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Introduction Chinese medicine injections (CMIs) are widely applied to the treatment of acute cerebral infarction (ACI) in China. However, there are very few head-to-head comparative trials to determine the relative efficacy between different CMIs. It is reported that 20 kinds of CMIs are often used for treating cerebral infarction. Due to the fact that various CMIs are used in clinic, it’s difficult for clinicians to choose the optimal CMIs for patients with ACI. We plan to conduct a network meta-analysis (NMA) to compare the efficacy of 12 kinds of different CMIs, including direct and indirect comparisons between CMIs, aiming to provide the best currently available evidence base to guide the choice about CMIs treatment for patients with ACI. Methods A systematic and comprehensive search will be performed from inception to August 2018 in both English and Chinese databases, involving PubMed ,Cochrane Library, Embase, China National Knowledge Infrastructure Database (CNKI), Wanfang Database, Chongqing VIP information (CQVIP), and SinoMed. Randomized controlled trial (RCT) related to CMIs in the treatment of ACI will be included. Quality of included literature will be assessed according to the risk of bias tool of Cochrane Handbook 5.1.0. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA. Data analysis will be conducted by using STATA 13.1. Results This systematic review and NMA is to summarise the direct and indirect evidence for 12 kinds of different CMIs to manage ACI, and to rank these CMIs for CMIs treatment of patients with ACI. The findings of this NMA will be reported according to PRISMA-NMA statement. Conclusion This study will offer helpful and informative evaluations of current CMIs for ACI. The results will inform clinicians, provide optimal CMI, establish evidence gaps, and identify promising CMIs for evaluation in future trials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

Previous studies concerning the association between aspirin use and breast cancer risk yielded inconsistent results. We aimed to investigate the association by meta-analysis. PubMed and EMBASE were searched for relevant studies. We calculated the summary relative risks (RR) and 95% confidence intervals (CI) using random-effects models. Seventeen cohort studies and 15 case–control studies were included. The overall result showed that aspirin use decreased risk of breast cancer (RR, 0.90; 95% CI, 0.85–0.95). However, there was evidence of publication bias and heterogeneity and the association disappeared after correction using the trim-and-fill method. When stratified by study design, a significant benefit for aspirin users was only found in population-based and hospital-based case–control studies but not in cohort or nest case–control studies. Further subgroup analyses showed that aspirin use could decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Aspirin use may not affect overall risk of breast cancer, but decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Considering between-study significant heterogeneity and publication bias, confirmation in future studies is also essential. Cancer Epidemiol Biomarkers Prev; 24(11); 1645–55. ©2015 AACR.

Hesperidin (HDN), a flavanone glycoside, possesses anti-inflammatory properties and has been suggested to be able to modulate the lipopolysaccharide (LPS)-induced acute lung injury (ALI). High-mobility group box 1 (HMGB1) serves as an inflammatory cytokine when released extracellularly and is involved in the pathogenesis of diverse inflammatory disorders. The current study aimed to investigate the involvement of HMGB1 in HDN-induced immunoregulation of ALI. ALI in male BALB/c mice was induced by intranasal administration of LPS (0.5 mg/kg). HDN (500 mg/kg) was administered intragastrically 10 days prior to LPS exposure. HDN significantly protected animals from LPS-induced ALI as evidenced by decreased elevation of the lung wet to dry weight ratio, total cells, neutrophils, macrophages, and myeloperoxidase (MPO) activity, associated with reduced lung histological damage. In the meantime, HDN pretreatment markedly inhibited the production of pro-inflammatory cytokines and chemokine, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). Furthermore, HDN pretreatment dramatically inhibited the infiltration of macrophages and suppressed the expression and release of HMGB1 in vivo and in vitro. In addition, intranasal application of exogenous HMGB1 could result in lung injury which was also alleviated by HDN administration. These results suggest that HDN pretreatment protects mice from LPS-induced ALI via inhibiting the production of TNF-α and IL-6. Moreover, we found that HDN could inhibit the expression and release of HMGB1 via suppressing the infiltration of macrophages and production of MCP-1.

