Predictive value of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) for the short-term mortality of older patients with isolated traumatic brain injury: a retrospective cohort study.

OBJECTIVES: This study aimed to evaluate the effectiveness of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) in predicting 24-hour in-hospital mortality among patients aged 65 years and older with isolated traumatic brain injury (TBI). DESIGN: A retrospective, single-centre cohort study. SETTING: This study was conducted at a government-run tertiary comprehensive hospital. PARTICIPANTS: This study included 982 patients aged 65 years or older with isolated TBI, who were admitted to the emergency department between 1 January 2020 and 31 December 2021. INTERVENTIONS: None. PRIMARY OUTCOME: 24-hour in-hospital mortality was the primary outcome. RESULTS: Among the 982 patients, 8.75% died within 24 hours of admission. The non-survivors typically had higher TRIAGES and lower GCS scores. Logistic regression showed significant associations of both TRIAGES and GCS with mortality; the adjusted ORs were 1.98 (95% CI 1.74 to 2.25) for TRIAGES and 0.72 (95% CI 0.68 to 0.77) for GCS. Receiver operating characteristic (ROC) analysis indicated an area under the ROC curve of 0.86 for GCS and 0.88 for TRIAGES, with a significant difference (p=0.012). However, precision-recall curve (PRC) analysis revealed an area under the PRC of 0.38 for GCS and 0.47 for TRIAGES, without a significant difference (p=0.107). CONCLUSIONS: The TRIAGES system is a promising tool for predicting 24-hour in-hospital mortality in older patients with TBI, demonstrating comparable or slightly superior efficacy to the GCS. Further multicentre studies are recommended for validation.

Predictive value of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) and Revised Trauma Score (RTS) for the short-term mortality of patients with isolated traumatic brain injury.

BACKGROUND: Ensuring rapid and precise mortality prediction in patients with traumatic brain injury (TBI) at the emergency department (ED) is paramount in patient triage and enhancing their outcomes. We aimed to estimate and compare the predictive power of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate, and Systolic blood pressure score (TRIAGES) and Revised Trauma Score (RTS) for 24-h in-hospital mortality in patients with isolated TBI. METHODS: We conducted a retrospective single-center study analyzing clinical data from 1156 patients with isolated acute TBI treated in the ED of the Affiliated Hospital of Nantong University from January 1, 2020, to December 31, 2020. We calculated each patient's TRIAGES and RTS scores and estimated their predictive value for short-term mortality using receiver operating characteristic (ROC) curves. RESULTS: 87 patients (7.53%) died within 24 h of admission. The non-survival group had higher TRIAGES and lower RTS than the survival group. Compared to non-survivors, survivors exhibited higher Glasgow Coma Scale scores (GCS) with a median score of 15 (12, 15) compared to a median score of 4.0 (3.0, 6.0). The crude and adjusted odds ratios (ORs) for TRIAGES were 1.79, 95% CI (1.62 to 1.98) and 1.79, 95% CI (1.60 to 2.00), respectively. The crude and adjusted ORs for RTS were 0.39, 95% CI (0.33 to 0.45) and 0.40, 95% CI (0.34 to 0.47), respectively. The area under the ROC (AUROC) curve of TRIAGES, RTS, and GCS was 0.865 (0.844 to 0.884), 0.863 (0.842 to 0.882), and 0.869 (0.830 to 0.909), respectively. The optimal cut-off values for predicting 24-h in-hospital mortality were 3 for TRIAGES, 6.08 for RTS, and 8 for GCS. The subgroup analysis showed a higher AUROC in TRIAGES (0.845) compared to GCS (0.836) and RTS (0.829) among patients aged 65 and above, although the difference was not statistically significant. CONCLUSIONS: TRIAGES and RTS have shown promising efficacy in predicting 24-h in-hospital mortality in patients with isolated TBI, with comparable performance to GCS. However, improving the comprehensiveness of assessment does not necessarily translate into an overall increase in predictive ability.

