A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Effect of low-dose lanthanum carbonate on calcium and phosphorus metabolism in Asian Patients with end-stage renal disease, maintenance hemodialysis and hyperphosphatemia.

Objective: This study aimed to examine whether a 12-week small-dose lanthanum carbonate (LaCO3; 500 mg/d) treatment could improve calcium and phosphorus metabolism and parathyroid function in Asian patients with end-stage renal disease (ESRD) under hemodialysis. Methods: This was a prospective observational study of patients treated at our Hospital between 10/2014 and 02/2015. The patients were given 500 mg/d of LaCO3 with lunch for 12 weeks. Results: Baseline and after 12-week treatment serum phosphorus levels were 2.49±0.51 mmol/L and 1.65±0.34 mmol/L (P<0.001). The baseline and after 12-week treatment calcium×phosphorus product were 69.40±17.34 mg2/dL2 and 44.27±9.67 mg2/dL2 (P<0.001). There was no significant difference in serum calcium and iPTH levels from baseline to after 12 weeks treatment (both P>0.05). Fourteen (25.9%) patients developed gastrointestinal adverse reactions to LaCO3 and 10 patients improved after treatment. Conclusion: Far below the 1.5-3.0g/d required by the drug instructions, LaCO3 500 mg/d for 12 weeks can still reduce serum phosphorus level and calcium × phosphorus product, without serum calcium and iPTH levels increase.

CTHRC1 is a Potential Prognostic Biomarker and Correlated with Macrophage Infiltration in Breast Cancer.

Background: Tumor immune cell infiltration is closely associated with the occurrence and development of tumors. Collagen triple helix repeats containing 1 (CTHRC1), a regulator of collagen expression and cell migration, is involved in the metastasis and invasion of tumors. However, the role of CTHRC1 in breast cancer remains unclear. This study aimed to investigate the prognostic value of CTHRC1, and further explore its association with immune infiltration in breast cancer. Methods: CTHRC1 expression pattern and prognostic value were analyzed using ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter databases. We then detected CTHRC1 mRNA levels in breast cancer tissues and paired normal breast tissues by Q-PCR. Subsequently, the University of California Santa Cruz (UCSC) database was used to determine the methylation status of CTHRC1. Furthermore, CTHRC1 mutations were investigated using the Catalogue of Somatic mutations in Cancer (COSMIC) and cBioPortal databases. We also assessed the correlation between CTHRC1 expression and immune cell infiltration using TIMER. In addition, The relationship of CTHRC1 expression with the immune marker sets of various immune cells was evaluated using GEPIA and TIMER. Results: CTHRC1 was highly expressed in a variety of tumors, including breast cancer. Elevated CTHRC1 expression was related to a poor prognosis. Notably, CTHRC1 expression was significantly associated with macrophage infiltration, especially the immune infiltration gene marker set of M2. Copy number variations, DNA mutations and methylation states might be potential mechanisms for regulating CTHRC1 expression. Protein digestion and absorption, human papillomavirus infection, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways were identified as the potential CTHRC1-driven signaling pathways. Conclusion: These findings suggest that CTHRC1 could be a promising immune-related biomarker for the treatment of breast cancer patients.

Hyperuricemia is Related to the Risk of Cardiovascular Diseases in Ethnic Chinese Elderly Women.

