7, and the total effective rate (86.54%) was significantly higher in the BNL than the OT (43.92%) on day 15. The number and size of breast nodules were decreased in the BNL compared with the OT 15 days, 3 months, and 6 months after treatment. The total treatment expenses were higher in the BNL than the OT. The recurrence rate within 6 months was lower in the BNL than the OT. There was no difference in side effects (nausea, vomiting, diarrhea, or dizziness) across groups. BNL can effectively alleviate pain and reduce the number and size of nodules with quick effect and a low recurrence rate, making it an enticing treatment for MGH. [ABSTRACT FROM AUTHOR]

XiaoJin Capsule (XJC) is a classic Traditional Chinese Medicine formula for clinical treatment of thyroid nodules, mammary gland hyperplasia and breast cancer. For the specification and rational application of XJC in the future, an accurate and specific LC–MS/MS method was developed and validated for quantitative determination of five components in rat plasma after oral administration of XJC. The collected plasma samples were extracted by protein precipitation with methanol–acetonitrile (1:3, v/v) mixture solvent and separated on a C18 column using a gradient elution system. Mass spectrometry was performed on a triple quadrupole mass spectrometer, and samples were detected in positive ionization and multiple reactions monitoring mode. The method was properly validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves showed good linearity (r2 > 0.9910) over their concentration ranges. The intra‐ and inter‐day precisions (RSD) were within 11.0%, and the LLOQ was 0.1, 0.2, 0.5, 7.5 and 7.5 ng/ml for aconine, songorine, neoline, 3‐acetyl‐11‐keto‐β‐boswellic acid and 11‐keto‐β‐boswellic acid, respectively. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. This established method was successfully applied to a pharmacokinetics study of five compounds after oral administration of XJC to normal and mammary gland hyperplasia model rats. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis., Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis., Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score., Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Mammary gland hyperplasia (MGH) is very common, especially among young and middle-aged women. New diagnostics and biomarkers for MGH are needed for rational clinical management and precision medicine. We report, in this study, new findings using a glycomics approach, with a focus on immunoglobulin G (IgG) N-glycosylation. A cross-sectional study was conducted in a community-based population sample in Beijing, China. A total of 387 participants 40–65 years of age were enrolled in this study, including 194 women with MGH (cases) and 193 women who had no MGH (controls). IgG N-glycans were characterized in the serum by ultra-performance liquid chromatography. The levels of the glycan peaks (GPs) GP2, GP5, GP6, and GP7 were lower in the MGH group compared with the control group, whereas GP14 was significantly higher in the MGH group (p < 0.05). A predictive model using GP5, GP21, and age was established and a receiver operating characteristic curve analysis was performed. The sensitivity and specificity of the model for MGH was 61.3% and 63.2%, respectively, likely owing to receptor mechanisms and/or inflammation regulation. To the best of our knowledge, this is the first study reporting on an association between IgG N-glycosylation and MGH. We suggest person-to-person variations in IgG N-glycans and their combination with multiomics biomarker strategies offer a promising avenue to identify novel diagnostics and individuals at increased risk of MGH. [ABSTRACT FROM AUTHOR]

The agouti (Dasyprocta leporina) is a neotropical rodent that is utilized for its meat by hunters as well as wildlife farmers. There is a dearth of information on infectious diseases that affect these animals. At present, there has been no recording in the literature on diseases of mammary tissue in these animals. This case reported on the abnormal mammary enlargement of a four year old female agouti post-partum. Blood, milk and tissue samples were taken for diagnostics to determine the cause of disease. Histological samples confirmed the swelling of the mammary gland as a diffuse mammary hyperplasia. Hematological values obtained were within the reference range of agoutis reared in captivity. The milk samples that were taken cultured Staphylococcus spp. in one mammary gland (left inguinal). The cultured bacteria in the milk samples confirmed this animal had mastitis. The bacterial cultured (Staphylococcus aureus) was sensitive to tetracyclines, ampicillin, trivetrin and ceftiofur. To the authors' knowledge, this is the first record in the literature on mastitis in the agouti. Thus, this information will add to the knowledge of diseases in captive reared agoutis. [ABSTRACT FROM AUTHOR]

