Lonp1 and Sig-1R contribute to the counteraction of ursolic acid against ochratoxin A-induced mitochondrial apoptosis.

Ochratoxin A (OTA), a secondary fungal metabolite with nephrotoxicity, is widespread in numerous kinds of feeds and foodstuffs. Ursolic acid (UA), a water-insoluble pentacyclic triterpene acid, exists in a wide range of food materials and medicinal plants. Our earlier researches provided preliminary evidence that mitochondria- and mitochondria-associated endoplasmic reticulum membranes (MAMs)-located stress-responsive Lon protease 1 (Lonp1) had a protective function in OTA-induced nephrotoxicity, and the renoprotective function of UA against OTA partially due to Lonp1. However, whether other MAMs-located protiens, such as endoplasmic reticulum stress (ERS)-responsive Sigma 1-type opioid receptor (Sig-1R), contribute to the protection of UA against OTA-induced nephrotoxicity together with Lonp1 needs further investigation. In this study, the cell viability, reactive oxygen species, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells varied with OTA and/or UA/CDDO-me/AVex-73/Sig-1R siRNA treatments were determined. Results indicated that a 24 h-treatment of 5 µM OTA could significantly induce mitochondrial-mediated apoptosis via repressing Lonp1 and Sig-1R, thereby enhancing the protein expressions of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α, and Bax, and inhibiting the protein expression of Bcl-2 in HK-2 cells, which could be remarkably relieved by a 2 h-pre-treatment of 4 µM UA (P < 0.05). In conclusion, through mutual promotion between Lonp1 and Sig-1R, UA could effectively relieve OTA-induced apoptosis in vitro and break the vicious cycle between oxidative stress and ERS, which activated the mitochondrial apoptosis pathway.

A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting.

PURPOSE: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. METHODS: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. RESULTS: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37). CONCLUSIONS: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy. IMPLICATIONS FOR CANCER SURVIVORS: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.

Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study.

BACKGROUND: Recent evidence suggests that vitamin D might lower breast cancer mortality. There is also growing interest in vitamin D's potential association with health-related quality-of-life (HRQoL). Associations between circulating 25-hydroxyvitamin D (25OHD) concentrations and HRQoL were examined prospectively among breast cancer survivors at the time of diagnosis and 1 year later. METHODS: 504 women with incident early-stage breast cancer at Roswell Park Comprehensive Cancer Center were included, and 372 patients provided assessments 1 year later. At each timepoint, participants provided blood samples and completed the SF-36 Health Survey, and surveys on perceived stress, depression, and fatigue. Season-adjusted serum 25OHD concentrations were analyzed in relation to HRQoL measures using multivariable logistic regression models. RESULTS: Approximately 32% of participants had deficient vitamin D levels at diagnosis, which decreased to 25% at 1 year. Concurrently, although SF-36 physical health summary scores were lower at 1 year, mental health summary scores improved, and levels of depression and perceived stress were lower. In comparison with women with sufficient 25OHD levels (>30 ng/mL) at diagnosis, those who were deficient (<20 ng/mL) had significantly worse HRQoL at diagnosis and 1 year later. Vitamin D deficiency 1 year post-diagnosis was also associated with worse HRQoL, particularly among breast cancer survivors who took vitamin D supplements. CONCLUSIONS: Breast cancer survivors with vitamin D deficiency were more likely to report lower HRQoL than those with sufficient levels at the time of diagnosis and 1 year post-diagnosis. IMPACT: Our results indicate a potential benefit of vitamin D supplementation for improving breast cancer survivorship.

Lack of racial differences in clinical outcomes of breast cancer patients receiving neoadjuvant chemotherapy: a single academic center study.

