Machine Learning Predictive Model for Septic Shock in Acute Pancreatitis with Sepsis.

Objective: Acute pancreatitis (AP) progresses to septic shock can be fatal. Early identification of high-risk patients and timely intervention can prevent and interrupt septic shock. By analyzing the clinical characteristics of AP with sepsis, this study uses machine learning (ML) to build a model for early prediction of septic shock within 28 days of admission, which guided emergency physicians in resource allocation and medical decision-making. Methods: This retrospective cohort study collected data from the emergency departments (EDs) of three tertiary care hospitals in China. The dataset was randomly divided into a training dataset (70%) and a testing dataset (30%). Ten ML classifiers were utilized to analyze characteristics of AP with sepsis in the training dataset upon admission. Results were evaluated through cross-validation analysis. The optimal model was then tested on the testing dataset without any parameter modifications. The ML model was evaluated using the receiver operating characteristic curve (ROC) and compared to scoring systems through the DeLong test. Results: A total of 604 AP patients with sepsis were included in this study. The auto-encoder (AE) model based on mean normalization, Pearson correlation coefficient (PCC), and recursive feature elimination (RFE) selection, achieved the highest Area Under the Curve (AUC) on the validation dataset (AUC 0.900, accuracy 0.868), with the AUC of 0.879 and accuracy of 0.790 on the testing dataset. Compared to the Sequential Organ Failure Assessment (AUC 0.741), quick Sequential Organ Failure Assessment (AUC 0.727), Acute Physiology and Chronic Health Evaluation II (AUC 0.778), and Bedside Index of Severity in Acute Pancreatitis (AUC 0.691), the AE model showed superior performance. Conclusion: The AE model outperforms traditional scoring systems in predicting septic shock in AP patients with sepsis within 28 days of admission. This assists emergency physicians in identifying high-risk patients early and making timely medical decisions.

Senescence-related genes analysis in breast cancer reveals the immune microenvironment and implications for immunotherapy.

Despite the advent of precision therapy for breast cancer (BRCA) treatment, some individuals are still unable to benefit from it and have poor survival prospects as a result of the disease's high heterogeneity. Cell senescence plays a crucial role in the tumorigenesis, progression, and immune regulation of cancer and has a major impact on the tumor microenvironment. To find new treatment strategies, we aimed to investigate the potential significance of cell senescence in BRCA prognosis and immunotherapy. We created a 9-gene senescence-related signature. We evaluated the predictive power and the role of signatures in the immune microenvironment and infiltration. In vitro tests were used to validate the expression and function of the distinctive critical gene ACTC1. Our risk signature allows BRCA patients to receive a Predictive Risk Signature (PRS), which may be used to further categorize a patient's response to immunotherapy. Compared to conventional clinicopathological characteristics, PRS showed strong predictive efficacy and precise survival prediction. Moreover, PRS subgroups were examined for altered pathways, mutational patterns, and possibly useful medicines. Our research offers suggestions for incorporating senescence-based molecular classification into risk assessment and ICI therapy decision-making.

Development and Validation of a Rapid and Efficient Prognostic Scoring System for Sepsis Based on Oxygenation Index, Lactate and Glasgow Coma Scale.

Objective: To develop a concise scoring system for efficient and rapid assessment of sepsis prognosis applicable to emergency departments. Methods: This was a single-center retrospective cohort study of patients with sepsis. In this study, a new scoring system (oxygenation index, lactate, and Glasgow coma scale: GOL) was developed through a derivation group, and then the GOL was validated using a validation group. Multivariate logistic regression analysis was performed to investigate the relationship between GOL and 28-day adverse outcomes. The GOL was compared with the previous scoring system using receiver operating characteristic curves (ROC) and decision analysis curves. The endpoints of this study were mortality, mechanical ventilation (MV), and admission to the intensive care unit (AICU). Results: 608 patients were included in the derivation group and 213 patients in the validation group, with 131 and 42 deaths, respectively. In the validation group, lactate (Lac), oxygenation index (PaO2/FiO2), and Glasgow coma scale score (GCS), the three best performers in predicting 28-day mortality from receiver operating characteristic curves, were used to construct the GOL. The higher the GOL score, the higher the incidence of death, MV and AICU within 28 days. Multifactorial logistic regression analysis showed that when the GOL was greater than 1, it was an independent risk factor for 28-day mortality, MV, and AICU. In predicting 28-day mortality, GOL was superior to the quick Sequential Organ Failure Assessment (qSOFA), Mortality in Emergency Department Sepsis Score (MEDS), Systemic Inflammatory Response Syndrome Score (SIRS), and Modified Early Warning Score (MEWS), and was comparable to the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA). Conclusion: The GOL is a simple, rapid, and accurate method for early identification of patients at increased risk of in-hospital death from sepsis.

