A risk prediction model for efficient intubation in the emergency department: A 4-year single-center retrospective analysis.

Objective: To analyze the risk factors associated with intubated critically ill patients in the emergency department (ED) and develop a prediction model by machine learning algorithms. Methods: This study was conducted in an academic tertiary hospital in Hangzhou, China. Critically ill patients admitted to the ED were retrospectively analyzed from May 2018 to July 2022. The demographic characteristics, distribution of organ dysfunction, parameters for different organs' examination, and status of mechanical ventilation were recorded. These patients were assigned to the intubation and non-intubation groups according to ventilation support. We used the eXtreme Gradient Boosting (XGBoost) algorithm to develop the prediction model and compared it with other algorithms, such as logistic regression, artificial neural network, and random forest. SHapley Additive exPlanations was used to analyze the risk factors of intubated critically ill patients in the ED. Results: Of 14,589 critically ill patients, 10,212 comprised the training group and 4377 comprised the test group; 2289 intubated patients were obtained from the electronic medical records. The mean age, mean scores of vital signs, parameters of different organs, and blood oxygen examination results differed significantly between the two groups (p < 0.05). The white blood cell count, international normalized ratio, respiratory rate, and pH are the top four risk factors for intubation in critically ill patients. Based on the risk factors in different predictive models, the XGBoost model showed the highest area under the receiver operating characteristic curve (0.84) for predicting ED intubation. Conclusions: For critically ill patients in the ED, the proposed model can predict potential intubation based on the risk factors in the clinically predictive model.

S100A11: A Potential Carcinogen and Prognostic Marker That Correlates with the Immunosuppressive Microenvironment in Pan-Cancer.

S100 calcium-binding protein A11 (S100A11) has been proved to be an oncogene of most tumors. However, its role in the tumor microenvironment (TME) in pan-cancer stills remains poorly understood. This study used public data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to evaluate the expression of S100A11. The R package "GSVA" was used for Gene set variation analysis (GSVA) of S100A11. The R package "ESTIMATE" was used to further explore the relationship between S100A11 and TME. The Genomics of Drug Sensitivity in Cancer database was used to investigate the effect of S100A11 on the efficiency of anticancer drugs. We found S100A11 expression was upregulated in most tumors and predicted a poor prognosis. Furthermore, S100A11 expression was closely associated with immune regulation-related pathways. Moreover, S100A11 expression in pan-cancer was significantly related to most immunosuppressive cells, such as tumor-associated macrophages (TAM), tumor-associated fibroblasts (TAF), and Treg cells. The expression of S100A11 was significantly related to immunosuppressive genes and immune checkpoints in most tumor types. Additionally, the upregulation of S100A11 expression made patients with cancer resistant to the treatment of most anticancer drugs, such as sorafenib. In brief, our study showed that S100A11 could be used as a potential carcinogen and prognostic marker for most tumor types. The increased expression of S100A11 was closely related to tumor immunosuppressive TME. The upregulation of S100A11 expression made patients with cancer resistant to sorafenib treatment.

A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment.

The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance, rendering them with limited therapies. To discover new regimens for the treatment of PCa including resistant PCa, natural products, the richest source of bioactive compounds, can serve as a library for screening and identifying promising candidates, and flavones such as apigenin and genistein have been used in lab and clinical trials for treating PCa over decades. In this mini-review, we take a look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade. While possessing very similar structure, these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells. Given that more combinations are being developed and tested, genistein appears to be the more promising option to be approved. The anticancer efficacies of these two flavones can be confirmed by in-vitro and in-vivo studies, and their applications remain to be validated in clinical trials. Information gained in this work may provide important information for new drug development and the potential application of apigenin and genistein in treating PCa.

Construction and Screening of Fractional Library of Salviae Miltiorrhizae Radix et Rhizoma for the Rapid Identification of Active Compounds against Prostate Cancer.

