Vascular maturity and functionality are closely associated with tumor progression and chemosensitivity. The antidiabetic agent metformin has shown its ability to inhibit tumor angiogenesis in metastatic breast cancer models. However, it remains unclear if or how metformin remodels the abnormal vasculature of metastatic breast cancer, while inhibiting angiogenesis. Metastatic breast cancer models were constructed to compare microvessel density (MVD), vascular maturity and function, lung metastasis and chemosensitivity in metformin-treated or untreated mice. Protein array assay and transcriptome sequencing were performed for genetic screening. Lentiviral shRNA-PDGF-B transfection was used for observing the contribution of PDGF-B knockdown to metformin’s vascular effects. Metastatic breast cancers were characterized by an excessively angiogenic, immature and morphologically abnormal vasculature. Compared to control, metformin significantly reduced MVD, leakage and hypoxia, and increased vascular mural cells coverage and perfusion, namely, “vessel normalization”. Metformin at human blood concentrations had no direct effect on the migration and proliferation of cancer cells. Based on that, reduced lung metastasis of the primary tumor and improved chemosensitization by metformin were assumed to be mediated via metformin’s vascular effects. Further results of genetic screening and in vivo experiments showed that the downregulation of platelet-derived growth factor B (PDGF-B) greatly contributed to the metformin-induced vessel normalization. These findings provide pre-clinical evidences for the vascular mechanism of metformin-induced metastasis inhibition and the chemosensitization of metastatic breast cancers.

Triple Negative Breast cancer (TNBC) is incurable cancer with higher rates of relapse and shorter overall survival compared with other subtypes of breast cancer. Cellular retinoic acid binding protein 2 (CRABP2) belongs to fatty acid binding protein (FABP) family which binds with all-trans retinoic acid (RA). Previous studies from the database have reported the patients with high expression of CRABP2 showed different prognosis in ER+ and ER− breast cancer. However, its biological role and exact mechanism in breast cancer remain unknown. This aim of this study was to explore how CRABP2 regulated invasion and metastasis based on the estrogen receptor-α (herein called ER) status in breast cancer. Immunohistochemical staining method was used to analyze the expression of CRABP2 in human breast cancer tissues. Lentivirus vector-based shRNA technique was used to test the functional relevance of CRABP2 knockdown in breast tumors. Tail vein injection model was used to examine the lung metastasis. Co-immunoprecipitation, Western blotting, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to investigate the underlying mechanism that influenced the ER to the regulation of CRABP2 to Lats1. We observed that knockdown of CRABP2 promotes EMT, invasion and metastasis of ER+ breast cancer cells in vitro and in vivo, whereas overexpression of CRABP2 yields the reverse results. In ER+ mammary cancer cells, the interaction of CRABP2 and Lats1 suppress the ubiquitination of Lats1 to activate Hippo pathway to inhibit the invasion and metastasis of ER+ mammary cancer. However, in ER− mammary cancer cells, the interaction of CRABP2 and Lats1 promote the ubiquitination of Lats1 to inactivate Hippo pathway to promote the invasion and metastasis of ER− mammary cancer. Our findings indicate that CRABP2 can suppress invasion and metastasis of ER+ breast cancer and promote invasion and metastasis of ER− breast cancer by regulating the stability of Lats1 in vitro and in vivo, and it provides new ideas for breast cancer therapy.

Compared with open esophagectomy (OE), minimally invasive esophagectomy (MIE) proves to have clear benefits in reducing the risk of pulmonary complications for patients with resectable esophageal cancer. The objectives of our study were to explore the superiority of MIE in reducing the occurrence of anastomotic leakages (ALs) when compared to OE. A systematic review and meta-analysis was performed to assess the superiority of MIE on the occurrence of ALs over OE, by searching many sources (through December, 2014) such as Medline, Embase, Wiley Online Library, and Cochrane Library. Fixed-effects model was used to calculate summary odds ratios (ORs) to quantify associations between OE and MIE groups. Cochran’s Q and I 2 statistics were used to evaluate heterogeneity among studies. Among a total of 43 studies involving 5537 patients included in the meta-analysis, 2527 (45.6 %) cases underwent MIE and 3010 (54.4 %) cases underwent OE. Compared to patients undergoing OE, patients undergoing MIE did not have statistical significance in reduced occurrence of ALs (OR = 0.97, 95 % CI = 0.80–1.17). Insignificant reduced occurrence of ALs was not associated with anastomotic location (OR = 0.90, 95 % CI = 0.71–1.13) or anastomotic procedure (OR = 1.02, 95 % CI = 0.79–1.30). More proofs are needed to clarify the strengths or weaknesses of MIE in preventing anastomotic leakages after esophagectomy for cancer. A largely randomized, controlled trial should be undertaken to resolve this contentious issue urgently.