Exploring the role of sphingolipid-related genes in clinical outcomes of breast cancer.

Background: Despite tremendous advances in cancer research, breast cancer (BC) remains a major health concern and is the most common cancer affecting women worldwide. Breast cancer is a highly heterogeneous cancer with potentially aggressive and complex biology, and precision treatment for specific subtypes may improve survival in breast cancer patients. Sphingolipids are important components of lipids that play a key role in the growth and death of tumor cells and are increasingly the subject of new anti-cancer therapies. Key enzymes and intermediates of sphingolipid metabolism (SM) play an important role in regulating tumor cells and further influencing clinical prognosis. Methods: We downloaded BC data from the TCGA database and GEO database, on which we performed in depth single-cell sequencing analysis (scRNA-seq), weighted co-expression network analysis, and transcriptome differential expression analysis. Then seven sphingolipid-related genes (SRGs) were identified using Cox regression, least absolute shrinkage, and selection operator (Lasso) regression analysis to construct a prognostic model for BC patients. Finally, the expression and function of the key gene PGK1 in the model were verified by in vitro experiments. Results: This prognostic model allows for the classification of BC patients into high-risk and low-risk groups, with a statistically significant difference in survival time between the two groups. The model is also able to show high prediction accuracy in both internal and external validation sets. After further analysis of the immune microenvironment and immunotherapy, it was found that this risk grouping could be used as a guide for the immunotherapy of BC. The proliferation, migration, and invasive ability of MDA-MB-231 and MCF-7 cell lines were dramatically reduced after knocking down the key gene PGK1 in the model through cellular experiments. Conclusion: This study suggests that prognostic features based on genes related to SM are associated with clinical outcomes, tumor progression, and immune alterations in BC patients. Our findings may provide insights for the development of new strategies for early intervention and prognostic prediction in BC.

Integrating single-cell RNA-seq and bulk RNA-seq to construct prognostic signatures to explore the role of glutamine metabolism in breast cancer.

Background: Although breast cancer (BC) treatment has entered the era of precision therapy, the prognosis is good in the case of comprehensive multimodal treatment such as neoadjuvant, endocrine, and targeted therapy. However, due to its high heterogeneity, some patients still cannot benefit from conventional treatment and have poor survival prognoses. Amino acids and their metabolites affect tumor development, alter the tumor microenvironment, play an increasingly obvious role in immune response and regulation of immune cell function, and are involved in acquired and innate immune regulation; therefore, amino acid metabolism is receiving increasing attention. Methods: Based on public datasets, we carried out a comprehensive transcriptome and single-cell sequencing investigation. Then we used 2.5 Weighted Co-Expression Network Analysis (WGCNA) and Cox to evaluate glutamine metabolism-related genes (GRGs) in BC and constructed a prognostic model for BC patients. Finally, the expression and function of the signature key gene SNX3 were examined by in vitro experiments. Results: In this study, we constituted a risk signature to predict overall survival (OS) in BC patients by glutamine-related genes. According to our risk signature, BC patients can obtain a Prognostic Risk Signature (PRS), and the response to immunotherapy can be further stratified according to PRS. Compared with traditional clinicopathological features, PRS demonstrated robust prognostic power and accurate survival prediction. In addition, altered pathways and mutational patterns were analyzed in PRS subgroups. Our study sheds some light on the immune status of BC. In in vitro experiments, the knockdown of SNX3, an essential gene in the signature, resulted in a dramatic reduction in proliferation, invasion, and migration of MDA-MB-231 and MCF-7 cell lines. Conclusion: We established a brand-new PRS consisting of genes associated with glutamine metabolism. It expands unique ideas for the diagnosis, treatment, and prognosis of BC.

