Objectives
To identify clinicopathologic and ultrasound (US) variables that were associated with a heavy nodal tumor burden, which was defined as 3 or more lymph nodes involved with metastasis to the ...axilla after invasive breast carcinoma.
Methods
With ethical approval, 621 patients with a pathologic diagnosis of invasive breast carcinoma were retrospectively analyzed for clinical, pathologic, and US data. Pathologic findings were ascertained by the final paraffin pathologic analysis. Ultrasound characteristics were evaluated on the basis of the American College of Radiology's Breast Imaging Reporting and Data System (BI‐RADS). Univariate and multivariate logistic regression analyses were used to assess the clinicopathologic and US variables that were associated with a heavy nodal tumor burden at the axilla.
Results
There were 107 cases (17.2%) of invasive breast carcinoma with a heavy tumor burden at the axilla. The independent clinicopathologic variables for a heavy tumor burden at the axilla included a tumor size of 2 to 5 cm (odds ratio OR, 1.86; P = .036), the presence of lymphovascular invasion (OR, 23.52; P < .001), the presence of papillary invasion (OR, 2.93; P = .043), and a non–triple‐negative subtype (OR, 2.34; P = .04). The independent US features of breast tumors that were associated with a heavy tumor burden at the axilla included BI‐RADS category 5 (OR, 5.50; P = .024) and a posterior acoustic shadow (OR, 1.94; P = .024).
Conclusions
A large tumor size, lymphovascular invasion, papillary invasion, and a non–triple‐negative subtype on the pathologic analysis as well as BI‐RADS category 5 and a posterior acoustic shadow on a US assessment were associated with a heavy nodal tumor burden at the axilla. These US characteristics of the primary breast carcinoma might provide additional information to axillary US for the prediction of axillary nodal tumor loads.
To evaluate the feasibility and clinical value of three-dimensional ultrasound in evaluating ovarian function in perimenopausal women. In this prospective cohort study, 102 patients with clinically ...suspected perimenopause and 90 patients with menopause were enrolled. These patients were classified into three groups according to the level of follicle stimulating hormone (FSH) and estradiol (E2): menopause group, perimenopause group, and normal group. Perimenopause group: There were significant differences in volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in the ovaries after treatment. Cycle 1 > cycle 0 (p < .05) and cycle 3 <cycle 0 (p < .05) in FSH. Menopause group: There were significant differences in volume, VI, FI, and VFI of the ovaries after treatment: Cycle 3 >cycle 0 (p < .05), and in FSH: cycle 3 < cycle 0 (p < .05). Three-dimensional ultrasound in ovarian quantitative measurement can objectively reflect the change in the ovarian function, predicting the effect of drug treatment, and provided an objective information for early intervention to menopausal.
AIM： TO study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury. METHODS： Wistar rats were used in this study. A gastric mucosal injury model was ...established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde （MDA） in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase （ATPase） subunits 6 and 8 in mitochondrial DNA （mtDNA） was determined by reverse transcription polymerase chain reaction （RTPCR）. RESULTS： The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and the exposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol. CONCLUSION： Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.
Aim： To investigate whether AMP-activated protein kinase （AMPK） regulates the expression of pancreatic duodenal homeobox-1 （PDX- 1）, a β-cell-specific transcription factor and whether PPARa/γ is ...involved in the regulation of pancreatic β-cell lines after acute stimula- tion. Methods： Rat insulinoma cell line INS-1 was treated with an activator （AICAR） or inhibitor （Compound C） of AMPK as well as inhibitors of PPARs （MK886 to PPARα and BADGE to PPARy）. The mRNA levels of PDX-1, PPARa and PPARy were measured using real-time RT- PCR, and Western blotting was used to detect the protein expression of these factors. Results： Activation of AMPK by AICAR induced significantly increased the expression of PDX-1, and this increase was abrogated when AMPK was inactivated by Compound C. Similarly, the expression of PPARα and PPARy was also increased by AICAR or decreased by Compound C. However AMPK activation did not increase nuclear PDX-1 protein levels when PPARa was inhibited. In contrast, AMPK activation still up-regulated PDX-1 protein levels during PPARy inhibition. Additionally, PPARα activation induced by fenofibrate signifi- cantly enhanced nuclear PDX-1 protein expression. Conclusion： AMPK regulates the expression of PDX-1 at both the transcriptional and protein levels, and PPARα may be acutely involved in the regulation of INS-1 cells.
The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS).
A ...total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests.
The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts.
In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.
Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational ...mechanisms remain fully elucidated.
The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM.
Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein-protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs).
The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including
and
. For the characteristic Aβ and Tau pathology of AD,
was associated significantly positively with AD and
significantly negatively with AD. In addition, we also found
and
significant correlations with DM phenotypes. Other datasets verified that
,
,
and
could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases.
The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.
