Non-sentinel lymph node metastases risk factors in patients with breast cancer with one or two sentinel lymph node macro-metastases.

Approximately 59 % of patients with breast cancer with one or two sentinel lymph nodes (1-2 SLN) macrometastases do not benefit from axillary lymph node dissection (ALND), which may also incur morbidities. It is necessary to evaluate the association between various clinicopathological characteristics and non-sentinel lymph node metastases (non-SLNM) in patients with breast cancer with 1-2 SLN macrometastases, and determine whether they 1-2 should avoid ALND. Eight electronic literature databases (PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal, Wanfang, and Chinese Biomedical Literature) were searched from their inception to June 30, 2023, and two reviewers independently extracted the data and assessed the risk of bias. Association strength was summarized using odds ratios (OR) and 95 % confidence intervals (CI). Heterogeneity was accounted for using a subgroup analysis. Publication bias was evaluated using funnel plots and Egger's test. There were 25 studies with 8021 participants, and 27 potential risk factors were evaluated. The risk factors for non-SLNM in patients with 1-2 SLN macrometastatic breast cancer include the following: factors of primary tumor: multifocality (OR (95 % CI (2.63 (1.96, 3.54))), tumor size ≥ T2 (2.64 (2.22, 3.14)), tumor localization (upper outer quad) (2.06 (1.23, 3.43)), histopathological grade (G3) (2.45 (1.70, 3.52)), vascular invasion (VI) (2.60 (1.35, 4.98)), lymphovascular invasion (LVI) (2.87 (1.80, 4.56)), perineural invasion (PNI) (3.16 (1.18,8.43)). Factors of lymph nodes: method of SLNs detected (blue dye) (3.85 (1.54, 9.60)), SLN metastasis ratio ≥0.5 (2.79 (2.24, 3.48)), two positive SLNs (3.55, (2.08, 6.07)), zero negative SLN (3.72 (CI 2.50, 4.29)), extranodal extension (ENE) (4.69 (2.16, 10.18)). Molecular typing: Her-2 positive (2.08 (1.26, 3.43)), Her-2 over-expressing subtype (1.83 (1.22, 2.73)). Factors of examination/inspection: axillary lymph nodes (ALNs) positive on imaging (3.18 (1.68, 6.00)), cancer antigen 15-3 (CA15-3) (4.01 (2.33,6.89)), carcinoembryonic antigen (CEA) (2.13 (1.32-3.43)). This review identified the risk factors for non-SLNM in patients with 1-2 SLN macrometastatic breast cancer. However, additional studies are needed to confirm the above findings owing to the limited number and types of studies included.

Xiaozheng pill exerts an anti-mammary hyperplasia effect through Raf/ERK/ELK and HIF-1α/bFGF pathways.

Background and aim: The purpose of this study is to explore whether the Xiaozheng pill (XZP) has the effect of anti-hyperplasia of mammary glands (HMG) and to identify the related signaling pathways. Experimental procedure: We analyzed the effective chemical components of the XZP, as well as the key chemical components, key proteins, main biological processes, and pathways in the treatment of HMG; Secondly, the levels of Estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Progesterone (P), Raf/ERK/ELK and HIF-1α/bFGF pathways related proteins were detected; Finally, the effect of XZP on metabolites was analyzed by metabolomics. Results and conclusion: In this study, we identified key targets and pathways for XZP therapy of HMG, including EGFR, VEGFA, ER, and Ras signaling pathways. Animal experiments show that XZP can reduce the levels of E2, LH, and FSH and increase the expression of P in HMG mice. XZP can restore the normal structure of breast tissue and reduce ERα, ERß, and PR expression in breast tissue. In addition, metabolomics results show that XZP also regulates HMG metabolites, including HIF-1α and metabolic pathways. The Western blot results showed that XZP intervention can reduce the protein expression of p-Raf1, Raf1, p-ERK1/2, ERK1/2, ELK, HIF-1α, and bFGF in the breast tissue of HMG mice. XZP may eliminate abnormal breast hyperplasia through inhibition of apoptosis and angiogenesis, which may be linked with the regulation of the Raf/ERK/ELK and HIF-1α/bFGF signaling pathways in HMG mice. These results suggest that XZP treatment may be beneficial for the management of HMG.

