Association of KATP Variants With CMD and RAP in CAD Patients With Increased Serum Lipoprotein(a) Levels.

CONTEXT: Refractory angina pectoris (RAP) is a specific subtype of coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] and its induced coronary microvascular dysfunction (CMD) play an important role in pathogenesis of RAP, but its metabolism was mostly genetically determined. The adenosine triphosphate (ATP)-sensitive potassium channel (KATP) is involved in lipid metabolism and microvascular homeostasis and becomes a promising target for the management of Lp(a) and its related RAP. OBJECTIVE: To investigate associations of KATP variants with hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD. DESIGN, PATIENTS, SETTINGS: A total of 1148 newly diagnosed patients with CAD were prospectively selected and divided into control (Lp(a) < 180 mg/dL) and case (Lp(a) ≥ 180 mg/dL, hyperlipoprotein(a)emia) group. METHODS: 9 KATP variants were genotyped by MassARRAY system. The expression profile of exosome-derived microRNAs (exo-miRs) was identified by next-generation sequencing, and the expression levels of differentially expressed exo-miRs were evaluated by quantitative RT-PCR in verification cohort. RESULTS: Three KATP variants were associated with increased risk of hyperlipoprotein(a)emia in patients with CAD as follows: rs2285676 (AA + GA genotype, adjusted odds ratio [OR] = 1.44; 95% CI, 1.10-1.88; P = 0.008), rs1799858 (CC genotype, adjusted OR = 1.33; 95% CI, 1.03-1.73; P = 0.030), and rs141294036 (CC genotype, adjusted OR = 1.43; 95% CI, 1.10-1.87; P = 0.008). Only rs141294036 was associated with increased risk of CMD (CC genotype, adjusted OR = 1.62; 95% CI, 1.23-2.13; P = 0.001), and further with increased RAP risk (CC genotype, adjusted hazard ratio = 2.05; 95% CI, 1.22-3.43; P = 0.007) after median follow-up of 50.6 months. Between the 2 genotypes of rs141294036, 152 exo-miRs were significantly differentially expressed, but only 10 exo-miRs (miR-7110-3p, miR-548az-5p, miR-214-3p, let-7i-5p, miR-218-5p, miR-128-3p, miR-378i, miR-625-3p, miR-128-1-5p, and miR-3187-3p) were further confirmed in patients with RAP with hyperlipoprotein(a)emia and CMD. CONCLUSION: KATP rs141294036 may serve a potential genetic marker for hyperlipoprotein(a)emia, CMD, and RAP in patients with CAD.

High Uniformity and Enhancement Au@AgNS 3D Substrates for the Diagnosis of Breast Cancer.

Breast cancer appears to be one of the leading causes of cancer-related morbidity and mortality for women worldwide. The accurate and rapid diagnosis of breast cancer is hence critical for the treatment and prognosis of patients. With the vibrational fingerprint information and high detection sensitivity, surface-enhanced Raman spectroscopy (SERS) has been extensively applied in biomedicine. Here, an optimized bimetallic nanosphere (Au@Ag NS) 3D substrate was fabricated for the aim of the diagnosis of breast cancer based on the SERS analysis of the extracellular metabolites. The unique stacking mode of 3D Au@Ag NSs provided multiple plasmonic hot spots according to the theoretical calculations of the electromagnetic field distribution. The low relative standard deviation (RSD = 2.7%) and high enhancement factor (EF = 1.42 × 105) proved the uniformity and high sensitivity. More importantly, the normal breast cells and breast cancer cells could be readily distinguished from the corresponding SERS spectra based on the extracellular metabolites. Furthermore, the clear clusters of SERS spectra from MCF-7 and MDA-MB-231 extracellular metabolites in the orthogonal partial least-squares discriminant analysis plot indicate the distinct metabolic fingerprint between breast cancer cells, which imply their potential clinical application in the diagnosis of breast cancer.

Association of marital status with cardiovascular outcome in patients with breast cancer.