Optimal Selection of Imaging Examination for Lymph Node Detection of Breast Cancer With Different Molecular Subtypes.

Objective: Axillary lymph node management is an important part of breast cancer surgery and the accuracy of preoperative imaging evaluation can provide adequate information to guide operation. Different molecular subtypes of breast cancer have distinct imaging characteristics. This article was aimed to evaluate the predictive ability of imaging methods in accessing the status of axillary lymph node in different molecular subtypes. Methods: A total of 2,340 patients diagnosed with primary invasive breast cancer after breast surgery from 2013 to 2018 in Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University were included in the study. We collected lymph node assessment results from mammography, ultrasounds, and MRIs, performed receiver operating characteristic (ROC) analysis, and calculated the sensitivity and specificity of each test. The C-statistic among different imaging models were compared in different molecular subtypes to access the predictive abilities of these imaging models in evaluating the lymph node metastasis. Results: In Her-2 + patients, the C-statistic of ultrasound was better than that of MRI (0.6883 vs. 0.5935, p=0.0003). The combination of ultrasound and MRI did not raise the predictability compared to ultrasound alone (p=0.492). In ER/PR+HER2- patients, the C-statistic of ultrasound was similar with that of MRI (0.7489 vs. 0.7650, p=0.5619). Ultrasound+MRI raised the prediction accuracy compared to ultrasound alone (p=0.0001). In ER/PR-HER2- patients, the C-statistics of ultrasound was similar with MRI (0.7432 vs. 0.7194, p=0.5579). Combining ultrasound and MRI showed no improvement in the prediction accuracy compared to ultrasound alone (p=0.0532). Conclusion: From a clinical perspective, for Her-2+ patients, ultrasound was the most recommended examination to assess the status of axillary lymph node metastasis. For ER/PR+HER2- patients, we suggested that the lymph node should be evaluated by ultrasound plus MRI. For ER/PR-Her2- patients, ultrasound or MRI were both optional examinations in lymph node assessment. Furthermore, more new technologies should be explored, especially for Her2+ patients, to further raise the prediction accuracy of lymph node assessment.

Which Has a Greater Impact on the Recurrence in Young Breast Cancer Patients: Recent Childbirth or Recent Breastfeeding?

Purpose: This study explored the effects of recent childbirth and recent breastfeeding on the risk of recurrence in patients with postpartum breast cancer (PPBC). Materials and Methods: A bidirectional cohort study was conducted in the First Affiliated Hospital of Nanjing Medical University. 1013 young female breast cancer patients between May 2003 and October 2019 were enrolled. Breast cancer cases were grouped according to the time between giving birth or weaning and diagnosis. The end point of the analysis was disease-free survival (DFS). Results: Breast cancer patients diagnosed within 2 years after parturition showed more tumor characteristics that represented poor prognosis and remained at an increased risk for recurrence, even after adjusting for confounding factors (HR = 1.83, p=0.035). When the analysis was limited to patients with ER positive or histological grades I and II, they had a higher risk of recurrence. When weaning was used as the grouping node, patients diagnosed within 2 years after weaning did not show a higher risk of recurrence after adjustment, even when analysis was nearly limited to ER-positive patients. Conclusion: Recent reproductive history is an independent prognostic factor and seems to have a stronger impact on breast cancer with lower malignancy. In addition, the effect of recent childbirth on the recurrence of young breast cancer is significantly stronger than that of recent breastfeeding.

Comparative analysis of transient receptor potential channel 5 opposite strand-induced gene expression patterns and protein-protein interactions in triple-negative breast cancer.

