CT-Measured Angulation Between the Frontal Bone and Bony Nasolacrimal Duct: Variations in Obstructed and Healthy Lacrimal Ducts.

PURPOSE: The aim of this study was to analyze the characteristics of CT-measured intersection angle (FB-BNLD) between the frontal bone and bony nasolacrimal duct and to provide suggestions for treating primary acquired nasolacrimal duct obstruction (PANDO) patients in West China. METHODS: Three hundred and nine participants' CT were, respectively, evaluated with RadiAnt DICOM Viewer. We defined the FB-BNLD angle >0° as the anterior type and the FB-BNLD angle ≤0° as the posterior type. RESULTS: The mean FB-BNLD was -2.52° (95% CI, -3.16° to -1.88°) across all participants, of whom 37.2% were of the anterior type and 62.8% of the posterior type. Approximately 65.0% of the female patients had a posterior FB-BNLD type, and 54.2% of the male patients had an anterior FB-BNLD type (p = .002). Posterior FB-BNLD was the dominant type in the PANDO and control groups (p = .011), and the angle of FB-BNLD was statistically different in both groups (PANDO group, -2.54° to -0.71°; control group, -4.42° to -2.67°; p < .001). Among the male participants, the type of FB-BNLD differed between the two groups (p = .036), with differences in the angle of FB-BNLD (PANDO group, 0.59° to 5.13°; control group, -4.08° to 1.89°; p = .034). There was no difference in the type of FB-BNLD in female participants between the two groups (p = .051). CONCLUSION: The present study revealed individual differences in the type of FB-BNLD, with anterior-type majority in males and posterior-type dominance in females. Evaluating the FB-BNLD type on CT can provide a fast method for knowing the nasolacrimal duct condition during planning for lacrimal manipulation.

BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP.

Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that thioredoxin-interacting protein (TXNIP) is a novel BCR-ABL target gene. Suppression of TXNIP was responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provided a novel survival pathway for the transformation of mouse bone marrow cells. Knockout of TXNIP accelerated BCR-ABL transformation, whereas TXNIP overexpression suppressed this transformation. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.

Analysis of Prognostic Factors of Rectal Cancer and Construction of a Prognostic Prediction Model Based on Bayesian Network.

Background: The existing prognostic models of rectal cancer after radical resection ignored the relationships among prognostic factors and their mutual effects on prognosis. Thus, a new modeling method is required to remedy this defect. The present study aimed to construct a new prognostic prediction model based on the Bayesian network (BN), a machine learning tool for data mining, clinical decision-making, and prognostic prediction. Methods: From January 2015 to December 2017, the clinical data of 705 patients with rectal cancer who underwent radical resection were analyzed. The entire cohort was divided into training and testing datasets. A new prognostic prediction model based on BN was constructed and compared with a nomogram. Results: A univariate analysis showed that age, Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), Carbohydrate antigen 125 (CA125), preoperative chemotherapy, macropathology type, tumor size, differentiation status, T stage, N stage, vascular invasion, KRAS mutation, and postoperative chemotherapy were associated with overall survival (OS) of the training dataset. Based on the above-mentioned variables, a 3-year OS prognostic prediction BN model of the training dataset was constructed using the Tree Augmented Naïve Bayes method. In addition, age, CEA, CA19-9, CA125, differentiation status, T stage, N stage, KRAS mutation, and postoperative chemotherapy were identified as independent prognostic factors of the training dataset through multivariate Cox regression and were used to construct a nomogram. Then, based on the testing dataset, the two models were evaluated using the receiver operating characteristic (ROC) curve. The results showed that the area under the curve (AUC) of ROC of the BN model and nomogram was 80.11 and 74.23%, respectively. Conclusion: The present study established a BN model for prognostic prediction of rectal cancer for the first time, which was demonstrated to be more accurate than a nomogram.

[Lipopolysaccharide induces inflammation and up-regulates the expression of methyltransferase-like 3 (METTL3) and METTL14 in human and mouse intestinal epithelial cells].