Clinical Effectiveness and Safety of Chinese Herbal Medicine Compound Kushen Injection as an Add-On Treatment for Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the effect and safety of compound Kushen injection (CKI) as an add-on treatment on the treatment for breast cancer. METHODS: We searched eight major electronic databases from their inception to November 1, 2021, for randomized clinical trials (RCTs) comparing CKI plus chemotherapy with chemotherapy alone. Primary outcomes included objective response rate (ORR) and disease control rate (DCR), health-related quality of life (HRQoL), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse drug reactions (ADRs) and tumor marker level. We used Cochrane's RevMan 5.3 for data analysis. The GRADEpro was used to appraise the certainty of evidence. Trial sequential analysis (TSA) was applied to estimate the required sample size in a meta-analysis and test the robustness of the current results. RESULTS: Thirty RCTs with 2556 participants were totally included. CKI plus chemotherapy showed significant effects in increasing ORR (RR 1.30, 95%CI [1.18, 1.43], I 2 = 27%, n = 1694), increasing DCR (RR 1.21, 95%CI [1.15, 1.28], I 2 = 16%, n = 1627), increasing HRQol as measured by Karnofsky Performance Scale (KPS) score improvement rate (RR 1.42, 95% CI [1.26, 1.61], I 2 = 37%, n = 1172), increasing the PFS (MD 2.24 months, 95%CI [1.26, 3.22], n = 94) and the OS (MD 2.24 months, 95%CI [1.45, 3.43], n = 94), compared to chemotherapy alone. The results showed that CKI plus chemotherapy had a lower risk of ADRs than that of chemotherapy alone group. The certainty of evidence of the included trials was generally low to very low. TSA for ORR and KPS score improvement rate demonstrated that the current results reached a sufficient power regarding both numbers of trials and participants. CONCLUSIONS: Low certainty of evidence suggested that the combination of CKI and conventional chemotherapy appeared to improve ORR, DCR, and KPS score in breast cancer patients. Conclusions about PFS and OS could not be drawn due to lack of evidence. Additionally, CKI appeared to relieve the risk of ADRs in patients with breast cancer receiving chemotherapies. However, due to weak evidence, the findings should be further confirmed in large and rigorous trials.

The mechanism of action of Fangji Huangqi Decoction on epithelial-mesenchymal transition in breast cancer using high-throughput next-generation sequencing and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FHD) is widely used in traditional Chinese medicine (TCM). FHD has been hypothesized to inhibit the epithelial-mesenchymal transition (EMT) process, which may positively impact breast cancer prevention and treatment. However, its exact mechanism of action is still unknown. AIM OF THE STUDY: This study aimed to screen potential targets of FHD for the treatment of EMT in breast cancer through network pharmacology, and to verify their therapeutic effects in vitro experiments and high-throughput second-generation sequencing. MATERIALS AND METHODS: The data sets of effective components and targets of FHD were established through the Traditional Chinese Medicine Systems Pharmacology database. The GeneCards and OMIM databases were used to establish breast cancer-related target datasets, which were then matched with the TCM target data. The interaction between key target proteins was analyzed using the STRING database; the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify the associated biological processes and enriched signal pathways, respectively. The active ingredient disease target network was analyzed using Cytoscape. Finally, next generation sequencing was used to verify the related pathways of FHD intervention in EMT in breast cancer. High-content screening was used to identify the genes/pathways affected by FHD. MDA-MB-231 and HCC-1937 breast cancer cell lines were used to evaluate the impact of FHD on migration, invasion, and EMT. RESULTS: Eighty possible significant targets were identified for the treatment of breast cancer EMT with FHD; GO and KEGG were used to identify 173 cell biological processes associated with breast cancer (P < 0.05), including the NF-κB and PI3K-Akt signaling pathways. The high-throughput sequencing and network pharmacology results were highly consistent. The migration and invasion ability of MDA-MB-231 cells was reduced and their EMT status could be reversed by DSHR2 knockdown. The results of morphology and scratch assays showed that FHD could improve the EMT status of HCC-1973. CONCLUSIONS: This study provides more evidence to support the clinical application of FHD, which has reliable interventional effects on breast cancer EMT. Its therapeutic effects may involve a multi-target, multi-pathway, and multi-mechanism effect.

Risk factors for lactation mastitis in China: A systematic review and meta-analysis.