Efficient screening of anticancer agents is in urgent need to develop new drugs that combat malignant tumors and drug resistance. In this study, a combined strategy composed by solvent partition and HPLC fractionation was developed to generate an herbal fraction library of Salviae Miltiorrhizae Radix et Rhizoma to quickly and efficiently screen anticancer agents. All library entries are directed into 96 well plates which are well mapped with HPLC chromatograms. The cell proliferation assay revealed seven active subfractions. Then, the major active ten peaks in these subfractions were prepared and isolated by semipreparative HPLC, and their inhibitory activities against prostate cancer cells were then tested at the same concentration level, leading to the identification of several active compounds. In addition, the structures of compounds arucadiol (2), 15,16-dihydrotanshinone I (4), methyl tanshinonate (5), cryptanshinone (7), 1,2-dihydrotanshinquinone I (9), and tanshinone IIA (10) were characterized by mass spectrometry and X-ray crystallographic analysis, and they were confirmed to be active in suppressing prostate cancer cell proliferation at 7.5 or 15 µg/mL, among which, the minor compounds 2, 4, and 5 showed higher activities than 9 and 10. This study provided a rapid strategy of identifying new anticancer agents in Salviae Miltiorrhizae Radix et Rhizoma, which can be applied in other herbal medicines.

Efficacy of caspofungin combined with trimethoprim/sulfamethoxazole as first-line therapy to treat non-HIV patients with severe pneumocystis pneumonia.

Combined treatment with caspofungin and trimethoprim/sulfamethoxazole (TMP/SMZ) as salvage therapy in non-HIV positive patients with severe pneumocystis pneumonia (PCP) yields poor outcomes. It remains unknown whether the use of this combination strategy as a first-line therapy would improve patient outcomes. The present study aimed to assess the efficacy of caspofungin combined with TMP/SMZ as a first-line therapy in non-HIV positive patients with severe PCP. A retrospective cohort study was conducted between March 2016 and February 2017. Patient clinical characteristics and outcomes were compared between two groups receiving first-line and second-line therapy respectively. In addition, similar cases from previous studies were assessed. A total of 14 patients were included in the present study (mean age, 58.79±14.41 years); including 9 patients receiving caspofungin and TMP/SMZ as a first-line therapy and 5 that received it as a second-line therapy. The overall positive response rate was 71.43% (10/14), with 88.89 (8/9) and 40.00% (2/5) in the first-line and second-line therapy groups, respectively (P=0.095). The positive response rates of patients requiring invasive mechanical ventilation differed significantly between the first-line (5/6, 83.33%) and the second-line (0/3, 0%) therapy groups (P=0.048). All-cause hospital mortality was 42.86% (6/14), with mortality rates of 33.33 (3/9) and 60.00% (3/5) in the first-line and second-line therapy groups, respectively (P=0.580). Combined with previously reported cases (n=27), the positive response rate was significantly greater in the first-line therapy group (11/12, 91.67%) than in the second-line therapy group (8/15, 53.33%, P=0.043). No significant differences were in all-cause mortality rates between the two groups (25.00 vs. 46.67%, P=0.424) were identified, despite the fact that all-course mortality in the first-line therapy group was ~50% that of the second-line therapy group. Therefore, the results of the present study indicate that combined caspofungin and TMP/SMZ as first-line therapy may be a promising and effective strategy to treat non-HIV positive patients with severe PCP, particularly for those requiring invasive mechanical ventilation.

Nestin overexpression promotes the embryonic development of heart and brain through the regulation of cell proliferation.

Nestin, an intermediate filament protein, is a key regulator of various extracellular proteins that play important roles in cell growth and differentiation. In recent years, nestin has been widely accepted as a molecular marker for neural stem/progenitor cells. However, its function during embryogenesis remains largely unknown since its depletion is lethal after stage embryonic day 8.5 (E8.5). In order to understand the role of this protein in vivo, we compared the heart and brain tissues of control mice with those of mice overexpressing a human nestin cDNA transgene under the control of a ROSA26 promoter. In these tissues we examined the general histology and cell size, the presence of apoptotic cells by TUNEL assay, and the presence of progenitor cell markers like SOX2. Compared to controls, mouse embryos overexpressing the human nestin transgene have a larger size and display characteristic morphological changes including a larger heart and forebrain. In these tissues we found corresponding increases in the size of cardiomyocytes and brain cells, as well as indications of augmented cell proliferation. In contrast, apoptosis was not significantly altered. Co-staining brain sections with SOX2 and Ki67 showed that most of the proliferating cells in the forebrain were neural stem cells. Moreover, nestin overexpression was responsible for a marked activation of the PI3K/Akt signaling pathway. Taken together, the results of this study indicate that nestin plays an important role in the embryonic development of at least two mouse organs (heart and brain) through the regulation of cell proliferation.

Correlation of overexpression of nestin with expression of epithelial-mesenchymal transition-related proteins in gastric adenocarcinoma.

BACKGROUND: Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. MATERIALS AND METHODS: The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. RESULTS: Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. CONCLUSIONS: Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy.