Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

[Recent progress of dry powder inhalation of proteins and peptides].

To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder.

Development and Validation of a Prognostic Nomogram for HR+ HER- Breast Cancer.

Purpose: We aimed to develop a nomogram to predict prognosis of HR+ HER2- breast cancer patients and guide the application of postoperative adjuvant chemotherapy. Methods: We identified 310 eligible HR+ HER- breast cancer patients and randomly divided the database into a training group and a validation group. The endpoint was disease free survival (DFS). Concordance index (C-index), area under the curve (AUC) and calibration curves were used to evaluate predictive accuracy and discriminative ability of the nomogram. We also compared the predictive accuracy and discriminative ability of our nomogram with the eighth AJCC staging system using overall data. Results: According to the training group, platelet-to-lymphocyte ratio (PLR), tumor size, positive lymph nodes and Ki-67 index were used to construct the nomogram of DFS. The C-index of DFS was 0.708 (95% CI: 0.623-0.793) in the training group and 0.67 (95% CI: 0.544-0.796) in the validation group. The calibration curves revealed great consistencies in both groups. Conclusion: We have developed and validated a novel and practical nomogram that can provide individual prediction of DFS for patients with HR+ HER- breast cancer. This nomogram may help clinicians in risk consulting and guiding the application of postoperative adjuvant chemotherapy.

Intramolecular Hydrogen Bonding Rigidifying Flexible Bridge for Solution- and Vacuum-Processed TSCT-TADF Emitters.

To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

The prognostic value of m6A-related LncRNAs in patients with HNSCC: bioinformatics analysis of TCGA database.

N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan-Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.

Real-world outcomes for Chinese breast cancer patients with tumor location of central and nipple portion.

Background: The association between tumor location and breast cancer prognosis has been controversial. We sought to explore the relationship between tumors located in central and nipple portion (TCNP) and Chinese breast cancer. Patients and methods: A total of 1,427 breast cancer patients were recruited. There were 328 cases of TCNP and 1,099 cases of tumors in the breast peripheral quadrant (TBPQ). The chi-square test was used to compare different variables between TCNP and TBPQ groups. A one-to-one propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of TCNP and TBPQ groups. Kaplan-Meier curves were used for survival analysis of disease-free survival (DFS), breast cancer-specific survival (BCSS) and overall survival (OS). The Cox proportional hazards regression model was applied to identify prognostic risk factors. Results: The median follow-up time was 58 months. Compared to TBPQ, TCNP patients had significantly larger tumor size, more frequent metastasis to lymph nodes (LN) and more proportions of TNM stage II-III. DFS, OS and BCSS rates were markedly lower in the TCNP group as compared to the TBPQ group before and after PSM (all p < 0.05). Multivariate Cox analysis showed that TCNP was an independent prognostic factor for breast cancer. Subgroup analysis indicated that for breast molecular subtypes and TNM stage II-III breast cancer, TCNP were related to worse prognosis. Multivariate logistic regression revealed that TCNP was an independent contributing factor for LN metastasis. Conclusion: In Chinese breast cancer, compared to TBPQ, TCNP is associated with more LN metastasis and poorer prognosis.

Analysis the effect of miR-141-3p/HMGB1 in LPS-induced mucus production and the apoptosis in nasal epithelial cells.

Allergic rhinitis (AR) is an allergic disease characterized by immunoglobulin E (IgE)-mediated type I hypersensitivity disorder. In the current study, we illuminated the potential roles of microRNA-141-3p (miR-141-3p) in lipopolysaccharide (LPS)-induced mucus production and the apoptosis in nasal epithelial cells (NECs). We demonstrated that miR-141-3p was significantly downregulated in nasal tissues from patients with AR and LPS-treated NECs. Upregulation of miR-141-3p decreased the level of mucin 5AC (MUC5AC) in LPS-treated NECs and induced NECs apoptosis. High Mobility Group Box 1 (HMGB1) was proved as a target of miR-141-3p and miR-141-3p negatively regulated its expression. In addition, we observed that HMGB1 was overexpressed in nasal mucosal tissues from patients with AR and LPS-treated NECs. Finally, we proved that miR-141-3p decreased the level of MUAC5AC in LPS-treated NECs through regulating HMGB1. In conclusion, miR-141-3p inhibited LPS-induced MUAC5AC production and the apoptosis of LPS-treated NECs by targeting HMGB1.

Identification of molecular mechanism underlying therapeutic effect of tanshinone IIA in the treatment of hypoxic vestibular vertigo via the NO/cGMP/BKCa signaling pathway.

This study aimed to investigate the molecular mechanisms underlying the effect of Tashinone IIA (Tan) on the treatment of ischemic vertigo. Sprague-Dawley (SD) male rats were divided into a SHAM group, a MODEL group, a MODEL+PBS group, a MODEL+Tan (10 mg/kg) group, a MODEL+Tan (20 mg/kg) group, a MODEL+Tan (40 mg/kg) group and a MODEL+Tan (80 mg/kg) group. The escape latency was observed among different groups of rats, while the production of NO/cGMP and the expression of BKCa were measured in vivo and in vitro by H&E staining, Western Blot and IHC assays. While the rats with ischemic vertigo showed prolonged escape latency, the treatment by Tan (40 mg/kg and up) shortened the escape latency in rats with ischemic vertigo. Moreover, the reduced production of NO/cGMP and expression of BKCa protein in the MODEL group were increased by a certain extent upon the treatment of 40 mg/kg or 80 mg/kg Tan. H&E staining of MVN neuron cells collected from different rat groups also validated the positive effects of Tan on the repair of damaged MVN neuron cells. Moreover, the above results were also validated in vitro, as the cells treated with 5 ug/ml and 10 ug/ml Tan increased the levels of NO/cGMP production and BKCa protein expression. At a certain dose, Tan could increase the production of NO and cGMP as well as the expression of BKCa, which would subsequently aid the treatment of ischemic vertigo.