PURPOSE: To examine the association between race and clinical outcomes (pathological complete response [pCR]; recurrence-free survival [RFS], and overall survival [OS]) in patients diagnosed with triple-negative (TNBC) or HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: Patients who self-identified as non-Hispanic white (NHW) or non-Hispanic Black (NHB) and were diagnosed with Stage I-III TNBC (n = 171 including 124 NHW and 47 NHB) and HER2-positive (n = 161 including 136 NHW and 25 NHB) breast cancer who received NAC from 2000 to 2018 at Roswell Park Comprehensive Cancer Center were included. Associations of race with pCR and survival outcomes were evaluated using logistic and Cox regression models, respectively. RESULTS: There was no statistically significant difference in pCR between NHB and NHW patients with TNBC (31.9 vs 29.8%; OR: 1.11, 95% CI 0.54-2.29) or HER2-positive breast cancer (36.0 vs 39.7%; OR: 0.87, 95% CI 0.36-3.11). After controlling for potential confounders, including age, stage, treatment regimens, insurance status, and comorbidities, no statistically significant difference in OS or RFS was observed between NHB and NHW patients within either subtype. CONCLUSION: TNBC or HER2-positive breast cancer patients treated at a single academic center in Buffalo, NY, showed similar outcomes independent of patients' race. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography, and clinical outcomes are warranted.

Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line.

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry.

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed ~10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity (p < 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., Klebsiella, Lactobacillus, Slackia, Senegalimassilia) were unique to each group. Bacteria (e.g., Fusobacteria, Pyramidobacter and Odoribacter) previously associated with colorectal cancer and cardiovascular disease, both diet-related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.

Neuronal Autophagy in Depression and Regulatory Effect of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Depression is a mental illness characterized by persistent negative feelings， which has seriously threatened people's health. In recent years， neuronal autophagy， an important stress response， has also been regarded as a hypothesis for the pathogenesis of depression. Relevant studies have shown that either insufficient or excessive autophagy triggers neuronal damage， and activated or inhibited neuronal autophagy can be observed in animal models of depression. Therefore， neuronal autophagy may be a double-edged sword involved in the pathogenesis of depression. It is believed in traditional Chinese medicine （TCM） that the occurrence of this disease is closely related to liver depression and spleen deficiency. Chinese medicine regulates the neuronal autophagy via multiple ways. The TCM monomers that regulate neuron autophagy are capable of protecting nerves or penetrating the blood-brain barrier. TCM compounds designed for soothing liver or invigorating spleen have been proved effective against this disease， demonstrating that the core pathogenesis of depression lies in liver depression and spleen deficiency. The regulatory effects of TCM on neuronal autophagy in depression models might result from its action on multiple targets， multiple pathways， and multiple systems. This paper discussed the limitations in current research based on the involvement of neuronal autophagy in depression and its treatments， in order to provide ideas for later similar research and that concerning TCM treatment of depression.

Discussion on Pathogenesis of Tumor Based on Theory of Exogenous Pathogenic Factors / 中国实验方剂学杂志

With the emerging cases of tumor is about to exceed 4 million per year in China， tumor prevention and control is also a formidable barrier hitting the world. Overall， an increasing trend of incidence and mortality of tumor in China has been observed in recent years， and the high mortality and low cure rate of tumor have seriously threaten the health of Chinese people， greatly affected the quality of life of patients， greatly reduced the living standard of patients and endangered the physical and mental health of patients. Traditional Chinese medicine（TCM） believes that the etiology of tumor is complex and pathogenesis is variable， which is the result of interaction between internal and external factors. If the treatment is carried out based on syndrome differentiation in time at the beginning when exogenous pathogens act on the human body， so as to prevent the spread of latent pathogen in human body， the occurrence and development of tumor diseases will be significantly reduced. Therefore， the theory of exogenous pathogenic factors and the pathogenesis of tumor need to be further explored. A total of 67 Chinese and English literatures were searched out with key words like external contraction， pathogenic Qi， TCM， tumor and pathogenesis in China National Knowledge Infrastructure （CNKI） and Public Medline （PubMed） databases for reference， so as to discuss the theory of exogenous pathogens and the pathogenesis of tumor comprehensively. The important role of exogenous pathogens in tumor pathogenesis and the significance of TCM in the early prevention and treatment of tumors were emphasized. Exogenous pathogenic factors such as wind， cold， dampness， fire， natural and social factors， diet and living conditions lead to the complexity of the occurrence of tumors. TCM can effectively prevent and intervene in the early stage of tumor onset， contribute to disease prevention and tumor resistance， reduce the occurrence， development and transformation of tumors， and make the clinical medication more effective， more accurate and more targeted， so as not to miss the opportunity for treating tumor， and provide a more clear guidance for clinical treatment of tumors.