Background: The association between hyperuricemia (HUA) and cardiovascular diseases (CVDs) is not fully elucidated. Objective: To assess the relationship according to factors of sex and age in the Chinese ethnic groups. Methods: We performed a population-based cross-sectional study in a multi-ethnic population from southwestern China. HUA patients were identified by serum uric acid ≥7 mg/dL in men and 6 mg/dL in women. The outcome was composite prevalent CVDs, including coronary heart disease (CHD), stroke, and arrhythmia. Multivariate logistic regression analysis, estimating odds ratio (ORs) and 95% confidence intervals (CIs), were applied to evaluate the HUA-CVDs relationship. Results: We included 16,618 people (37.48% Dong, 30.00% Miao, and 32.52% Bouyei) aged 30-79 years without a reduced estimated glomerular filtration rate <60 mL/min/1.73 m2. CVDs developed in 250 Dong, 196 Miao, and 205 Bouyei adults. Among women, HUA was positively associated with the risk of stroke in Dong ethnicity and CVDs in Bouyei ethnicity (ORs (95% CIs) 2.02 (1.07-3.81) and 1.66 (1.06-2.59)) compared with non-HUA. In the age-specific analysis, HUA was related to the risk of CVDs (OR 2.32, 95% CI 1.00-5.38) and CHD (5.37, 1.61-17.89) among Miao people aged < median age, CVDs (1.52, 1.11-2.08) and stroke (1.67, 1.02-2.72) among Dong adults aged ≥ median age, and CVDs (1.67, 1.16-2.40) and CHD (1.77, 1.13-2.77) among Bouyei ethnicity aged ≥ median age. After stratification by sex and the median age, for women aged > 50 years, a 55% (1.55, 1.00-2.39) and 65% (1.65, 1.02-2.66) increased risk for CVDs was observed in Dong and Bouyei ethnicities. Conclusions: HUA may be related to an increased risk of CVDs among women in the Dong and Bouyei ethnic groups in China, especially women aged > 50 years.

Resting heart rate is associated with the risk of metabolic syndrome and its components among Dong adults in southwest China: Cross-sectional findings of the China Multi-Ethnic Cohort Study.

AIMS: High resting heart rate (RHR), one abnormal manifestation of autonomic nervous system, is associated with metabolic disorders. However, the association between RHR and metabolic syndrome (MetS) and its components remains controversial. We aimed to explore the link between these two parameters. MATERIALS AND METHODS: The study included 6589 Dong adults (1434 cases of MetS) from the cross-sectional survey of the China Multi-Ethnic Cohort Study. Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and assess the association between RHR and MetS, clustered metabolic risk, and MetS components. Restricted cubic splines model was used to evaluate the dose response association. RESULTS: A positive association existed between RHR and MetS, and people in the highest RHR quartile had a higher MetS risk (OR 1.75 [95% CI 1.42-2.15]) than those in the lowest quartile. The clustered metabolic risk associated with RHR (p < 0.05). Furthermore, RHR was related to elevated blood pressure (BP), elevated triglycerides (TG) and elevated fasting plasma glucose (FPG); the ORs (95% CIs) for the highest versus lowest RHR quartile were 2.06 (1.75-2.43), 1.37 (1.17-1.62) and 2.53 (2.04-3.14), respectively. Similar results were found in sensitivity and subgroup analyses. Also, non-linear dose response association existed between RHR and MetS and elevated levels of BP, TG and FPG (p < 0.001). CONCLUSIONS: RHR was related to increased risk of MetS, three MetS components (elevated BP, elevated TG and elevated FPG) and the clustered metabolic risk. RHR may be a useful indicator for MetS.

Family History of Hypertension and Cobalt Exposure Synergistically Promote the Prevalence of Hypertension.

It has been previously reported that family history of hypertension (FHH) and exposure to metals are each independent risk factor for hypertension, but the interaction between the two in relation to hypertension risk has been poorly studied. The object of this study is Dong ethnic group in Guizhou, China. The impacts of exposure to metals and FHH on hypertension incidence were examined by using the restrictive cubic spline (RCS) model as well as the multivariate logistic regression model. As a result, FHH, together with cobalt and lead exposure, was identified to show independent significant correlation with hypertension incidence (P < 0.05). The risk of hypertension increased with the increase in lead and cobalt exposure quartiles. Typically, the RCS model revealed such dose-response relation. To further confirm the association of cobalt, lead, and FHH with the risk of hypertension, multiplication and addition models were used to analyze the influence of the interactions between these variables on the risk of hypertension. The results showed that there was a multiplying interaction between the influence of the FHH and cobalt on the risk of hypertension. As for the additive interaction between cobalt and FHH, the relative excess risk due to interaction (RERI) was determined to be 0.596 (95% Cl: 0.001-1.191), the attributable proportion due to interaction (AP) was calculated as 0.256 (95% Cl: 0.075-0.437), whereas the synergy index (S) was identified to be 1.814 (95% Cl: 1.080-3.047). Our study provides some limited evidence that a FHH and cobalt exposure synergistically promote the prevalence of hypertension.