[Retracted] CtBP1 interacts with SOX2 to promote the growth, migration and invasion of lung adenocarcinoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that, for the western blots showing the CtBP1 and SOX2 bands in Fig. 5C on p. 74, the data were in fact the same, but flipped horizontally; moreover, two pairs of overlapping data panels were identified comparing between the cell invasion and assay data images shown in Figs. 3E and 6C, such that these were likely to have been derived from the same original sources even though they were intended to show the results from differently performed experiments; similarly, the 'shSOX2 / 24 h' and 'shCtBP1 / 24  h' data panels in Fig. 6B showing the results of differently performed scratch­wound assay experiments appeared to be overlapping, albeit with one of the panels being slightly rotated relative to the other. Finally, there were erroneous calculations included for the CtBP1 expression data shown in Table III.  Given the large number of apparent errors that were made during the assembly of various of the figures and Table III in this paper, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal due to an overall lack of confidence in the presented data. After contacting the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 67­78, 2019; DOI: 10.3892/or.2019.7142].

Association between admission systemic immune-inflammation index and mortality in critically ill patients with sepsis: a retrospective cohort study based on MIMIC-IV database.

Systemic immune-inflammation index (SII) has been identified as a prognostic biomarker for various diseases. Our study aimed to investigate the association between SII and mortality risk in critically ill patients with sepsis, thus exploring possible tools for rapid screening. This retrospective cohort study was conducted using clinical data extracted from the Medical Information Mart for Intensive Care Database. The study included only patients diagnosed with sepsis admitted to the intensive care unit for the first time. We used the restricted cubic splines to explore the relationship between SII and 28-day mortality. Kaplan-Meier curve and Cox regression models were performed to evaluate the association between SII and mortality. Subgroup analysis was performed to explore the stability of the primary results. A total of 16,007 patients with sepsis were eligible in the final analysis. We found a J-shaped relationship between SII and mortality risk. The SII level associated with the lowest mortality risk was 774.46*109/L. Compared with the reference group (second SII quartile), the 28-day mortality was increased in the highest quartile and third quartile groups of SII levels; fully adjusted HRs were 1.16 (1.02 to 1.32) and 1.40 (1.23 to 1.58), respectively. However, although the lower SII (Q1 group) also showed a trend toward a higher hazard of 28-day mortality, there was no statistical difference, with a fully adjusted HR of 1.05 (0.92 to 1.21). In the population of critically ill patients with sepsis, low and high SII levels were associated with an increased risk of short-term mortality. The 28-day mortality risk was lowest at SII levels of 774.46*109/L.

Blocking vicious cycle of cardiac dysfunction by external cardiopulmonary resuscitation is the key to rescue acute aluminium phosphide poisoning.

Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction.

Prognostic biomarker TUBA1C is correlated to immune cell infiltration in the tumor microenvironment of lung adenocarcinoma.

BACKGROUND: TUBA1C is a microtubule component that is involved in a variety of cancers. Our main objective was to investigate TUBA1C expression, its prognostic value, its potential biological functions, and its impact on the immune system of patients with lung adenocarcinoma (LUAD). METHODS: The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Immunohistochemistry Analysis were used to analyze TUBA1C expression, its clinicopathology, overall survival (OS), and disease-free survival (DFS) in LUAD patients. We also determined the correlation between TUBA1C and tumor-infiltrating immune cells (TIICs) by using CIBERSORT and GEPIA databases. To determine the expression of TUBA1C in LUAD, we analyzed a collection of immune infiltration levels and cumulative survival of LUAD tissues in TIMER database. By using UALCAN, STRING, and GeneMANIA databases, we investigated the protein-coding genes related to TUBA1C and its co-expression genes in LUAD tissues. Gene set enrichment analysis (GSEA) was performed by using the TCGA dataset. RESULTS: The mRNA and the protein expression of TUBA1C were found to be up-regulated in LUAD tissues. The univariate analysis indicated that an increased expression of TUBA1C was significantly correlated to the following parameters: age, stage, and lymph node metastasis. An over-expression of TUBA1C was associated with a poor prognosis of LUAD. In TIMER and CIBERSORT databases, we found that TUBA1C is correlated with 13 types of TIICs: activated B cell, activated CD4 T cell, central memory CD4 T cell, effector memory CD8 T cell, eosinophils, immature B cell, gamma-delta T cell, immature dendritic cell, mast cell, memory B cell, natural killer T cell, regulatory T cell, and type 2T helper cell. By performing GSEA, we found that TUBA1C is closely correlated to cell cycle, p53 signaling pathway, glycolysis, and gluconeogenesis. CONCLUSIONS: Our findings indicate that TUBA1C is associated with TIICs in tumor microenvironment. Therefore, it serves as a novel prognostic biomarker and a target for future treatment methods of LUAD.

Serum heart-type fatty acid-binding protein as a predictor for the development of sepsis-associated acute kidney injury.