BACKGROUND: Lactation mastitis (LM) affects approximately 3% to 33% of postpartum women and the risk factors of LM have been extensively studied. However, some results in the literature reports are still not conclusive due to the complexity of LM etiology and variation in the populations. To provide nationally representative evidence of the well-accepted risk factors for LM in China, this study was aimed to systematically summary the risk factors for LM among Chinese women and to determine the effect size of individual risk factor. MATERIAL AND METHODS: Six major Chinses and English electronic literature databases (PubMed, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wan fang Database and China Science Technology Journal Database) were searched from their inception to December 5st, 2020. Two authors extracted data and assessed the quality of included trials, independently. The strength of the association was summarized using the odds ratio (OR) with 95% confidence intervals (CI). The population attributable risk (PAR) percent was calculated for significant risk factors. RESULTS: Fourteen studies involving 8032 participants were included. A total of 18 potential risk factors were eventually evaluated. Significant risk factors for LM included improper milking method (OR 6.79, 95%CI 3.45-13.34; PAR 59.14%), repeated milk stasis (OR 6.23, 95%CI 4.17-9.30; PAR 49.75%), the first six months postpartum (OR 5.11, 95%CI 2.66-9.82; PAR 65.93%), postpartum rest time less than 3 months (OR 4.71, 95%CI 3.92-5.65; PAR 56.95%), abnormal nipple or crater nipple (OR 3.94, 95%CI 2.34-6.63; PAR 42.05%), breast trauma (OR 3.07, 95%CI 2.17-4.33; PAR 15.98%), improper breastfeeding posture (OR 2.47, 95%CI 2.09-2.92; PAR 26.52%), postpartum prone sleeping position (OR 2.46, 95%CI 1.58-3.84; PAR 17.42%), little or no nipple cleaning (OR 2.05, 95%CI 1.58-2.65; PAR 24.73%), primipara (OR 1.73, 95%CI 1.25-2.41; PAR 32.62%), low education level (OR 1.63, 95%CI 1.09-2.43; PAR 23.29%), cesarean section (OR 1.51, 95%CI 1.26-1.81; PAR 18.61%), breast massage experience of non-medical staff (OR 1.51, 95%CI 1.25-1.82; PAR 15.31%) and postpartum mood disorders (OR 1.47, 95%CI 1.06-2.02; PAR 21.27%). CONCLUSIONS: This review specified several important risk factors for LM in China. In particular, the incidence of LM can be reduced by controlling some of the modifiable risk factors such as improper breastfeeding posture, improper milking method, repeated milk stasis, nipple cleaning, breast massage experience of non-medical staff and postpartum sleeping posture.

Horizontal Rotary Cutting Technique for Skin Injury Avoidance in Superficial Benign Breast Masses.

OBJECTIVE: This study aims to investigate the feasibility of the horizontal rotary-cut technique in the removal of superficial benign breast tumors with a ≤1.0 cm distance between the upper margin of the tumor and the skin. PATIENTS AND METHODS: A total of 69 patients with superficial benign breast tumors received horizontal rotary-cut surgery between July 2018 and June 2019 (horizontal group). The rotary cutter groove was in the true lateral position of the tumor and the ultrasonic probe was vertical to the rotary cutter groove. The patients were compared with 33 patients who underwent the traditional vertical rotary-cut surgery between July 2017 and June 2018 (traditional group) regarding the aspects of operation time, intraoperative bleeding volume, postoperative skin ecchymosis, skin damage, and tumor residue. The rotary cutter groove was directly below the tumor and the ultrasonic probe was parallel to the rotary cutter groove in the traditional vertical rotary-cut surgery. RESULTS: The operation time in the horizontal group was significantly shorter than in the traditional group (7.7 ± 1.1 minutes vs 9.5 ± 1.3 minutes, with t = -7.458 and p = 0.000) and there was significantly less skin damage in the horizontal group than in the traditional group (0 cases vs 3 cases, with p = 0.032). The differences in intraoperative bleeding and postoperative skin ecchymosis between the two groups were not statistically significant (6.0 ± 1.3 mL vs 6.5 ± 1.5 mL, with t = -1.853 and p = 0.067; 4 cases vs 2 cases, with χ 2 = 0.003 and p = 0.958). Ninety-seven patients attended follow-ups for 6-30 (16.5 ± 4.5) months. No residues or recurrences were observed under ultrasound reviews in either group. CONCLUSION: In superficial benign breast tumor removal, the horizontal rotary-cut breast technique can help avoid skin injury, shorten the operation time, and reduce tumor residue more effectively compared with the traditional vertical rotary-cut technique. It has certain popularization and application values.

[Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice].

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Chinese herbal medicine (Rupi Sanjie capsule) for the treatment of breast pain: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Breast pain is one of the most common breast disorders, affecting 41%-69% women in the clinical populations. Chinese herbal medicine (Rupi Sanjie, RPSJ) capsule has been recommended to be commonly used for breast pain in China. This review aimed to systematically collect latest evidence and critically evaluate the eff ;ectiveness and safety of RPSJ capsule for breast pain. METHODS: We searched 6 databases from their inception to June 1, 2020 for randomized clinical trials (RCTs) comparing RPSJ capsule with conventional drug therapies, placebo or no treatment. Primary outcomes were breast pain relief, reduction of breast mass and clinical cure rate. RESULTS: Seventeen RCTs were included in total, involving 2899 participants with breast pain. RPSJ capsule showed a significant effects in shortening duration of the breast pain (MD-6.51 days, 95%CI [-8.57, -4.45], n = 82, 1 trial), shortening the duration of breast mass (MD-5.17 days, 95%CI [-7.56, -2.78], n = 82, 1 trial), improving clinical cure rate (RR 1.55, 95% CI [1.21, 2.00], I² = 64%, n = 1398, 10 trials) and total effective rate (RR 1.08, 95% CI [1.03, 1.14], I² = 71%, n = 2170, 14 trials) compared to Tamoxifen (TAM). The meta-analysis showed that the incidence of total adverse events was higher in TAM group than the RPSJ capsule group (RR 0.30, 95%CI [0.21, 0.42], I² = 49%, n = 2122, 13 trials). CONCLUSIONS: RPSJ capsule appears to be a potentially effective in treating breast pain and seems generally safe for clinical application. However, this potential benefit is inconclusive due to generally weak evidence, and the findings should be further confirmed in large and rigorous trials.