Study Progress in Pathogenesis of Cancer Cachexia and Prevention and Treatment with Traditional Chinese Medicine / 中国实验方剂学杂志

Objective:The incidence rate of cancer cachexia is high in late stage of cancer， which is characterized by skeletal muscle atrophy and rapid reduction of adipose tissue and systemic inflammation. Cachexia is highly related to a variety of tumors， and causes a large proportion of cancer deaths. Cancer cachexia can lead to serious complications in patients with cancer， then， the quality of life of patients decreases， the psychological state becomes negative， and the state of illness is further worsened. At present， there is no effective intervention means to completely reverse cachexia. The combined use of multiple targets and effective components of traditional Chinese medicine（TCM）， as well as the treatment based on syndrome differentiation and the theory of TCM play an important role in the prevention and treatment of cancer cachexia. Therefore， exploring the pathogenesis of cancer cachexia and prevention and treatment with TCM is helpful for basic study and clinical application. Method:In this paper， cancer cachexia and TCM in China national knowledge infrastructure （CNKI） and Public Medline （PubMed） databases were retrieved， and 98 Chinese and English literatures were included through summarization to elaborate the pathogenesis of cancer cachexia and the prevention and treatment of TCM. Result:Emphasis was given to the important role of inflammatory reaction， skeletal muscle atrophy， energy metabolism abnormality and multiple signal joint regulation in occurrence of cancer cachexia， and the unique advantages and significant role of TCM in treatment of cancer cachexia under different treatment principles. Conclusion:Inflammatory reaction， skeletal muscle atrophy， abnormal energy metabolism make the pathogenesis of cancer cachexia complex and diverse. TCM prescriptions， Chinese herbal medicine and their effective ingredients have the natural advantages of targeting multiple pathways， controlling multiple signal pathways and inhibiting various inflammatory factors in the prevention and treatment of cancer cachexia， and are safe and effective in improving diet， prolonging the survival period of patients and keeping weight.

Intake of vitamin D and calcium, sun exposure, and risk of breast cancer subtypes among black women.

BACKGROUND: The randomized placebo-controlled Vitamin D and Omega-3 Trial suggested a possible benefit of vitamin D on cancer incidence among black individuals. However, data are limited regarding the impact of vitamin D on breast cancer subtypes among African-American/black women, who tend to develop more aggressive forms of breast cancer. OBJECTIVES: We hypothesize that more vitamin D exposure (through diet, supplements, and sunlight) and higher intake of calcium are associated with decreased risk of estrogen receptor (ER)+ and ER- breast cancer, and of triple-negative breast cancer (TNBC) among black women. METHODS: This study was conducted among 1724 black cases and 1233 controls in the Women's Circle of Health Study (WCHS) and WCHS2. Polytomous logistic regressions were used to estimate ORs and 95% CIs of ER+ and ER- breast cancer; logistic regressions were used for TNBC. The ORs from each study were pooled using an inverse-variance-weighted random-effects model. RESULTS: Dietary vitamin D and calcium intake were not associated with risk of breast cancer subtypes in the pooled analysis. For supplemental vitamin D, we observed possible inverse associations between intake of ≤800 IU/d (compared with nonuse) and risk of several subtypes, with effects that appeared strongest for TNBC (OR: 0.58; 95% CI: 0.35, 0.94); no association was found for >800 IU/d. More daylight hours spent outdoors in a year was associated with lower risk of ER+, ER-, and TNBC (e.g., highest compared with lowest quartile: TNBC OR: 0.53; 95% CI: 0.31, 0.91; P-trend = 0.02). CONCLUSIONS: Moderate supplemental vitamin D intake was associated with decreased risk of TNBC, and increased sun exposure was associated with reduced risk of ER+, ER-, and TNBC among black women.

Germline Genetic Variants in GATA3 and Breast Cancer Treatment Outcomes in SWOG S8897 Trial and the Pathways Study.

