Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients.

Depression and anxiety are common comorbidities in breast cancer patients. Whether depression and anxiety are associated with breast cancer progression or mortality is unclear. Herein, based on a systematic literature search, 17 eligible studies involving 282,203 breast cancer patients were included. The results showed that depression was associated with cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)]. However, anxiety was associated with recurrence [1.17 (1.02, 1.34)] and all-cause mortality [1.13 (1.07, 1.19)] but not with cancer-specific mortality [1.05 (0.82, 1.35)]. Comorbidity of depression and anxiety is associated with all-cause mortality [1.34 (1.24, 1.45)] and cancer-specific mortality [1.45 (1.11, 1.90)]. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety, being female and of younger age (<60 years), and shorter follow-up duration (≤5 years) were related to a poorer prognosis. Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival. Further research should focus on a favorable strategy that works best to improve outcomes among breast cancer patients with mental disorders.

XIAOPI formula inhibits the pre-metastatic niche formation in breast cancer via suppressing TAMs/CXCL1 signaling.

BACKGROUND: Recent findings suggested that premetastatic niche (PMN) is a prerequisite in mediating cancer metastasis. Previously we demonstrated that XIAOPI formula could inhibit breast cancer lung metastasis via inhibiting tumor associated macrophages (TAMs)-secreted CXCL1. Herein, we aimed to explore the effects of XIAOPI formula on preventing breast cancer PMN formation and its underlying molecular mechanisms. METHODS: CXCL1 expression of TAMs was detected by qPCR and Western blotting assay. The influences of XIAOPI formula on the proliferation of TAMs and 4 T1 in the co-culture system were tested by CCK8 or EdU staining. Transwell experiment was applied to determine the effects of XIAOPI formula on the invasion ability of HSPCs and 4 T1. Breast cancer xenografts were built by inoculating 4 T1 cells into the mammary pads of Balb/c mice and lung metastasis was monitored by luciferase imaging. Immune fluorescence assay was used to test the epithelial-mesenchymal transition process and PMN formation in the lung tissues. The effects of XIAOPI formula on TAMs phenotype, hematopoietic stem/progenitor cells (HSPCs) and myeloid-derived suppressor cells (MDSCs) were determined by flow cytometry. RESULTS: It was found that XIAOPI formula could inhibit the proliferation and polarization of M2 phenotype macrophages, and reduce CXCL1 expression in a dose-dependent manner. However, M1 phenotype macrophages were not significantly affected by XIAOPI formula. TAMs/CXCL1 signaling was subsequently found to stimulate the recruitment of c-Kit+/Sca-1+ HSPCs and their differentiation into CD11b+/Gr-1+ MDSCs, which were symbolic events accounting for PMN formation. Moreover, XIAOPI formula was effective in inhibiting HSPCs activation and suppressing the proliferation and metastasis of breast cancer cells 4 T1 induced by HSPCs and TAMs co-culture system, implying that XIAOPI was effective in preventing PMN formation in vitro. Breast cancer xenograft experiments further demonstrated that XIAOPI formula could inhibit breast cancer PMN formation and subsequent lung metastasis in vivo. The populations of HSPCs in the bone marrow and MDSCs in the lung tissues were all remarkably declined by XIAOPI formula treatment. However, the inhibitory effects of XIAOPI formula could be relieved by CXCL1 overexpression in the TAMs. CONCLUSIONS: Taken together, our study provided preclinical evidence supporting the application of XIAOPI formula in preventing breast cancer PMN formation, and highlighted TAMs/CXCL1 as a potential therapeutic strategy for PMN targeting therapy. Video Abstract.

Bushen Yijing Fang Reduces Fall Risk in Late Postmenopausal Women with Osteopenia: A Randomized Double-blind and Placebo-controlled Trial.

Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, -2.5~-2 SD) were recruited and randomized to orally receive calcium carbonate 300 mg daily with either BSYJF or placebo for 36 months. The effect was further investigated for another 10-year follow-up. During the 36-month administration, there were 12 falls in BSYJF group and 28 falls in placebo group, respectively, indicating 64% lower risk of falls (RR 0.36 [95% CI, 0.18 to 0.71]; P = 0.004) in BSYJF group. During the 10-year follow-up, 36% lower fall risk (RR 0.64 [95% CI, 0.46 to 0.89]; P = 0.009) was observed in BSYJF group. No significant difference was found in safety profile between two groups. Thirty-six-month administration of BSYJF reduced fall risk with an increase in bone mass, and its latent effect on fall risk was continually observed in the 10-year follow-up in late postmenopausal women with osteopenia. This clinical trial was registered at Chinese clinical trial registry (ChiCTR-IOR-16008942).

Appraisal of clinical practice guidelines for ischemic stroke management in Chinese medicine with appraisal of guidelines for research and evaluation instrument: A systematic review.

OBJECTIVE: To systematically review the clinical practice guidelines (CPGs) for ischemic stroke in Chinese medicine (CM) with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. METHODS: CM CPGs for ischemic stroke were searched in 5 online databases and hand-searches in CPGrelated handbooks published from January 1990 to December 2012. The CPGs were categorized into evidence based (EB) guideline, consensus based with no explicit consideration of evidence based (CB-EB) guideline and consensus based (CB) guideline according to the development method. Three reviewers independently appraised the CPGs based on AGREE II instrument, and compared the CPGs' recommendations on CM pattern classification and treatment. RESULTS: Five CM CPGs for ischemic stroke were identified and included. Among them, one CPG was EB guideline, two were CB guidelines and two were CB-EB guidelines. The quality score of the EB guideline was higher than those of the CB-EB and CB guidelines. Five CM patterns in the CPGs were recommended in the EB CPG. The comprehensive protocol of integrative Chinese and Western medicine recommended in the EB CPG was mostly recommended for ischemic stroke in the CPGs. The recommendations varied based on the CM patterns. CONCLUSION: The quality of EB CPG was higher than those of CB and CB-EB CPGs in CM for ischemic stroke and integrative approaches were included in CPGs as major interventions.

Anti-angiogenic activity of Erxian Decoction, a traditional Chinese herbal formula, in zebrafish.

Erxian Decoction (EXD), a traditional Chinese herbal formula, has been used to treat menopausal symptoms and other aging diseases for several decades. Recently, our laboratory found that EXD could inhibit the proliferation of breast cancer cells. This activity may be mediated by anti-angiogenic action. To investigate the anti-angiogenic activity of EXD, its inhibitory effect on blood vessel formation was evaluated using both wild type and transgenic zebrafish embryos with fluorescent vasculature in vivo. Both semi-quantitative and real-time quantitative polymerase chain reaction (qPCR) were carried out to evaluate the effect of EXD on the expression of several genes closely associated with angiogenesis in zebrafish. EXD was found to inhibit vessel formation in zebrafish embryos in a dose- and time-dependent manner. Furthermore, it reduced the mRNA expression of vascular endothelial growth factor A (VEGF-A) and the protein level of hypoxia inducible factor 1α (HIF-1α) in the embryos, suggesting the involvement of HIF-1 mediated VEGF-A signaling pathway in the anti-angiogenic action of EXD. The anti-angiogenic activity of EXD provides new insights to its clinical application and may in the future lead to the development of potential drugs for treating various cancers, especially in menopausal period.