The agouti (Dasyprocta leporina) is a neotropical rodent that is utilized for its meat by hunters as well as wildlife farmers. There is a dearth of information on infectious diseases that affect these animals. At present, there has been no recording in the literature on diseases of mammary tissue in these animals. This case reported on the abnormal mammary enlargement of a four year old female agouti post-partum. Blood, milk and tissue samples were taken for diagnostics to determine the cause of disease. Histological samples confirmed the swelling of the mammary gland as a diffuse mammary hyperplasia. Hematological values obtained were within the reference range of agoutis reared in captivity. The milk samples that were taken cultured Staphylococcus spp. in one mammary gland (left inguinal). The cultured bacteria in the milk samples confirmed this animal had mastitis. The bacterial cultured (Staphylococcus aureus) was sensitive to tetracyclines, ampicillin, trivetrin and ceftiofur. To the authors’ knowledge, this is the first record in the literature on mastitis in the agouti. Thus, this information will add to the knowledge of diseases in captive reared agoutis.

Mammary gland hyperplasia (MGH) is a pathological condition that affects the majority of women at the child-bearing stage. The hormone and endocrinal therapy are typically used to treat MGH. Nevertheless, there are still some certain side effects accompanied with the benefits, which negatively affect the life quality of patients. Therefore, plant-derived agents that are effective against MGH development and with fewer side effects should be developed. The aim of this study was to investigate the protective effects and underlying mechanism of total saponins of Phytolaccae (TSP) against MGH in vivo. The results showed that treatment with TSP could significantly correct the disorder of serum sex hormones levels in rats with MGH, and eliminate the formation of MGH. Moreover, TSP significantly protected estrogen and progesterone-induced MGH histological changes, inhibited the swelling of the nipple, and improved the organ coefficient of uterus in rats with MGH. Mechanistically, TSP treatment not only effectively suppressed the mRNA and protein expression of ERα and PR in mammary gland, but also simultaneously up-regulated ERβ expression, and thus blocked sex hormones from interacting with their receptors. TSP treatment markedly suppressed mammary phosphorylation levels of ERK1/2, as well as reduced the mRNA and protein overexpression of VEGF and bFGF in mammary of rats. In addition, TSP treatment substantially down-regulated the expression of Bcl-2 and Ki-67, as well as elevated the expression of Bax. These findings indicated that TSP could potentially be used for effective treatment of MGH.

As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09–4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28–0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72–2.71; P < 0.00001) and decrease the size of breast lump (MD: −0.67; 95% CI: −0.86 to −0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH.