INTRODUCTION: GATA3 is a critical transcription factor in maintaining the differentiated state of luminal mammary epithelial cells. We sought to determine the prognostic and predictive roles of GATA3 genotypes for breast cancer. PATIENTS AND METHODS: Twelve single nucleotide polymorphisms (SNPs) were genotyped in 2 breast cancer cohorts, including the SWOG S8897 trial where patients were treated with adjuvant chemotherapy (CAF [cyclophosphamide, doxorubicin, 5-fluorouracil] vs. CMF [cyclophosphamide, methotrexate, 5-fluorouracil]) or untreated, and the observational Pathways Study. RESULTS: In the S8897 trial, rs3802604 and rs568727 were associated with disease-free survival and overall survival in the treated group, regardless of chemotherapy regimen. The GG genotype of rs3802604 conferred poorer overall survival (adjusted hazard ratio, 2.45; 95% confidence interval, 1.48-4.05) and disease-free survival (adjusted hazard ratio, 1.95; 95% confidence interval, 1.27-2.99) compared with the AA genotype. Similar associations were found for rs568727. In contrast, no association with either SNP was found in the untreated group. Subgroup analyses indicated that these 2 SNPs more strongly influenced outcomes in the patients who also received tamoxifen. However, the associations in the subgroup with tamoxifen treatment were not replicated in the Pathways Study, possibly owing to substantial differences between the 2 patient cohorts, such as chemotherapy regimen and length of follow-up. Results from joint analyses across these 2 cohorts were marginally significant, driven by the results in S8897. Bioinformatic analyses support potential functional disruption of the GATA3 SNPs in breast tissue. CONCLUSIONS: The present study provides some evidence for the predictive value of GATA3 genotypes for breast cancer adjuvant therapies. Future replication studies in appropriate patient populations are warranted.

Protective effects of Shenmai injection on intestinal mucosal barrier function in severely scalded rats / 中国应用生理学杂志

OBJECTIVE@#To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% 3° scald, and to provide experimental basis for the prevention and control of enterogenic infection.@*METHODS@#A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured.@*RESULTS@#Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P＜0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P＜0.05 or P＜0.01).@*CONCLUSION@#Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.

Increased cardiac sympathetic nerve activity in ovine heart failure is reduced by lesion of the area postrema, but not lamina terminalis.

Increased cardiac sympathetic nerve activity (CSNA) is a key feature of heart failure (HF) and is associated with poor outcome. There is evidence that central angiotensinergic mechanisms contribute to the increased CSNA in HF, but the central sites involved are unknown. In an ovine, rapid pacing model of HF, we investigated the contribution of the lamina terminalis and area postrema to the increased CSNA and also the responses to fourth ventricular infusion of the angiotensin type 1 receptor antagonist losartan. Ablation of the area postrema or sham lesion (n = 6/group), placement of lamina terminalis lesion electrodes (n = 5), and insertion of a cannula into the fourth ventricle (n = 6) were performed when ejection fraction was ~ 50%. When ejection fraction was < 40%, recording electrodes were implanted, and after 3 days, resting CSNA and baroreflex control of CSNA were measured before and following lesion of the lamina terminalis, in groups with lesion or sham lesion of the area postrema and before and following infusion of losartan (1.0 mg/h for 5 h) into the fourth ventricle. In conscious sheep with HF, lesion of the lamina terminalis did not significantly change CSNA (91 ± 2 vs. 86 ± 3 bursts/100 heart beats), whereas CSNA was reduced in the group with lesion of the area postrema (89 ± 3 to 45 ± 10 bursts/100 heart beats, P < 0.01) and following fourth ventricular infusion of losartan (89 ± 3 to 48 ± 8 bursts/100 heartbeats, P < 0.01). These findings indicate that the area postrema and brainstem angiotensinergic mechanisms may play an important role in determining the increased CSNA in HF.

Changes in bone mineral density in women with breast cancer receiving aromatase inhibitor therapy.

PURPOSE: We assessed bone mineral density (BMD) change with aromatase inhibitor (AI) treatment in a contemporary cohort of women with breast cancer treated in Kaiser Permanente Northern California. METHODS: Percent and estimated annual percent changes in BMD at the total hip and lumbar spine were examined in 676 women receiving AI therapy who had two serial BMD reports available (at least 1 year apart) before and after AI initiation (N = 317) or during continued AI therapy (N = 359). BMD changes were examined at the total hip and lumbar spine and compared by age and clinical subgroups. RESULTS: Women experienced BMD declines after AI initiation or continued therapy, with median annual percent change - 1.2% (interquartile range, IQR - 2.4 to - 0.1%) at the hip and - 1.0% (IQR - 2.3 to 0.1%) at the spine after AI initiation, and - 1.1% (IQR - 2.4 to 0.1%) at the hip and - 0.9% (IQR - 2.4 to 0.5%) at the spine during continued therapy. Higher levels of bone loss were observed among younger (< 55 years) compared with older (≥ 75 years) women at the hip (- 1.6% vs. - 0.8%) and at the spine (- 1.5% vs. - 0.5%) after AI initiation, and at the hip (- 1.4% vs. - 1.2%) and at the spine (- 2.4% vs. - 0.001%) during continued therapy. CONCLUSIONS: Small but consistent declines in total hip and lumbar spine BMD were present in breast cancer patients following AI therapy initiation or continued AI therapy. Although the overall rates of osteoporosis were low, greater estimated levels of annual bone loss were evident among women < 55 years.

Genetic Ancestry Is not Associated with Breast Cancer Recurrence or Survival in U.S. Latina Women Enrolled in the Kaiser Permanente Pathways Study.

Background: The U.S. Hispanic/Latino population is heterogeneous both socioculturally and by the proportion of European, Indigenous American, and African ancestry of the regions from which individuals originate. A previous study reported that genetic ancestry was associated with breast cancer survival among Latinas, independent of sociodemographic and tumor characteristics, suggesting that a genetic factor associated with ancestry may affect breast cancer survival.Methods: We evaluated the association of genetic ancestry with breast cancer outcomes among 506 Latina women with invasive breast cancer in the Pathways Study, a cohort study within Kaiser Permanente, an integrated health care delivery system. Proportional hazards models were used to assess the effect of ancestry on breast cancer recurrence (53 events), breast cancer-specific mortality (31 events) and all-cause mortality (54 events), with a mean follow-up time of 6 years.Results: Indigenous American ancestry was not associated with breast cancer recurrence [HR = 1.00 per 10% increase; 95% confidence interval (CI), 0.86-1.16], breast cancer mortality (HR = 0.95; 95% CI, 0.77-1.17), or all-cause mortality (HR = 0.93; 95% CI, 0.80-1.08). Adjustment for sociodemographic variables, tumor characteristics, and treatment did not alter the associations.Conclusions: Our results suggest that previously reported differences in breast cancer survival by genetic ancestry may be overcome by improving health care access and/or quality.Impact: Improving health care access and quality may reduce breast cancer disparities among U.S. Latinas. Cancer Epidemiol Biomarkers Prev; 26(9); 1466-9. ©2017 AACR.

On-site nutrient recovery and removal from source-separated urine by phosphorus precipitation and short-cut nitrification-denitrification.

Source separation and treatment of human urine have been recognized as a resource-efficient alternative to conventional urban drainage, not only reducing nutrient loads on municipal wastewater treatment plants, but recovering valuable resources from waste streams. In this work, on-site phosphorus (P) recovery from real urine was carried out by using the brine from a reverse osmosis process as the flush water for urine-diverting toilets and a P precipitant, while nitrogen (N) was removed via short-cut nitrification-denitrification (SCND) in a membrane bioreactor (MBR). More than 90% of P was recovered by mixing the urine with reverse osmosis brine (1:1, v/v) under the condition of pH > 9.0. The recovered precipitates contained 10-15% of P and can potentially be reused for phosphate fertilizer production. Stable SCND was achieved in a MBR, and 45% of N was removed with the organic compounds in urine as the electron donor for denitrification. Methanol addition significantly elevated denitrification, which in turn replenished the alkalinity required for nitrification. More than 99% of P, 90% of organics and 90% of N were removed in the combined precipitation and MBR process. Nitrosomonas was observed to be the predominant ammonium-oxidizing bacteria, while nitrite-oxidizing bacteria (NOB) were absent in the microbial communities as revealed by fluorescence in situ hybridization and pyrosequencing technique. High concentrations of free ammonia and nitrite acids, as well as low dissolved oxygen, are the prevailing factors to inhibit the growth of NOB, which allows for stable operation of SCND in the MBR.

Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

PURPOSE: The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. METHODS: In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. RESULTS: The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. CONCLUSIONS: Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study.

IMPORTANCE: There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. OBJECTIVE: To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis. DESIGN, SETTING, AND PARTICIPANTS: The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015. MAIN OUTCOMES AND MEASURES: Primary outcomes are breast cancer recurrence, second primary cancer, and death. RESULTS: Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer-specific survival and invasive disease-free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer-specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease-free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment). CONCLUSIONS AND RELEVANCE: Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.

[Effect of Qige Powder on Angiogenesis Induced by Esophageal Cancer Cell Line Eca-9706].

OBJECTIVE: To study the effect Qige powder on esophageal cancer angiogenesis. METHODS: Inhibitive effect of Qige powder ethanol extract on proliferation of Esophageal cancer cell line Eca-9706 was detected by MTT assay. The Eca-9706 cells conditioned medium in Qige powder IC50 concentration were collected. Angiogenesis, as well as proliferation, migration and tube formation of human umbilical vein endothelial cells were observed by Chick embryo chorioallantoic membrane model(CAM), MTT assay, the migration and tube formation assay. VEGF and IL-6 contents in culture medium supernatant of Eca-9706 cells and human umbilical vein endothelial cells were detected by ELISA. RESULTS: Qige powder ethanol extract could inhibit the proliferation of Eca-9706 cells, with a certain dose-effect relationship, IC50 value was 96 µg/mL. Eca-9706 cells conditioned medium could significantly increase the CAM generating total vessel area, human umbilical vein endothelial cells proliferation,migration and tube formation, while the Eca-9706 cell conditioned medium of Qige powder ethanol extract could reduce CAM angiogenesis, human umbilical vein endothelial cells proliferation and tube formation, but increase endothelial cells migration. Qige powder ethanol extract could reduce endothelial cells secreting VEGF and IL-6 while increase Eca-9706 cells secreting. CONCLUSION: Qige powder ethanol extract can inhibit angiogenesis, endothelial cell proliferation, and tube formation induced by Eca-9706 cells, while reduce VEGF and IL-6 secretion of endothelial cells.

[Clinical research of medicinal vesiculation for perennial allergic rhinitis].

OBJECTIVE: To compare the efficacy differences between dog-days medicinal vesiculation and regular-day medicinal vesiculation for perennial allergic rhinitis (PAR), and observe their effects on serum immune globulin E (IgE) and interleukin-4 (IL-4). METHODS: Seventy-two patients were randomly divided into a dog-days moxibustion group (34 cases) and a regular-day moxibustion group (38 cases). In the dog-days moxibustion group, medicinal vesiculation was applied on the 1st dog-day, 2nd dog-day and last dog-day in summer by lunar calendar, 3 treatments per dog-day for totally 9 times. In the regular-day moxibustion group, the moxibustion was given on the regular day for continuous 9 times. The symptom score, rhinoconjunctivitis quality of life questionnaire (RQLQ) and the level of IgE and IL-4 were compared before and after treatment in two groups; the short-term and two-year efficacy evaluation were performed too. RESULTS: The short-term total effective rate was 88.2% (30/34) in the dog-days moxibustion group, which was not significantly different to 86.8% (33/38) in the regular-day moxibustion group (P>0.05). The long-term total effective rate was 97.1% (33/34) in the dog-days moxibustion group, which was significantly superior to 81.6% (31/38) in the regular-day moxibustion group (P<0.05). After treatment, the serum IgE, IL-4 and RQLQ were significantly reduced (all P<0.01), but the difference between two groups was not significant (all P>0.05). CONCLUSION: Medicinal moxibustion could be taken as a regular treatment for PAR, which could be performed during the whole year, and dog-days moxibustion could be considered as an enhanced method for prevention and treatment of PAR.