In patients with triple-negative breast cancer (TNBC), high tumour mutation burden and aberrant oncogene expression profiles are some of the causes of poor prognosis. Therefore, it is necessary to identify aberrantly expressed oncogenes, since they have the potential to serve as therapeutic targets. Transient receptor potential channel 5 opposite strand (TRPC5OS) has been previously shown to function as a novel tumour inducer. However, the underlying mechanism of TRPC5OS function in TNBC remain to be elucidated. Therefore, in the present study TRPC5OS expression was first measured in tissue samples of patients with TNBC and a panel of breast cancer cell lines (ZR-75-1, MDA-MB-453, SK-BR-3, JIMT-1, BT474 and HCC1937) by using qRT-PCR and Western blotting. Subsequently, the possible effects of TRPC5OS on MDA-MB-231 cells proliferation were determined using Cell Counting Kit-8 and 5-Ethynyl-2'-deoxyuridine assays after Lentiviral transfection of MDA-MB-231. In addition, potential interaction partners of TRPC5OS were explored using liquid chromatography-mass spectrometry (LC-MS)/MS. Gene expression patterns following TRPC5OS overexpression were also detected in MDA-MB-231 cells by using High-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis were then used to systematically verify the potential interactions among the TRPC5OS-regulated genes. The potential relationship between TRPC5OS-interacting proteins and gene expression patterns were studied using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis. TRPC5OS expression was found to be significantly higher in TNBC tumour tissues and breast cancer cell lines compared with luminal tumour tissues and ZR-75-1. In addition, the overexpression of TRPC5OS significantly increased cell proliferation. High-throughput sequencing results revealed that 5,256 genes exhibited differential expression following TRPC5OS overexpression, including 3,269 upregulated genes and 1,987 downregulated genes. GO analysis results indicated that the functions of these differentially expressed genes were enriched in the categories of 'cell division' and 'cell proliferation' regulation. KEGG analysis showed that the TRPC5OS-regulated genes were associated with processes of 'homologous recombination' and 'TNF signalling pathways'. Subsequently, 17 TRPC5OS-interacting proteins were found using LC-MS/MS and STRING analysis. The most important protein among interacting proteins was ENO1 which was associated with glycolysis and regulated proliferation of cancer. In summary, data from the present study suggest that TRPC5OS overexpression can increase TNBC cell proliferation and ENO1 may be a potential target protein mediated by TRPC5OS. Therefore, TRPC5OS may serve as a novel therapeutic target for TNBC.

TRPC5OS induces tumorigenesis by increasing ENO1-mediated glucose uptake in breast cancer.

Breast cancer is the most common malignant tumor worldwide and the leading cause of cancer-related deaths in female. Metabolic reprogramming plays critical roles in breast tumorigenesis and induces enhanced glucose uptake and glycolysis. TRPC5OS is encoded by short transient receptor potential channel 5 opposite strand, and predicted to correlate with tumor metabolic reprogramming. Here we aim to elucidate the function of TRPC5OS in aberrant metabolism mediated tumorigenesis. We detected TRPC5OS expression levels in cell lines and tissues by quantitative real-time polymerase chain reaction and immunohistochemistry. Then we assessed the effects of TRPC5OS on proliferation and cell cycle progression in breast cancer cells by cell counting kit-8, colony-formation, EdU-incorporation assays and flow cytometry. Tumor growth in vivo was observed in a mouse xenograft model. Mass spectrum analyses were performed to identify potential interactors of TRPC5OS in tumor cells, and the interaction between TRPC5OS and interactors was validated by co-immunoprecipitation (CO-IP), western blots, and immunofluorescent staining. Glucose uptake was measured by liquid scintillation spectrometry. TRPC5OS highly expresses both in breast tumors and cell lines, and might be an independent prognostic marker for breast cancer patients. Overexpressed TRPC5OS promotes breast cancer cell proliferation, cell cycle progression, and enhances tumor xenograft growth. Mass spectral and CO-IP data showed that TRPC5OS interacts with ENO1. We also demonstrate that TRPC5OS could enhance ENO1/PI3K/Akt-mediated glucose uptake in breast cancer cells. Our study demonstrated that TRPC5OS promotes breast tumorigenesis by ENO1/PI3K/Akt-mediated glucose uptake. TRPC5OS might be an independent prognostic marker and potential therapeutic target for breast cancer patients.

Diagnostic and prognostic predictive values of circulating sTREM-1 in sepsis: A meta-analysis.