Background: The pathogenesis of hyperplasia of mammary glands (HMG) is a complex process, involving multiple links and systems within the body. Current clinical research indicates that traditional Chinese medicine (TCM) demonstrates a significant therapeutic effect in treating HMG. Single herbs or herbal pairs (two herbs) are the basic units of preventing and treating HMG. It is of great significance to explore the mechanism of single herbs or herbal pairs in treating HMG for clarifying the mechanism of preventing HMG with TCM., Purpose: This study aimed to review the literature, summarize the known mechanisms of single herbs and herbal pair therapy for treating hyperplasia of mammary glands (HMG), and elucidate the relevant substances involved within and outside the body during these treatments., Study Design: In this study, the action mechanism of single herbs or herbal pairs in treating HMG was selected as the research object. English articles were mainly selected and Chinese articles were supplemented. We conducted a literature search in PubMed, CNKI, WanFang Database, etc，including full-text studies published between January 1992 and December 31, 2022. The primary literature was carefully screened, and the mechanism of action was explored by logical analysis., Methods: We conducted a literature review focusing on basic studies that explored the mechanisms underlying the effects of herbal treatments for mammary gland hyperplasia. The literature search was performed in PubMed, CNKI, and WanFang Database, covering full-text articles published from January 1992 to 31 December 2022, using various keywords (e.g., hyperplasia of mammary glands, single herb, herbal pair, effect, mechanism, inclusion criteria). Exclusion criteria were also set. We employed methods such as literature measurement, literature research, and content analysis to logically analyze, induce, and deduce the findings of the collected literature., Results: This review reveals that several distinct mechanisms contribute to the beneficial effects of single herbs or herbal pairs on the recovery of mammary gland hyperplasia. Regarding hormone levels, Chinese herbs can decrease hormones such as Estradiol(E2) and Prolactin(PRL), increase Progesterone(P) levels, balance the E2/P ratio, reduce the expression of sex hormone receptors, and lessen the self-sensitivity of breast tissue under the influence of E2. Histologically, Chinese herbs can inhibit breast neovascularization and alleviate blood viscosity. At the cellular level, Chinese herbs can modulate the expression of apoptosis genes and proteins, decrease cell proliferation activity, and ultimately inhibit or even reverse breast hyperplasia. From a pharmacological perspective, Chinese herbs exhibit analgesic, anti-inflammatory, antioxidant, and immune-regulating properties., Conclusion: The evidence in this review demonstrates the effectiveness of single herbs or herbal pairs in preventing and treating mammary gland hyperplasia, with precise underlying mechanisms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

As a common disorder that accounts for over 70%of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09-4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28-0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72-2.71; P < 0.00001) and decrease the size of breast lump (MD: -0.67; 95% CI: -0.86 to -0.49; P < 0.00001) to a greater extent, whichmight provide a possible explanation for the pharmacodynamicmechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH. [ABSTRACT FROM AUTHOR]

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Mammary gland hyperplasia (MGH) occurs with high frequency among middle-aged women and is closely related to breast cancer. The treatment of this disease has become a research hotspot. Many patients with MGH are worried about the potential side effects of the synthetic drugs they are on. Thus, they seek alternative therapy, such as traditional Chinese medicine (TCM). In recent years, along with the Chinese herbs and its active ingredients, TCM compounds have been widely accepted and implemented in the treatment of MGH, whose mechanism hitherto is not completely clear. In this paper, we elaborate the mechanism of TCM in the treatment of MGH from the perspectives of sexual hormone levels, the expression of ER and PR, hemorheology, free radical activity and lipid peroxidation, VEGF and BFGF, cell proliferation activities, anti-apoptosis gene BcL-2, promoting apoptosis gene Bax, ERK, and tumor suppressor gene. In conclusion, TCM appears to be promising for MGH treatment. This paper will provide an overview of the mechanism of TCM in the treatment of MGH. In the near term, a better understanding of TCM will be achieved through comprehensive studies of its molecular mechanism. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals) and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation.

Background: A microneedle patch loaded with Atractylodes macrocephala Rhizoma water extract was prepared for the treatment of mammary gland hyperplasia. To explore the relationship between Mammary gland hyperplasia and intestinal flora., Materials and Methods: Preparation of the microneedle patch by micromolding method, the prescription of the microneedle was optimized by the Box-Behnken Design response surface test, and the micro-morphology, penetration, toughness, and brittleness were investigated. In vitro release of drug-loaded microneedles was measured by diffusion cell method. The rat model of mammary gland hyperplasia was prepared by the combination of estradiol benzoate-progesterone, and the microneedle patch of Atractylodes macrocephala Rhizoma aqueous extract was used for intervention treatment. The change of levels in E 2 , P, and PRL in rat serum was determined. The intestinal contents of rats were collected and the changes in intestinal flora in MGH rats were analyzed by 16s rRNA high-throughput sequencing., Results: The optimized microneedle formula is a PVA concentration of 6.0%, HA concentration of 15.5%, and PVPK30 concentration of 16.0%. The prepared microneedle tip loaded with Atractylodes macrocephala Rhizoma aqueous extract has complete, sharp, and no bubbles and the needle rate of the microneedle array is in the range of 95%~100%. The bending rate of the microneedle is about 12.7%, and it has good flexibility, and the microneedle can puncture 4 layers of ParafilmⓇ membrane smoothly, and the puncture rate is more than 96%. The in vitro release of the microneedle was characterized by rapid release. The results of animal experiments showed that Atractylodes macrocephala Rhizoma aqueous extract microneedle patch could significantly reduce the E 2 level, significantly reduce the PRL level, and significantly increase the P level. At the same time, it can regulate the abundance and diversity of intestinal flora in MGH rats, improve the intestinal flora disorder caused by mammary gland hyperplasia, and balance the community structure., Conclusion: The prepared microneedle containing Atractylodes macrocephala Rhizoma aqueous extract has good toughness and brittle strength, can penetrate the skin and enter the dermis, and effectively deliver drugs to play a role in the treatment of mammary gland hyperplasia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ping, Gao, Li, Wang, Wang, Li, Qiu, Zhang, Tu, Tian and Zhao.)