Background: Research on the incidence, mortality, and disability-adjusted life years (DALYs) of female breast and gynecologic cancers (FeBGCs) and the relevant risk factors for adolescents and young adults (AYAs) are valuable for policy-making in China. We aimed to estimate the incidence, deaths, and DALYs and predict epidemiological trends of FeBGCs among AYAs in China between 1990 and 2019.Methods: Data from the 2019 Global Burden of Disease (GBD) study between 1990 and 2019 in 195 countries and territories were retrieved. Data about the number of FeBGC incident cases, deaths, DALYs, age-standardized rates (ASRs), and estimated annual percentage changes (EAPCs) were extracted. A comparative risk assessment framework was performed to estimate the risk factors attributable to breast cancer deaths and DALYs, and autoregressive integrated moving average (ARIMA) models were fitted for time-series analysis to predict female cancer morbidity and mortality among Chinese AYAs until 2030.Results: In 2019, there are 61,038 incidence cases, 8,944 deaths, and 529,380 DALYs of FeBGCs among the AYAs in China, respectively. The estimated annual percentage change (EAPC) values were positive scores (>0) in ASIRs and negative scores (<0) in ASMR and ASDR. Furthermore, in 2030, the incidence rate of FeBGCs would grow to 30.49 per 100,000 in China, while the mortality rate would maintain a steady state. Of the deaths and DALYs, diet high in red meat was the greatest contributor to breast cancer, while a high body mass index (BMI) was the greatest contributor to cervical, ovarian, and uterine cancers.Conclusion: The increasing Chinese FeBGC burden is mainly observed in AYAs and non-red meat diet, and the control of body weight could reduce FeBGC burden in China.

Unsafe sex has become a public safety problem that endangers society, and research on deaths and disability-adjusted life years (DALYs) related to unsafe sex is valuable for global policy-making. We aimed to estimate the deaths and DALYs attributable to unsafe sex by country, gender, age group, and sociodemographic status from 1990 to 2019. We extracted data on disease burden from the Global Disease Burden 2019 (GBD 2019) database for unsafe sex, including deaths, DALYs and age-standardized rates (ASRs). Comparative analyses were performed on data about deaths, DALYs and the responding ASRs attributable to unsafe sex in different countries and regions using the Social Demographic Index (SDI). The global age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) attributable to unsafe sex were 11.98 (95% uncertainty intervals (UI): 10.97–13.52) per 100,000 people and 570.78 (95% UI: 510.24–658.10) per 100,000 people, respectively. Both the ASMRs and ASDRs were the highest in southern sub-Saharan Africa and lowest in Australasia and decreased with increasing SDI levels. About unsafe-sex-related disease, HIV/AIDS has the highest ASMR [8.48 (95% UI: 7.62–9.95)/100,000 people] and ASDR [447.44 (95% UI: 394.82–533.10)/100,000 people], followed by Cervical cancer [ASMR: 3.40 (95% UI: 2.90–3.81)/100,000 people and ASDR: 107.2 (95% UI: 90.52–119.43)/100,000 people] and sexually transmitted infections excluding HIV [ASMR: 0.10 (95% UI: 0.08–0.11)/100,000 people and ASDR: 16.14 (95% UI: 10.51–25.83)/100,000 people]. The death and DALY burden caused by these three diseases were more serious in the over 75 years old age group. The 40–44 age group for men and the 35–39 age group for women had the highest population of unsafe sex-related deaths and DALYs, respectively. In addition, the burden of unsafe sex in women was more serious than those in men. Unsafe sex is an important risk factor for global disease burden and a leading cause of substantial health loss. We found that the risk of ASMRs and ASDRs attributable to unsafe sex had negative correlation with SDI levels. These results demonstrate that the need for revised policies that focus on efforts to reduce overall unsafe sex worldwide.

Background: Breast cancer‐related lymphedema (BCRL) is one of the common postoperative complications that severely affects the functions of the arm and quality of life. Since lymphedema is difficult to treat and prone to recurrence, early prevention of lymphedema is crucial.Methods: Patient diagnosed with breast cancer (N = 108) were randomized to the intervention (n = 52) or control group (n = 56). In the intervention group, patients were provided the lymphedema prevention program based on the theory of knowledge–attitude–practice during the perioperative period and the first three chemotherapy sessions (mainly includes health education, seminars, knowledge manuals, sports guidance, peer education, and WeChat group).The limb volume, handgrip strength, arm function, and quality of life were measured in all patients at the baseline, 9 weeks (T1), and 18 weeks (T2) after surgery.Results: The incidence of lymphedema in the Intervention group was numerically lower than in the control group after implementing the lymphedema prevention program, but the difference was not statistically significant (T1: 1.9% vs. 3.8%, p = 1.000; T2: 3.6% vs. 7.1%, p = 0.744). However, compared with the control group, the intervention group showed there was less deterioration in handgrip strength (T1 [t = −2.512, p < 0.05] and T2 [t = −2.538, p < 0.05]), improved postoperative upper limb dysfunction (T1 [t = 3.087, p < 0.05] and T2 [t = 5.399, p < 0.05]) and less deterioration in quality of life (T1 [p < 0.05] and T2 [p < 0.05]).Conclusion: Although the investigated lymphedema prevention program improved arm function and quality of life, it did not reduce the incidence of lymphedema in postoperative breast cancer patients.