All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits.

BACKGROUND: The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). METHODS: We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. RESULTS: Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. DISCUSSION: By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.

Medical nutrition treatment of women with gestational diabetes mellitus by a telemedicine system based on smartphones.

AIM: To explore whether WeChat platform-based treatment of women with gestational diabetes mellitus (GDM) reduces the risk of perinatal complications and explore factors affecting gestational age at delivery. METHODS: Pregnant women with GDM (n = 107) and normal glucose tolerance (n =50, group C) according to oral glucose tolerance test (OGTT) results during gestational weeks 24-28 were included. Women with GDM were divided into groups A (n =57) and B (n =50) according to informed consent. According to GDM treatment norms, group B was given routine outpatient treatment and health education guidance. In addition to the interventions in group B, group A was given access to both a smartphone-based telemedicine system and articles providing continuous health education. The PBG level in groups A and B was compared, as were differences in maternal and fetal outcomes. Data were analyzed by t-test, analysis of variance (anova), chi-square test and multiple linear regression, with P < 0.05 considered significant. RESULTS: Fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG) were significantly lower and premature delivery was significantly less likely in group A than in group B (all P < 0.05). Compared with group B, caesarean section was more likely in group A (P < 0.05). Pregnancy-induced hypertension had a higher incidence in group B than in group C (P < 0.05). Gestational age at delivery was associated with OGTT2h, premature fetal membrane rupture and self-monitoring of blood glucose. CONCLUSION: GDM treatment based on the WeChat platform effectively reduces FBG and 2-h PBG and may improve pregnancy outcomes. However, 1-h PBG was not affected by treatment. Obstetricians should consider the OGTT2h value to increase gestational age at delivery.

MAGI3 Suppresses Glioma Cell Proliferation via Upregulation of PTEN Expression.

OBJECTIVE: To investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation. METHODS: The expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA). RESULTS: Expression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples. CONCLUSION: The loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

An increase in alveolar fluid clearance induced by hyperinsulinemia in obese rats with LPS-induced acute lung injury.

A lower mortality rate is observed in obese patients with acute lung injury (ALI), which is referred to as the obesity paradox, in several studies and recent meta-analyses. Hyperinsulinemia is characterized as the primary effect of obesity, and exogenous insulin attenuates LPS-induced pulmonary edema. The detailed mechanism responsible for the effect of hyperinsulinemia on pulmonary edema and alveolar filling needs to be elucidated. SD rats were fed with a high-fat diet (HFD) for a total of 14 weeks. SD rats were anesthetized and intraperitoneally injected with 10 mg/kg lipopolysaccharide (LPS), while control rats received only saline vehicle. Insulin receptor antagonist S961 (20 nmol/kg) was given by the tail vein and serum, and glucocorticoid-induced protein kinase-1 (SGK-1) inhibitor EMD638683 (20 mg/kg) was administrated intragastrically prior to LPS exposure. The lungs were isolated for the measurement of alveolar fluid clearance. The protein expression of epithelial sodium channel (ENaC) was detected by Western blot. Insulin level in serum was significantly higher in HFD rats compared with normal diet rats in the presence or absence of LPS pretreatment. Hyperinsulinemia induced by high fat feeding increased alveolar fluid clearance and the abundance of α-ENaC, ß-ENaC, and γ-ENaC in both normal rats and ALI rats. Moreover, these effects were reversed in response to S961. EMD638683 prevented the simulation of alveolar fluid clearance and protein expression of ENaC in HFD rats with ALI. These findings suggest that hyperinsulinemia induced by obesity results in the stimulation of alveolar fluid clearance via the upregulation of the abundance of ENaC in clinical acute lung injury, whereas theses effects are prevented by an SGK-1 inhibitor.

The viable Mycobacterium tuberculosis H37Ra strain induces a stronger mouse macrophage response compared to the heat-inactivated H37Rv strain.

Macrophages are the target cells for Mycobacterium tuberculosis (M. tuberculosis) as well as key effector cells for clearance of this pathogen. The aim of the present study was to measure and compare the responses of mouse peritoneal macrophages following exposure to the live M. tuberculosis H37Ra and heat-inactivated H37Rv strains. In vitro phagocytosis assays indicated that the macrophages had a higher capacity to engulf the live H37Ra strain compared to the inactivated H37Rv strain. Enzyme-linked immunosorbent assay (ELISA) demonstrated that H37Ra­stimulated macrophages produced significantly increased concentrations of interleukin­12p40 (IL­12p40), tumor necrosis factor-α (TNF­α) and interferon­Î³ (IFN­Î³) compared to the untreated control cells. However, H37Rv exposure induced little to no increase in the levels of the cytokines examined. The results from ELISA were confirmed by reverse transcription-polymerase chain reaction (RT­PCR) at the mRNA level. There was a dose-dependent increase in nitric oxide (NO) and hydrogen peroxide (H2O2) production from the H37Ra­stimulated macrophages compared to the H37Rv­stimulated ones. Confocal microscopy and flow cytometric analysis indicated that the IFN­Î³­stimulated macrophages from viable H37Ra­immunized mice had an enhanced surface expression of CD40 ligand (CD40L) compared to those from inactivated H37Rv­immunized mice. Our data collectively indicate that exposure to the viable H37Ra strain induces a stronger macrophage response compared to exposure to the heat-inactivated H37Rv strain, which may be associated with the increased surface expression of CD40L in activated macrophages.