Background: The influences of marital status on cardiovascular death risk in patients with breast cancer remained unclear. This study aimed to evaluate the associations of different marital status with cardiovascular death risk in patients with breast cancer. Methods: A total of 182,666 female breast cancer patients were enrolled in this study from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2014, and was divided into two groups: married (N=107,043) and unmarried (N=75,623). A 1:1 propensity score matching (PSM) was applied to reduce inter-group bias between the two groups. Competing-risks model was used to assess the associations between different marital status and cardiovascular death risk in patients with breast cancer. Results: After PSM, marital status was an independent predictor for cardiovascular death in patients with breast cancer. Unmarried condition was associated with increased cardiovascular death risk than married condition among breast cancer patients [unadjusted model: hazard ratio (HR) =2.012, 95% confidence interval (CI): 1.835-2.208, P<0.001; Model 1: HR =1.958, 95% CI: 1.785-2.148, P<0.001; Model 2: HR =1.954, 95% CI: 1.781-2.144, P<0.001; Model 3: HR =1.920, 95% CI: 1.748-2.107, P<0.001]. With the exception of separated condition (adjusted HR =0.886, 95% CI: 0.474-1.658, P=0.705), further unmarried subgroups analysis showed that the other three unmarried status were associated with increased cardiovascular death risk as follows: single (adjusted HR =1.623, 95% CI: 1.421-1.853, P<0.001), divorced (adjusted HR =1.394, 95% CI: 1.209-1.608, P<0.001), and widowed (adjusted HR =2.460, 95% CI: 2.227-2.717, P<0.001). In particularly, widowed condition showed the highest cardiovascular death risk in all 4 unmarried subgroups. Conclusions: Unmarried condition (e.g., single, divorced and widowed) was associated with elevated cardiovascular death risk compared with their married counterparts in patients with breast cancer, suggesting that more attention and humanistic care should be paid to unmarried breast cancer patients (especially the widowed patients) in the management of female breast cancer patients.

TASP1 Promotes Proliferation and Migration in Gastric Cancer via EMT and AKT/P-AKT Pathway.

Threonine aspartase 1 (TASP1) was reported to function in the development of cancer. However, the regulatory mechanism of TASP1 in gastric cancer (GC) remains unclear. In this study, we determined the expression of TASP1 in tissues of GC patients, GC cells by qRT-PCR, and western blot and assessed the relationship between TASP1 and GC cell proliferation and migration via CCK-8 and transwell assay. It was found that the expression of TASP1 in GC tissues or GC cell lines was significantly higher than that in normal adjacent tissues or normal cells. The proliferation and migration of GC cells were inhibited upon TASP1 knockdown. Mechanism investigation revealed that TASP1 promoted GC cell proliferation and migration through upregulating the p-AKT/AKT expression. TASP1 induced GC cell migration via the epithelial -mesenchymal transition (EMT) pathway. In conclusion, TASP1 promotes GC progression through the EMT and AKT/p-AKT pathway, and it may serve as a new potential biomarker and therapeutic target for GC.

Identification of Driver Genes Regulating the T-Cell-Infiltrating Levels in Hepatocellular Carcinoma.

The driver genes regulating T-cell infiltration are important for understanding immune-escape mechanisms and developing more effective immunotherapy. However, researches in this field have rarely been reported in hepatocellular carcinoma (HCC). In the present study, we identified cancer driver genes triggered by copy number alterations such as CDKN2B, MYC, TSC1, TP53, and GSK3B. The T-cell infiltration levels were significantly decreased in both HCC and recurrent HCC tissues compared with the adjacent normal liver tissues. Remarkably, we identified that copy number losses of MAX and TP53 were candidate driver genes that significantly suppress T-cell infiltration in HCC. Accordingly, their downstream oncogenic pathway, cell cycle, was significantly activated in the low T-cell infiltration HCC. Moreover, the chemokine-related target genes by TP53, which played key roles in T-cell recruitment, were also downregulated in HCC with TP53/MAX deletions, suggesting that copy number losses in MAX and TP53 might result in T-cell depletion in HCC via downregulating chemokines. Clinically, the T-cell infiltration levels and chemokines activity could accurately predict the response of sorafenib, and the prognostic outcomes in HCC. In conclusion, the systematic analysis not only facilitates identification of driver genes and signaling pathways involved in T-cell infiltration and immune escape, but also gains more insights into the functional roles of T cells in HCC.

[Clinical observation on effects of acupuncture at Dazhui (GV 14) for abating fever of common cold].

OBJECTIVE: To explore the therapeutic effect of acupuncture at Dazhui (GV 14) for abating fever of common cold. METHODS: Two hundred and sixty-one cases were randomly assigned to a treatment group of 133 cases and a control group of 128 cases. The treatment group were treated with electroacupuncture at Dazhui (GV 14) and the control group with antondine injection. The transient effect of abating fever within 24 h was observed. RESULTS: After treatment, the body temperature at all observation time points in the treatment group were lower than those in the control group (P < 0.01). The effect-appearing time (1.42 +/- 1.79) h in the treatment group was shorter than that in the control group (3.44 +/- 5.10) h (P < 0.01). The cured rate and the abating fever rate were 27.8% and 75.9% in the treatment group, and 10.9% and 55.5% in the control group, with significant differences between the two groups, the treatment group being better than the control group (P < 0.01). The abating fever rate for the wind-heat type common cold was 75.3% in the treatment group and 50.0% in the control group, with significant difference between the two groups, the treatment group being better than the control group (P < 0.01). CONCLUSION: The method of acupuncture at Dazhui (GV 14) has a definite therapeutic effect on high fever of common cold, and for wind-heat type common cold, Dazhui (GV 14) first may be chosen to abate high-fever and the treatment should be taken as early as possible.