Background: In recent years, mammary gland hyperplasia (MGH) has been considered to be one of the diseases caused by endocrine disorders. It has been shown that diseases caused by endocrine disorders can be treated by regulating intestinal microbial. As a commonly used medicine in clinical practice, Atractylodes Macrocephala Rhizoma has good functions in regulating intestinal homeostasis. Therefore, this paper studied the effect of Atractylodes Macrocephala Rhizoma polysaccharide (AMP) on the intestinal flora of MGH rats, providing a new idea for polysaccharide treatment of MGH., Materials and Methods: Eighteen female SD rats were selected and randomly divided into three groups: blank control group (Con), model control group (Mod), and AMP group, six rats in each group. MGH rat models were established by estradiol-progesterone combination and treated with AMP gastric infusion. The levels of E 2 , P, and PRL in the serum of rats were measured, the intestinal contents were collected, and 16s rRNA high- throughput sequencing technology was analyzed the changes of intestinal flora in the MGH rats., Results: AMP has good therapeutic effects on MGH rats, decreasing estradiol (E 2 ) and prolactin (PRL) levels and increasing progesterone (P) levels; at the same time, it can regulate the abundance and diversity of intestinal flora of MGH rats, improve the disorder of intestinal flora caused by MGH, and change the community structure, increase the abundance of beneficial flora, and decrease the abundance of pathogenic flora., Conclusion: AMP can improve the intestinal microbiological environment of MGH rats, maintain the microecological balance of intestinal microbial, and improve MGH symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ping, Li, Wang and Zhao.)

Objective: To explore the effacacy of acupuncture in regulating pituitary-ovarian axis hormones on mammary gland hyperplasia (MGH) in the rat model induced by exogenous estradiol (E2). Methods: Female non pregnant SD rats were used. All rats were randomly divided into control group (group A), model group (group B) and acupuncture group (group C). Estradiol benzoate was injected intramuscularly in the lateral hindlimb of the rats every other day to induce models. Two groups of acupoints were alternatively punctured (group A was Tianzong (SI11), Ganshu (BL18), Zusanli (ST36), group B was Wuyi (ST15), Hegu (LI4), Tanzhong (RN17)). On the 61st day of the experiment, the eyeball blood of rats was extracted and serum was centrifuged for detection. Results: The E2, FSH and PRL levels of rats in group C were significantly lower than that of model group, while concentration of P, T and LH secreted by the ovary was significantly higher than that in group B (P < 0.01). Levels of E2, FSH and PRL in the model group were significantly higher than that in group A (P < 0.01), P, T and LH were significantly lower than group A (P < 0.01); the ratio of E2 with P, T, FSH, PRL in the model group, respectively, was significantly different with that in group A (P < 0.01). E2 and P were negatively correlated in group B and C; E2 was positively correlated with T in group A, but negatively related in group B, and had no correlation in group C; There was no correlation between FSH and E2 in group A and group B, E2 and FSH was negatively correlated in group C; E2 and PRL was positively correlated in group A and group C. Conclusion: Acupuncture can decrease the levels of E2, PRL and FSH in model rats with MGH, improve the level of P, LH and T secreted by the ovary; Acupuncture can regulate the relativity of sex hormones in rat models with MGH and correct the disorder of sexual hormone level in diseased rats. [ABSTRACT FROM AUTHOR]