Anticancer Activity of Tetrandrine by Inducing Apoptosis in Human Breast Cancer Cell Line MDA-MB-231 In Vivo.

Tetrandrine (TET) is an alkaloid extracted from a traditional Chinese medicinal plant. It exerts remarkable anticancer activity and induces apoptotic cell death in various human cancer cells. The present study aimed to investigate the effects of TET on the inhibition of tumor growth and the induction of apoptosis in MDA-MB-231 breast cancer in xenograft mice. Tumor weight and volume were measured. The histopathological changes in the tumor tissue were observed. Immunohistochemistry analysis of Bcl-2-associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) was carried out. The expression of apoptosis-associated genes and proteins, such as cysteine aspartic acid-specific protease-3 (Caspase-3), Survivin, Bax, Bcl-2, BH3-interacting domain death agonist (Bid), and poly ADP-ribose polymerase (PARP), was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. TET inhibited tumor growth and induced apoptosis in TNBC cell line MDA-MB-231. The mechanism underlying this effect might be mediated by TET-upregulated Caspase-3, Bax, and Bid and downregulated by Bcl-2, Survivin, and PARP. Taken together, this study supported the fact that TET is a promising therapeutic agent for the treatment of TNBC, thereby providing experimental evidence for its use in the treatment of breast cancer.

Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways.

OBJECTIVE: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis. METHODS: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 µmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-ß1 (TGF-ß1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-ß1, NF-κB and Hes1 (P<0.05 or P<0.01). CONCLUSION: Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

Evaluation of serum creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate in a Chinese population.

OBJECTIVE: This study aimed to evaluate the applicability of a selection of glomerular filtration rate (GFR) estimating equations based on serum creatinine (SCr) and serum cystatin C in a Chinese population. MATERIAL AND METHODS: Estimated GFR values from 10 equations were compared with reference GFR (rGFR) from the (99m)Tc-DTPA renal dynamic imaging method. The study enrolled 569 Chinese participants (41.5% women, 53.5 ± 16.9 years, range 19-92 years), with mean rGFR 74.80 ± 26.10 (range 9.8-146.8 ml/min/1.73 m(2)). RESULTS: Bland-Altman analysis illustrated that the 95% agreement limits of all the equations surpassed the acceptable tolerance (<60 ml/min/1.73 m(2)), of which the MacIsaac equation was the closest one, reaching 71.7 ml/min/1.73 m(2). Linear regression analysis also demonstrated a consistent result. When assessed in all participants, the accuracy of the six equations reached and exceeded the acceptable level (≥70%), of which the Shanghai and MacIsaac equations gained more accuracy than others. When compared in subgroups, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), MacIsaac and Cockcroft-Gault (CG) equations were optimal for rGFR stages ≥ 90 ml/min/1.73 m(2), 30-89 ml/min/1.73 m(2) and < 30 ml/min/1.73 m(2), respectively. CONCLUSION: The results demonstrated that further improvement is needed for the selected 10 equations. Not all the cystatin C equations were superior to SCr equations. They have their own applicability at various GFR levels. At present, the CKD-EPI, MacIsaac and CG equations may be applied to evaluate GFR in normal, mild to moderate and severe kidney function, respectively.

Clinical observation on treatment of hyperplasia of mammary gland by Lirukang Granule.

OBJECTIVE: To explore the efficacy and mechanism of Lirukang Granule 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 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 (E(2)), 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.

[Challenges and opportunities for the development of Chinese traditional surgery].

Chinese traditional surgery, an important branch of traditional Chinese medicine, has contributed greatly to the people's health in the history. With the fast development of modern medicine, Chinese traditional surgery is faced with serious challenges and its shortcomings have appeared more and more evident. In this article, the authors analyzed some problems in the development of Chinese traditional surgery and the opportunities for its further development, and suggested that the superiorities of Chinese traditional surgery should be enhanced in its future development.