Objective To investigate the changes of N6-methyladenosine (m6A) modification in the inflammatory status of HIEC-6 human intestinal epithelial cells and MODE-K mouse intestinal epithelial cells. Methods HIEC-6 cells and MODE-K cells were induced by different concentrations of lipopolysaccharide (LPS), interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor alpha (TNF-α) for 10 hours or the same concentration of LPS, IL-1ß, IL-6 and TNF-α for 0, 3, 6, 12, 24 hours, respectively. The mRNA expression levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were detected by real-time quantitative PCR. The mRNA and protein expression levels of m6A modification-related molecules methyltransferase-like 3 (METTL3), METTL14, METTL16, Wilm's tumor 1-associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), fat-mass and obesity-associated protein (FTO), YTH domain-containing 1 (YTHDC1), YTHDC2 were detected through real-time quantitative PCR and Western blot, respectively. Results The mRNA expression levels of IL-1ß, IL-6 and TNF-α were increased and the mRNA and protein expression levels of METTL3 and METTL14 were simultaneously up-regulated in time-dependent and concentration-dependent LPS-induced model in HIEC-6 cells and MODE-K cells. Conclusion LPS can induce inflammation and up-regulate the expression of METTL3 and METTL14 in intestinal epithelial cells.

Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression.

AIMS: Discs large-associated protein 5 (DLGAP5), a kinetochore fibers-binding protein, functions as a oncoprotein in many cancers. However, its expression patterns in pan-cancer including clear cell renal cell carcinoma (ccRCC) are not analyzed. Herein, we aimed to evaluate its expression in more common cancers, especially in ccRCC. MAIN METHODS: Data from Genotype-Tissue Expression, The Cancer Genome Atlas, and Tumor Immune Estimation Resource were used to analyze the DLGAP5 expression in normal tissues, cancer cell lines, and cancer tissues, as well as the immune infiltration levels. The analysis results were verified with ccRCC cell lines via RNAi, western blotting, and the cytological analysis. KEY FINDINGS: Low DLGAP5 expression in 31 types of normal tissues, the upregulation in 21 cancer cell lines, and the significant elevated expression in 26 types of cancers, were found, Surprisingly, kidney cancer including ccRCC, DLGAP5 exhibited a slightly elevated but statistically significant expression among 26 types of cancers. In addition, elevated DLGAP5 expression was significantly positive correlated with immune infiltration level in ccRCC. The survival probability of some cancers including kidney cancer, clinical TNM stage of ccRCC patients were significantly related to upregulated DLGAP5 expression. The experiments results showed DLGAP5 upregulation in ccRCC tissues and the cell lines, its knockdown inhibited the cells viability and proliferation, and compromised the cells migration and invasion. SIGNIFICANCE: Elevated DLGAP5 expression occurred in common cancers. However, its slightly upregulated expression is related with ccRCC progression, it is therefore a prognostic risk factor for ccRCC, but not an independent factor.

miR-335-5p suppresses gastric cancer progression by targeting MAPK10.

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

[Analysis of X-Ray Fluorescence Spectroscopy and Plasma Mass Spectrometry of Pangxidong Composite Granitoid Pluton and Its Implications for Magmatic Differentiation].

Pangxidong composite granitoid pluton located in the southwestern margin of Yunkai massif. The metamorphic grade of this pluton increases from outside to inside, that is, banded-augen granitic gneisses, gneissoid granites and granites distribute in order from edge to core. X-Ray Fluorescence Spectroscopy and Plasma Mass Spectrometry are conducted to study the geochemical characteristics of the three types of rocks. The result shows that all the three types of rocks are peraluminous rocks and their contents of main elements and rare earth elements change gradually. From granitic gneisses to granites, the contents of Al2O3, CaO, MgO, TiO2, total rare earth elements and light rare earth elements increase, but the contents of SiO2 and heavy rare earth elements decrease. It is suggested that the phylogenetic relationship exists between granitic gneisses, gneissoid granites and granites during the multi-stage tectonic evolution process. Furthermore, the remelting of metamorphosed supracrustal rocks in Yunkai massif is probably an important cause of granitoid rocks forming. The evolutionary mechanism is probably that SiO2 and heavy rare earth elements were melt out from the protolith and gradually enriched upward, but Al2O3, CaO, MgO, TiO2 and light rare earth elements enriched downward.