Introduction Traditional Chinese patent medicines (TCPMs) are widely used in the treatment of acute cerebral infarction (ACI) in China. Many oral traditional Chinese patent medicines have been reported to be effective for ACI. However, a comparison of randomized controlled trials (RCTs) to directly compare the efficacy of the different oral TCPMs has not been performed. There is no evidence to demonstrate which of oral TCPMs are more effective for clinicians. Therefore, we plan to conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of 10 kinds of oral TCPMs for ACI. The aim is to provide the best currently available evidence base to guide the selection of oral TCPMs. Methods A systematic and comprehensive search will be performed from inception to July 2019 in both English and Chinese databases, involving Medline, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, Chongqing VIP information, and SinoMed. All RCTs related to TCPMs in the treatment of ACI will be included. The primary outcomes are mortality, as well as the the rate of cerebrovascular event including a recurrence event. The secondary outcomes include National Institutes of Health Stroke Scale and adverse drug reactions/adverse drug events. Two reviewers will independently screen the literature by using pre-specified eligibility criteria, and assess the quality of included studies according to the risk of bias tool of Cochrane Handbook 5.1.0. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA. Data analysis will be conducted by using STATA13.0 and WinBUGS1.4.3. Results This systematic review and NMA aims to summarize the direct and indirect evidence for 10 kinds of oral TCPMs and to rank these TCPMs. The findings of this NMA will be reported according to PRISMA-NMA statement. The results of the NMA will be submitted to a peer-reviewed journal once completed. Conclusion Using NMA, this study will offer new and informative evaluations of current TCPMs for ACI. The results will inform clinicians, provide optimal clinical treatment strategies, bridge the evidence gaps, and identify promising TCPMs for evaluation in future trials. The protocol has been registered on PROSPERO (International Prospective Register of Systematic Reviews) (CRD42018110307).

Metastasis is the most lethal attribute of human malignancy. High-level expression of survivin is involved in both carcinogenesis and angiogenesis in cancer. Previous studies indicate that a mutation of the threonine residue at position 34 (Thr34Ala) of survivin generates a dominant-negative mutant that induces apoptosis, inhibits angiogenesis, and suppresses highly metastatic breast carcinoma in mouse models. We investigated the efficacy of gene therapy with a survivin dominant-negative mutant and possible factors related to lymph node metastasis. The metastasis rate was compared between each group in order to find a survivin-targeted therapy against lymphangiogenesis in its earliest stages. We established lymph node metastasis models and treated animals with H22 tumors with Lip-mSurvivinT34A (Lip-mS), Lip-plasmid (Lip-P), or normal saline (NS). Eight days after the last dose, five randomly chosen mice from each group were sacrificed. We detected the apoptotic index, microvessel density (MVD), lymphatic microvessel density (LMVD), and the expression of VEGF-D with immunohistochemistry. After the remaining animals were sacrificed, we compared the tumor-infiltrated lymph nodes in each group. Administration of mSurvivinT34A plasmid complexed with cationic liposome (DOTAP/chol) resulted in the efficacious inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor model. These responses were associated with tumor cell apoptosis, and angiogenesis and lymphangiogenesis inhibition. Our results suggested that Lip-mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and lymphangiogenesis, thus suppressing tumor growth and lymphatic metastasis. The mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit lymphatic metastasis.

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We investigated IgA and IgG levels against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1) in serum of 223 women with breast cancer (BC) and 309 controls in Guangzhou, China. VCA IgA levels were significantly associated with an elevated risk of BC, with adjusted ORs (95%CIs) of 1.70 (1.05-2.76) (seropositivity) and 2.21 (1.11-4.40) (unit increases in OD value). This association was stronger among young, lean, and HER2+ women. The EBNA-1 IgA levels in OD value, but not seropositivity, were associated with an increased risk of BC among ER+, PR+, and HER2+ patients. None of the IgG variables was related to BC. These results suggest the EBV association with BC in an endemic area of nasopharyngeal carcinoma.

Due to the capacity limitation, congestions caused by the excessive amount of passenger flow appear in many Mass Transit Railway(MTR) hubs. Computer simulation is one of the most effective way to solve this problem. In this paper, an identification and elimination of capacity bottlenecks method was proposed based on dynamic movement of passengers simulation. Possible optimized solution was investigated through a case study in XiErqi Station, which is the transfer hub of Line13 and Changping Line in Beijing MTR. The proposed model was validated both statically and experimentally. Two optimization measures were dicussed after digging out the passenger feature and the essence of the congestions. One is improving passenger flow organization, the other is reforming operation organization. Then the simulate experiments were done through a proprietary software developed by Beijing Jiaotong University----SRail System. The simulation result shows congestion was alleviated effectively. It is proved that the method is feasible and effective.

Family history of nasopharyngeal carcinoma (NPC) is an established risk factor for this cancer, but the contributions of family history of other types of cancer and its interaction with environmental factors have not been well characterized.A total of 1845 incident cases of NPC and 2275 matched controls from Guangdong, China were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models adjusted for smoking, consumption of alcohol, salted fish consumption, and demographic factors.A significant association between the risk of NPC and family history of any cancers in first degree relatives was observed, and higher number of affected family member was related to a higher risk (P(trend)0.01). Family history of NPC was the strongest predictor for NPC (OR: 3.35, 95% CI: 2.46-4.55 for all first degree relatives). The risk of NPC was also positively associated with history of head and neck cancer among parents and lung and breast cancers among siblings. The combination of family history of cancer, especially NPC, and the consumption of salt-preserved fish significantly increased the risk for NPC.These results confirm that the risk for NPC increases with family history of NPC and suggest that lung and breast cancer contribute to risk for NPC. A possible interaction between family history of cancer, especially NPC, and consumption of salt-preserved fish in the development of NPC was also identified.

Patients with localized prostate cancer can usually achieve initial response to conventional treatment. However, most of them will inevitably progress to advanced disease stage. There is a clear need to develop innovative and effective therapeutics for prostate cancer. Mouse survivin T34A (mS-T34A) is a phosphorylation-defective Thr34 → Ala dominant negative mutant, which represents a potential promising target for cancer gene therapy. This study was designed to determine whether mS-T34A plasmid encapsuled by DOTAP-chol liposome (Lip-mS) has the anti-tumor activity against prostate cancer, if so, to further investigate the possible mechanisms. In vitro, TRAMP-C1 cells were transfected with Lip-mS and examined for apoptosis by PI staining and flow cytometric analysis. In vivo, subcutaneous prostate cancer models were established in C57BL/6 mice, which were randomly assigned into three groups to receive i.v. administrations of Lip-mS, pVITRO2-null plasmid complexed with DOTAP-chol liposome (Lip-null) or normal saline every 2 days for eight doses. Tumor volume was measured. Tumor tissues were inspected for apoptosis by TUNEL assay. Microvessel density (MVD) was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cell test was conducted to evaluate the treatment effect on angiogenesis. Administration of Lip-mS resulted in significant inhibition in the growth of mouse TRAMP-C1 tumors. The anti-tumor response was associated with increased tumor cell apoptosis and decreased microvessel density. The present study may be of importance in the exploration of the potential application of Lip-mS in the treatment of a broad spectrum of tumors.

Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. Here we investigate the effects of two novel liver x receptor (LXR) ligands (T0901317 or GW3965) on the development of acquired resistance to an EGFR TKI gefitinib. We observed known mechanisms of acquired resistance to EGFR TKI, including the EGFR T790M mutation, MET gene amplification and loss of PTEN in the gefitinib-resistant HCC827-8-1 cells. However, we found expression of MET was lower in HCC827-8-1 cells than in HCC827 cells. T0901317 or GW3965 inhibited Akt activation and sensitized HCC827-8-1 cells to gefitinib-induced cytotoxicity. In contrast, LXR ligands alone had no significant effect on HCC827-8-1 cells. In conclusion, this combined treatment may be of interest for treatment of lung adenocarcinomas harboring EGFR mutations and acquired resistance to gefitinib.