In the present study, a rat model of breast hyperplasia was established via the administration of estradiol benzoate and progesterone. Subsequent changes associated with breast hyperplasia were then investigated by measuring the diameter and height of the nipples and by staining breast tissue with hematoxylin and eosin. The proliferation and apoptosis of hyperplastic cells in the breast tissue were then determined by analyzing the expression of proliferating cell nuclear antigen (PCNA) and cleaved‑caspase‑3 by immunohistochemistry and TUNEL staining. We also determined the expression of proteins associated with the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway by western blotting. Melatonin treatment led to a significant reduction in the degree of breast hyperplasia (P<0.05), a significant reduction in PCNA, a significant increase in the level of apoptosis (P<0.05), a significant increase in PTEN (P<0.05), and a significant reduction in AKT/p‑AKT (P<0.05). Furthermore, melatonin significantly decreased the aggravation of breast hyperplasia induced by application of a PTEN inhibitor. Melatonin reduced the degree of breast hyperplasia, reduced the proliferation of hyperplastic breast tissue cells, and promoted cell apoptosis in hyperplastic tissue. These effects were achieved by the specific regulation of proteins in the PTEN/PI3K/AKT axis.

Objective: To analyze the acupoint combination regularities and application characteristics of core acupoints in acupuncture-moxibustion treatment of mammary gland hyperplasia (MGH) by using complex network technology, so as to provide reliable evidence for clinical selection of acupoints and treatment ideas., Methods: The articles related to acupuncture treatment of MGH published from January of 1981 to May of 2020 were collected from databases as China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), Chinese Journal of Science and Technology of VIP (VIP), PubMed, the Excerpta Medica Database (EMBASE), Cochrane Library, and Web of Science and Ovid database (OVID) according to the set inclusion and exclusion criteria of the present paper and by using keywords of "mammary gland hyperplasia", "mastalgia" or "fibrocystic breast change", "breast cystic hyperplasia ", etc. plus "acupuncture", "moxibustion", etc. Then, a correlative database model was established by using SPSS Modeler 18.0 to analyze their association regularities, followed by conducting a complex network analysis with Gephi 0.9.2 software., Results: A total of 312 eligible articles containing 343 acupoint prescriptions and 113 acupoints were collected. The total frequency of use of the 113 acupoints was 1 998. The association regularity analysis showed a top relativity between Danzhong(CV17) and Zusanli(ST36). The analysis of the complex network topology revealed that CV17, Qimen(LR14), Sanyinjiao(SP6), Taichong(LR3), ST36, Jianjing(GB21), Rugen(ST18), Wuyi(ST15), Neiguan(PC6), Ashi-points, Fenglong (SP40), Guanyuan(CV4), Taixi(KI3), Tianzong(SI11), Ganshu (BL18), and Hegu(LI14) are the core acupoints for treatment of MGH. The principle for composing acupoint prescriptions is mainly the combination of acupoints on the left and right sides, the upper and lower parts, front and back parts of the body, respectively, and those of the outer and inner meridians, and those of the same name meridians and Zangfu-organ syndrome differentiation. The needle-insertion direction is mostly toward the focus., Conclusion: The composition of acupoint prescriptions for treating MGH with acupuncture and moxibustion is mainly based on the combination of specific acupoints among which the confluent acupoints are most frequently used, followed by the combination of acupoints distributing at the chest, back, upper and lower limbs, and the local acupoints.

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 B. Conclusion: Combined treatment of acupoint injection and ion-introduction of Chinese herbal medicine is an effective treatment for mammary gland hypertrophy. [ABSTRACT FROM AUTHOR]