Iron (Fe) isotope fractionation could occur during crustal melting, which may contribute to the isotopic variations of granites. Our current knowledge on Fe isotope fractionation during crustal ...melting remains rare. Thirteen leucosomes, 9 melanosomes and 1 amphibolitic schollen in 11 migmatites from the Dabie orogen, Central China were measured to investigate Fe isotope fractionation during crustal anatexis. The melanosomes and amphibolitic schollen yield δ56Fe values from 0.018±0.031‰ to 0.152±0.027‰ with an average of 0.106‰. The leucosomes have δ56Fe values from 0.107±0.035‰ to 0.512±0.028‰, variably higher than their coexisting melanosomes by 0.00~0.36‰. The δ56Fe of leucosomes and melanosomes, as well as apparent isotope fractionation (Δ56FeL-M) between them, do not correlate with the abundance of crystalline carbonate, loss on ignition, and Th/U, indicating the insignificant effect of fluid components. High δ56Fe values of three leucosomes (≥0.34‰), giving large Δ56FeL-M from 0.22 to 0.36‰, were likely produced by feldspar accumulation, evidenced by their high Eu*, low FeOt/Al2O3 and high plagioclase abundance up to 50vol%. Capture of peritectic amphiboles in another leucosome may explain its low Δ56FeL-M ~0‰. After screening out these samples, 7 leucosome – melanosome pairs yield identical Δ56FeL-M averaging 0.093±0.056‰ (2SD, N=7) within analytical uncertainties. No correlation between Δ56FeL-M and Mg#, FeOt/Al2O3 or TiO2/FeOt rules out the possibility that the fractionation observed here is produced by fractional crystallization and/or sub-solidus isotope re-equilibrium between leucosomes and melanosomes. Therefore, we suggest these consistent Δ56FeL-M should record equilibrium Fe isotope fractionation during crustal anatexis producing these migmatites. The leucosomes and melanosomes have comparable Fe3+/ΣFe~0.40, and Δ56FeL-M approximates 0.07‰ at Fe3+/ΣFeleucosomeFe3+/ΣFemenalosome=1. Fe isotope fractionation during crustal anatexis revealed here thus is not dominantly controlled by distribution of Fe3+ and Fe2+, but by the difference in coordination number of iron between granitic melts and residual mafic minerals. The observation here argues that Fe isotope fractionation during crustal partial melting should also contribute to the previously revealed δ56Fe variation in high silica granitic rocks.
•Detectable Fe isotope fractionation ~0.09‰ occurs during crustal anatexis.•The isotope fractionation (IF) is not controlled by distribution of Fe3+ and Fe2+.•The IF reflects the difference in FeO bonding between the melts and residua.•The IF during crustal melting contributes to the δ56Fe variation of granites.
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Chemoresistance has been a major reason for the drug therapy failure. The present study ...performed a microarray analysis between MCF‑7 and MCF‑7/adriamycin (ADR) cells, and intended to identify long non‑coding (lnc)RNA expression character in drug resistant breast cancer cells. MCF‑7/ADR cells were induced from MCF‑7 cells via pulse‑selection with doxorubicin for 4 weeks, and the resistance to doxorubicin of ADR cells was confirmed by MTT assay. Microarray analysis was performed between MCF‑7 and MCF‑7/ADR cells. Total RNA was extracted from the two cell lines respectively and was transcribed into cDNA. The results of the microarray were verified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Gene Ontology (GO) and pathways analysis were conducted to enrich the dysregulated lncRNAs presented in the microarray results. Compared to the MCF‑7 cells, 8,892 lncRNAs were differentially expressed in MCF/ADR cells (absolute fold‑change >2.0). A total of 32 lncRNAs were selected for RT‑qPCR by fold‑change filtering, standard Student's t‑test, and multiple hypothesis testing. Among the dysregulated lncRNAs, AX747207 was prominent because its associated gene RUNX3 was previously reported to be relative to malignant tumor chemoresistance. GO analysis results also indicated some biological processes and molecular functions linked to chemoresistance. The pathway enrichment results provided some potential pathways associated with chemoresistance. In the present study, the authors intended to identify lncRNA expression character in drug resistant cell line MCF‑7/ADR, corresponding to the parental MCF‑7 cell line. In addition, the study identified the lncRNA AX747207, and its potential targeted gene RUNX3, may be related to chemoresistance in breast cancer. These results may new insights into exploring the mechanisms of chemoresistance in breast cancer.
In the title compound, C18H15ClFN3O4, the dihedral angle between the substituted pyridine ring and the oxadiazoline ring is 9.73 (19)° and the acyl group is coplanar with the oxadiazoline ...ring O—C—N—C torsion angle = −2.1 (3)°. Furthermore, the substituted benzene ring is almost orthogonal with the oxadiazoline ring, the dihedral angle between them being 87.56 (18)°.
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