Background: We analyzed the correlation between heart-type fatty acid-binding protein (HFABP) and the development of acute kidney injury (AKI) in patients with sepsis and estimated the predictive capacity of HFABP for sepsis-associated acute kidney injury (SAKI). Methods: In this retrospective observational study, we screened 2,452 patients who received the HFABP test in the emergency department. 442 admitted patients with sepsis were finally enrolled. Based on the diagnostic criteria for AKI in Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, patients were divided into the no-AKI group (n = 317) and AKI group (n = 125). We analyzed the correlation between HFABP and SAKI occurrence by logistic regression analysis and evaluated the predictive ability of HFABP to SAKI using c-index, net reclassification improvement index (NRI) and integrated discrimination improvement index (IDI). Results: Patients in the AKI group with significantly higher the level of HFABP and in-hospital mortality. HFABP concentration is an independent risk factor for SAKI (OR: 11.398; 95% CI: 6.218-20.891, P < 0.001), but not for in-hospital mortality (OR: 1.189, 95%CI: 0.954-2.607, P = 0.076). The addition of HFABP to the prediction model significantly improved the ROC area (0.867 vs 0.755, P < 0.001), NRI 25.03% (95% CI 9.72-38.51%) and IDI 14.33 (95% CI 11.04-17.62). Conclusion: Serum HFABP is correlated with SAKI development and could become a potential predictive biomarker.

CtBP1 interacts with SOX2 to promote the growth, migration and invasion of lung adenocarcinoma.

Carboxyl­terminal binding protein 1 (CtBP1) is overexpressed in many types of solid tumors and has been found to be functionally associated with proliferation, migration, invasion and drug resistance of cancer cells. However, its expression pattern and functions in lung adenocarcinoma remain unclear. In the present study, we observed that the expression of CtBP1 was upregulated in the lung adenocarcinoma tissues of patients with lymph node metastasis and that its overexpression was correlated with tumor differentiation, size and poor overall survival. Silencing of CtBP1 by transfection with shRNA inhibited the proliferation, migration and invasion of A459 lung adenocarcinoma cells in vitro as determined by MTT assay and Transwell assay, respectively. In vivo studies using a lung patient­derived tumor xenograft (PDTX) mouse model implicated CtBP1 expression in lung adenocarcinoma growth, and further in vitro co­immunoprecipitation and depletion experiments indicated that CtBP1 regulated the biological behavior of lung adenocarcinoma cells by interacting with SOX2. Patients with elevated expression of both CtBP1 and SOX2 expression had a significantly shorter overall survival rate than patients with reduced expression of these transcripts, or than patients with elevated expression of only one transcript (P<0.01 in both cases). Taken together, these findings suggest that CtBP1 plays an important role in lung adenocarcinoma and, along with SOX2, may serve as a viable prognostic marker and therapeutic target for lung adenocarcinoma.

Overexpression of fibronectin type III domain containing 3B is correlated with epithelial-mesenchymal transition and predicts poor prognosis in lung adenocarcinoma.

Fibronectin (FN) type III domain containing 3B (FNDC3B), a member of the FN family, regulates the invasion and metastasis of cells in numerous tumor types. However, the mechanisms through which FNDC3B regulates carcinogenesis in lung adenocarcinoma (LADC) tissues have remained elusive. The present study revealed that the protein levels of FNDC3B and vimentin were significantly elevated in LADC tissues compared with those in normal lung tissues. By contrast, the expression of E-cadherin was decreased in LADC tissues compared with that in normal lung tissues. Furthermore, the aberrant expression of FNDC3B and epithelial-mesenchymal transition (EMT) markers was significantly associated with histological differentiation, lymph node metastasis and tumor-nodes-metastasis stage. Kaplan-Meier analysis indicated that a high expression of FNDC3B may be associated with poor overall survival of patients with LADC. In addition, overexpression of FNDC3B promoted the protein expression of EMT-associated genes in the A549 lung adenocarcinoma cell line. In conclusion, the present results support the notion that FNDC3B acts as an oncogene in LADC; it may serve a pivotal role in the development and progression of LADC and may participate in the regulation of the EMT.

Lepidic component at tumor margin: an independent prognostic factor in invasive lung adenocarcinoma.