Analysis of Threshold Effect of Urinary Heavy Metal Elements on the High Prevalence of Nephrolithiasis in Men.

Exposure to heavy metals in the environment exerts serious effects on kidney health. However, the effects of joint exposure on the kidneys have been rarely studied, particularly in non-occupational exposure high-risk populations. This study provided a reference threshold range of heavy metals in urine and explored the effect of joint exposure on nephrolithiasis in men. The data were obtained from the China Multi-Ethnic Cohort database, and 1502 men were included in the study. A two-piece-wise regression model was used to assess the dose-response relationship between heavy metal exposure and nephrolithiasis. The least absolute shrinkage and selection operator regression model was used to calculate the score of joint exposure to heavy metals. The threshold effect analysis revealed a linear relationship between the concentration of arsenic (As) in the urine and the prevalence of nephrolithiasis, whereas a nonlinear relationship was observed with cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). In addition, As, Cd, Cr, Hg, and Pb may significantly affect the joint exposure effect. Moreover, the final risk of nephrolithiasis increased by 123% (P for trend < 0.001). This study found a threshold relationship between heavy metals (Cd, Cr, Hg, Pb) in male urine and the occurrence of nephrolithiasis. Joint exposure to heavy metals in urine caused a high-risk effect on nephrolithiasis. The study provided a reference threshold value of related studies and indicated that environmental pollution caused by heavy metals should be reduced.

Relationship between different surgical methods, hemorrhage position, hemorrhage volume, surgical timing, and treatment outcome of hypertensive intracerebral hemorrhage.

BACKGROUND: The present study aimed to explore the relationship between surgical methods, hemorrhage position, hemorrhage volume, surgical timing and treatment outcome of hypertensive intracerebral hemorrhage (HICH). METHODS: A total of 1 310 patients, who had been admitted to six hospitals from January 2004 to January 2008, were divided into six groups according to different surgical methods: craniotomy through bone flap (group A), craniotomy through a small bone window (group B), stereotactic drilling drainage (group C1 and group C2), neuron-endoscopy operation (group D) and external ventricular drainage (group E) in consideration of hemorrhage position, hemorrhage volume and clinical practice. A retrospective analysis was made of surgical timing and curative effect of the surgical methods. RESULTS: The effectiveness rate of the methods was 74.12% for 1 310 patients after one-month follow-up. In this series, the disability rate was 44.82% 3-6 months after the operation. Among the 1 310 patients, 241 (18.40%) patients died after the operation. If hematoma volume was >80 mL and the operation was performed within 3 hours, the mortality rate of group A was significantly lower than that of groups B, C, D, and E (P<0.05). If hematoma volume was 50-80 mL and the operation was performed within 6-12 hours, the mortality rate of groups B and D was lower than that of groups A, C and E (P<0.05). If hematoma volume was 20-50 mL and the operation was performed within 6-24 hours, the mortality rate of group C was lower than that of groups A, B and D (P<0.05). CONCLUSIONS: Craniotomy through a bone flap is suitable for patients with a large hematoma and hernia of the brain. Stereotactic drilling drainage is suggested for patients with hematoma volume less than 80 mL. The curative effect of HICH individualized treatment would be improved via the suitable selection of operation time and surgical method according to the position and volume of hemorrhage.