While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr-resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co-culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes.

Background Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-α (TNF-α), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-α on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-α on acute liver injury induced by carbon tetrachloride (CCl4). Methods SD male rats were equally divided into nine groups. CCl4 (1 ml/kg) was subcutaneously injected into the rats. Enbrel, a TNF-α inhibitor, were intraperitoneally injected at dose of 0, 0.25, 0.5, 1, 2, 4 or 8 mg/kg 15 min before the CCl4 injection. 24 h later, rats were sacrificed. Serum ALT and AST were measured with an autoanalyzer. Serum TNF-α were measured by ELISA. HE staining was used to observe the liver tissue morphology. Hepatocellular apoptosis were tested by immunochemistry and Tunnel kit. Inflammatory factors, involve IL-4, IL-6, IL-8, IL-β and IFN-γ were detected by RT-PCR. The NF-κB signal pathway and anti-apoptotic genes include Bcl-XL, FHC, XIAP and Bcl-2 were measured by western-blotting and RT-PCR. Results The change of liver function presented an obvious “V” shape in the whole process of persistently increased Enbrel. As Enbrel was increased gradually from 0 to 1 mg/kg, serum TNF-α were blocked, ALT and AST were gradually decreased as TNF-α as well as the numbers of hepatocellular apoptosis, and were declined to the minimum at 1 mg/kg Enbrel. As Enbrel was increased gradually from 1 to 8 mg/kg, ALT, AST and hepatocellular apoptosis were increased instead, and reached to the maximum at 8 mg/kg Enbrel. HE showed that the seriousness of hepatocellular steatosis was the most at 8 mg/kg Enbrel, and second at 0 mg/kg, the weakest at 1 mg/kg in the acute liver injury. Western-blotting and RT-PCR showed NF-κB, p-IκBα and antiapoptotic genes include Bcl-XL, FHC, XIAP, Bcl-2 were decreased as TNF-α was blocked by increased Enbrel. Conclusion Our results suggested that TNF-α had a dual role in acute liver injury. It was regulated might via the corporate effect of NF-κB signal pawahway and anti-apoptosis. Meanwhile, our findings provide a reference for clinical treatment of acute liver injury. Electronic supplementary material The online version of this article (doi:10.1186/s13578-016-0074-x) contains supplementary material, which is available to authorized users.

The decrease of station service level of urban rail transit (URT) is caused by passenger flow congestion, especially in peak hours. It seriously influences the safety of URT daily operation. The existing evaluation methods mainly depend on pedestrian flow indexes. In this paper, a new evaluation method based on travel time delay using the mining technology of automatic fare collection (AFC) data is proposed to provide passenger-oriented service information by synthetic indexes: congestion delay, generalized stranded times, and the number of stranded passengers. To avoid the transfer influence, the authors selected the specific data, whose origin station and destination station are in the same line. Finally, Beijing Subway is used as a case study to verify this method. Results suggest that the proposed method can effectively assess the station service level.

Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor, which is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. Dermatological reactions are the most common adverse events associated with gefitinib treatment; other adverse effects, including diarrhea, nausea, stomatitis and an asymptomatic elevation of liver enzymes have also been reported. The present study describes a patient with intestinal obstruction who was successfully undergoing treatment with gefitinib for primary and metastatic neoplasms. Gefitinib-induced intestinal obstruction has not been previously reported; therefore, careful monitoring of gastrointestinal symptoms should be conducted throughout the course of gefitinib-treated malignancies.