Previous studies have proven that the lepidic component of lung adenocarcinoma is an independent prognostic factor and has a favorable effect on patient prognosis; however, no studies have reported the specific distribution of the lepidic component in lung cancer. In this study, we focused mainly on whether the lepidic component at the tumor margin was an independent prognostic factor for invasive lung adenocarcinoma. We reviewed 276 patients with invasive lung adenocarcinomas and divided them into 2 groups-181 with tumors of 3 cm or less and 95 with tumors of greater than 3 cm-to study their histopathologic and clinicopathological characteristics. The long lepidic structure at the tumor margin was designated as the marginal lepidic feature. In the group with tumors of 3 cm or less, the lepidic component and marginal lepidic feature were significantly associated with histologic subtype, TNM stage, and lymph node metastasis (P < .05), whereas in the group with tumors of greater than 3 cm, the lepidic component and marginal lepidic feature were not correlated with histopathologic or clinicopathological characteristics. Furthermore, the patients with tumors of 3 cm or less and marginal lepidic lesions demonstrated significantly longer overall survival than did those without the structure (P < .001). We concluded that the marginal lepidic feature of invasive lung adenocarcinoma is a significant histologic feature that suggests a better prognosis.

miR-335 inhibited cell proliferation of lung cancer cells by target Tra2ß.

Accumulating evidence has suggested that the dysregulation of miRNA is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, while the expression of Tra2ß is increased. In addition, clinical data revealed that the increased Tra2ß and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. In vitro experimentation showed that the overexpression of miR-335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2ß. In contrast, inhibition of miR-335 or overexpression of the Tra2ß target gene stimulated the growth, invasion and migratory capabilities of A459 lung cancer cells in vitro. Furthermore, overexpression of miR-335 or inhibition of Tra2ß decreased the phosphorylation of Rb-S780 and Rb-AKT. Overall, these findings suggest that the downregulation of miR-335 in A459 lung cancer cells promoted cell proliferation through upregulation of Tra2ß, mediated via activation of the AKT/mTOR signaling pathway, and suggest that miR-335 may have potential as a novel therapeutic target for NSCLC.

Combination of cadherin-17 and SATB homeobox 2 serves as potential optimal makers for the differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma.

BACKGROUND: Pulmonary enteric adenocarcinoma (PEAC), a rare type of non-small cell lung cancer, has similar histological and immunohistochemical morphology to colorectal adenocarcinoma. Cadherin-17 (CDH17) and SATB homeobox 2 (SATB2) immunoexpression have recently been demonstrated in colorectal adenocarcinoma. In this study, we evaluated the value of CDH17 and SATB2 in the diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal adenocarcinoma. METHODS: A total of 13 PEAC cases and 27 metastatic colorectal adenocarcinoma cases were enrolled in our cohort study. We analyzed the expressions of CK7, CK20, CDX-2, villin, cadherin-17 (CDH17), and SATB homeobox 2 (SATB2) using immunohistochemistry. Staining intensity and percentage of positive-staining cells were recorded. Sensitivity and specificity values for immunostains, individually and in combination, were computed and compared. RESULTS: Combining CDH17 and SATB2 resulted in high sensitivity (76.92%) and specificity (100%). In our study, the use of CK7+, napsin A+, TTF-1+, napsin A+TTF-1+ in combination with CDH17-/SATB2- had a higher area under the curve compared to the combination CDH17-/SATB2-. However, no significant differences were observed between the combination CDH17-/SATB2- and other combinations (P>0.05). CONCLUSIONS: In combination, CDH17 and SATB2 serve as potential optimal markers for the differential diagnosis of PEAC and metastatic colorectal adenocarcinoma.

miR-1236-3p suppresses the migration and invasion by targeting KLF8 in lung adenocarcinoma A549 cells.

MicroRNAs (miRNAs) have a great effect on regulating tumor cell migration, invasion, proliferation and prognosis. However, the mechanism of miR-1236-3p on regulating carcinogenesis is still unknown. In this study, the expression of miR-1236-3p was lower in lung adenocarcinoma tissues than that in adjacent normal tissue. In lung adenocarcinoma A549 cell line, miR-1236-3p decreased ability of cell invasion and migration, furthermore, we show that KLF8 is targeted by miR-1236-3p, and expression of miR-1236-3p is negatively correlated with KLF8. Additionally, miR-1236-3p suppressed the expression of KLF8 and EMT (epithelial mesenchymal transition)-related genes. Overexpression of KLF8 can promote EMT-related genes at protein level. In conclusion, our results support the fact that miR-1236-3p acts as a tumor inhibitor in lung adenocarcinoma by suppressing the activity of KLF8, and it may play a critical role in the diagnosis and treatment of lung cancer.