Propofol-paravertebral anesthesia (PPA) is a unique combination of paravertebral nerve blocks (PVBs) and propofol that regulates the cellular microenvironment during surgical period. Growing evidence points to its ability to attenuate perioperative immunosuppression of cancers. Abundant studies show that cancer patients who undergo perioperative PPA exhibit less recurrence as well as metastasis. Breast cancer remains a leading cause of cancer-induced death in women. Over the last decades, increasing concerns have been put on the promotional role of PPA in the prognosis of breast cancer patients. Among them, PPA participates in several bioprocesses in the development of breast cancer, including inhibiting hypoxia-inducible factor (HIF) activity, elevating serum concentration of nitric oxide index (NOx), depression of the neuroepithelial cell transforming gene 1 (NET1) signal pathway, blocking the nuclear factor kappa B (NF-κB) pathway following an decreased expression of matrix metalloproteinase (MMP), increasing NK cytotoxicity, and affecting transforming growth factor (TGF)-β-targeted ras and HER2/neu gene pathways. In this review, we discuss the effect of PPA on breast cancer metastasis and progression. This will provide an alteration pattern of surgical anesthesia technique in breast cancer patients with poor prognosis.

Breast cancer (BCa) is one of the major deadly cancers in women. However, treatment of BCa is still hindered by the acquired-drug resistance. It is increasingly reported that exosomes take part in the development, metastasis, and drug resistance of BCa. However, the specific role of exosomes in drug resistance of BCa is poorly understood. In this study, we investigate whether exosomes transmit drug resistance through delivering miR-222. We established an adriamycin-resistant variant of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line (MCF-7/Adr) from a drug-sensitive variant (MCF-7/S). Exosomes were isolated from cell supernatant by ultracentrifugation. Cell viability was assessed by MTT assay and apoptosis assay. Individual miR-222 molecules in BCa cells were detected by fluorescence in situ hybridization (FISH). Then, FISH was combined with locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH). Individual miR-222 could be detected as bright photostable fluorescent spots and then the quantity of miR-222 per cell could be counted. Stained exosomes were taken in by the receipt cells. MCF-7/S acquired drug resistance after co-culture with exosomes from MCF-7/Adr (A/exo) but did not after co-culture with exosomes from MCF-7/S (S/exo). The quantity of miR-222 in A/exo-treated MCF-7/S was significantly greater than in S/exo-treated MCF-7/S. MCF-7/S transfected with miR-222 mimics acquired adriamycin resistance while MCF-7/S transfected with miR-222 inhibitors lost resistance. In conclusion, exosomes are effective in transmitting drug resistance and the delivery of miR-222 via exosomes may be a mechanism.

Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients.

Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.

The guiding problem in railway stations is evident, for that its designing lacks an evaluation standard and basis. This article analyzes the interactive features between passenger way-finding behaviors and guiding sign based on man-environment theory, introduces dynamic evaluation notion and proposes the principle of input, output, and modeling of guiding sign assessment simulation in the whole process. Finally, a case study of Beijing south station has been made, using the “G-Sign” system developed autonomously. Also the research proposes some qualitative and quantitative basics for guiding signs design, which could provide references for making guiding sign design standard.

Strontium has been widely used in industries like electronic and pharmacy. It has a carcinogenic potential, however, and no study has been conducted to evaluate its effects on cancer risk. The aim of this study was to explore the possible association between strontium and breast cancer risk in a case-control study including 240 incident invasive breast cancer patients and 246 age-matched controls. We measured the urinary concentrations of strontium by inductively coupled plasma mass spectrometry, and conducted face-to-face interviews to obtain information on potential breast cancer risk factors. Multivariable analysis was used to estimate the association. Creatinine-adjusted levels [median (25th, 75th) μg/g] of strontium were 155.59 (99.05, 230.70) in the breast cancer patients and 119.62 (81.97, 163.76) in the controls. Women in the highest tertile of strontium showed 124% increased risk of breast cancer, when compared with those in the lowest tertile after adjustment for the potential risk factors [OR (95% CI): 2.24 (1.42-3.81)]. This association was particularly strong for HER2 positive breast cancer [OR (95% CI): 10.92 (3.53-33.77)], and only occurred among premenopausal women. These results suggest a potential role of strontium in the development of breast cancer and urge further studies on the environmental contamination and the physiological and pathological mechanisms of strontium.