Role of the ER stress in prostaglandin E2/E-prostanoid 2 receptor involved TGF-ß1-induced mice mesangial cell injury.

This study aims to investigate the relationship between prostaglandin E2 E-prostanoid 2 receptor (EP2) and Endoplasmic reticulum (ER) stress in transforming growth factor-ß1 (TGF-ß1)-induced mouse glomerular mesangial cells (MCs) injury. We cultured primary WT, EP2(-/-) MCs (EP2 deleted), and adenovirus-EP2-infected WT MCs (EP2 overexpressed). PCR, Western blot, flow cytometry, and immunohistochemical technique were used in in vitro and in vivo experiments. We found that TGF-ß1-induced PGE2 synthesis decreased in EP2-deleted MCs and increased in EP2-overexpressed MCs. EP2 deficiency in these MCs augmented the coupling of TGF-ß1 to ER stress-associated proteins [chaperone glucose-regulated protein 78 (GRP78), transient receptor potential channel 1 (TRPC1), and transient receptor potential channel 4 (TRPC4)], and upregulation of EP2 showed no significant change of GRP78, but augmented the expression of TRPC1, while TRPC4 expression was downregulated in comparison to normal MCs. In addition, EP2 deficiency in MCs augmented TGF-ß1-induced fibronectin (FN), cyclooxygenase-2 (COX2), and CyclinD1 expression. Silencing of EP2 also strengthened TGF-ß1-induced extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Flow Cytometry showed that silencing of EP2 significantly promoted the apoptosis of MCs. In contrast, EP2 overexpression reversed the effects of EP2 deficiency. 8 weeks after 5/6 nephrectomy (Nx), blood urea nitrogen and creatinine concentrations were significantly increased in EP2(-/-) 5/6Nx mice as compared to those of WT 5/6Nx mice. The pathological changes in kidney of EP2(-/-) mice were markedly aggravated compared with WT mice. Immunohistochemical analysis showed significant augment of TRPC4 and ORP150 in the kidney of EP2(-/-) mice compared with WT mice. Considering all the findings, it is suggested that increased expression of EP2 may prevent TGF-ß1-induced MCs damage through ER stress regulatory pathway.

Prostaglandin E2 EP1 receptor enhances TGF-ß1-induced mesangial cell injury.

Increasing evidence indicates that transforming growth factor-ß1 (TGF-ß1) is a pivotal mediator in the pathogenesis of renal fibrosis. Mesangial cells (MCs) are important for glomerular function under both physiological and pathological conditions. Studies have found that the expression level of prostaglandin E2 (PGE2) in MCs increases under high glucose conditions, that PGE2 affects the proliferation and hypertrophy of MCs mainly through the EP1 pathway, and that the proliferation of MCs and the accumulation of extracellular matrix are the main events leading to glomerular fibrosis. In this study, we investigated the effects and mechanisms of action of the EP1 receptor, which is induced by transforming growth factor (TGF)-ß1, on the proliferation of mouse MCs, the accumulation of extracellular matrix and the expression of PGE2 synthase. Primary mouse glomerular MCs were isolated from EP1 receptor-deficient mice (EP1-/- mice, in which the EP1 receptor was knocked down) and wild-type (WT) mice (WT MCs). In our preliminary experiments, we found that cell proliferation, as well as the mRNA and protein expression of cyclin D1, proliferating cell nuclear antigen (PCNA), fibronectin (FN), collagen I (ColI), membrane-associated PGE2 synthase-1 (mPGES-1) and cyclooxygenase-2 (COX-2) in the WT MCs were significantly increased following treatment with 10 ng/ml TGF-ß1 for 24 h. Compared with the WT MCs, following the knockdown of the EP1 gene, the TGF-ß1-induced MC injury was markedly suppressed. The aforementioned changes were notably enhanced following treatment with the EP1 agonist, 17-phenyl trinor PGE2 ethyl amide. Additionally, TGF-ß1 induced extracellular signal-regulated kinase (ERK) phosphorylation. We found that the TGF-ß1-induced ERK phosphorylation was alleviated by EP1 knockdown and promoted by EP1 expression. These results suggest that the EP1 receptor plays a role in the proliferation of mouse MCs, in the accumulation of extracellular matrix and in the expression of mPGES-1 induced by TGF-ß1. Its mechanisms of action are possibly related to the reinforcement of ERK phosphorylation.