BACKGROUND: With the increasing studies regarding the diagnostic value of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in sepsis in recent years, it is essential to make an updated meta-analysis to explore the sepsis differentiation value of circulating sTREM-1 from systemic inflammatory response syndrome (SIRS). Recently, no meta-analysis was made to explore the prognostic predictive value of circulating sTREM-1 in sepsis. Thus, the present aimed to make meta-analyses to explore the diagnostic and prognostic predictive values of circulating sTREM-1 in sepsis. METHODS: Articles published before March 2021 were searched in databases: PubMed, Web of Science, EMBASE, Medline and Google Scholar. After a summary of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR), the receive-operating characteristics (SROC) curve were performed to summarize true positive (TP) and false positive (FP) rates. Q test and I2 were used to explore heterogeneity between studies. RESULTS: Circulating sTREM-1 showed a high sensitivity (0.85 (95% confidence interval (CI): 0.76-0.91)) and moderate specificity (0.79 (95% CI: 0.70-0.86)) to differentiate sepsis from SIRS. The study showed a high sensitivity (0.80 (95% CI: 0.66-0.89)) and moderate specificity (0.75 (95% CI: 0.69-0.81)) to predict 28-day mortality in sepsis. CONCLUSION: In conclusion, the present study suggested that circulating sTREM-1 showed diagnostic and prognostic predictive values in sepsis.

The use of trastuzumab affected by health insurance policy in Jiangsu Province of China.

BACKGROUND: Breast cancer recurrence and mortality have been shown to decrease after trastuzumab treatment in human epidermal growth factor 2 (HER2)-positive early-stage breast cancer (EBC) patients. In Jiangsu Province, trastuzumab has been subsidized for patients with HER2-positive EBC since 2013. Several studies showed that Jiangsu was one of the provinces with the highest rates of adjuvant trastuzumab therapy. To uncover the underlying reason, we designed the study to investigate trastuzumab use for HER2-positive breast cancer patients, and to examine the changes caused by medical insurance coverage for trastuzumab in Jiangsu province of China. METHODS: This was a retrospective, multicenter clinical study with follow-up data. HER2-positive EBC patients diagnosed in 7 representative hospitals in 2010, 2011, and 2013 were enrolled. Demographic and clinical data, and details of diagnosis, treatments, and prognosis, were collected. Data analysis included univariate analysis, multivariate logistic regression, survival analysis, and subgroup analysis. RESULTS: Of the 641 patients (mean age 51.01±10.79 years) included, 412 (64.27%) patients had medical insurance. Trastuzumab therapy was given to 214 (33.39%) patients. The multivariate logistic regression showed that medical insurance coverage, age, and radiotherapy were associated with trastuzumab use (P<0.05). The overall survival was significantly better in the trastuzumab group than in the non-trastuzumab group (HR: 1.607; 95% CI: 1.046-2.469; P=0.040). Subgroup analysis revealed that there was a trend towards more patients with medical insurance (P=0.073), and significantly more patients received trastuzumab therapy (P<0.001) in 2013 than in 2010-2011. Additionally, trastuzumab use in China was lower than in developed countries. Patients with medical insurance were more likely to use trastuzumab, and more patients could afford trastuzumab therapy with the development of China's health-care reform. CONCLUSIONS: Our study suggested that the percentage of patients who received trastuzumab in China was lower than developed countries. Patients who had medical insurance were more likely to use trastuzumab than those without medical insurance. The health insurance policy in China has improved access for breast cancer patients who require trastuzumab therapy.

Changes of lymphatic flow caused by core needle biopsy of axillary sentinel lymph node in a rabbit model.

BACKGROUND: Core needle biopsy (CNB) plays an important role in the preoperative axillary lymph node (ALN) assessment in breast cancer (BC) patients with the development of treatment, but little is known about the axillary lymph flow after CNB of ALNs. This study aimed to investigate the changes of lymphatic flow after CNB of sentinel lymph node (SLN) in a rabbit model. METHODS: The axillary SLN was biopsied in a rabbit model, and the changes of sentinel lymph flow were observed by methylthioninium chloride imaging at 1 and 12 days after the biopsy. Furthermore, the afferent lymphatic vessel was ligated and imaged once every 3 days to assess the changes of lymphatic flow. RESULTS: The SLN biopsied was characterized by disorganized medullary sinus containing erythrocytes, whereas clean medullary sinus containing a normal population of circulating lymphoid cells was observed in the contralateral normal SLN. At 1 day after biopsy, the sentinel lymphatic drainage was blocked. At 12 days after biopsy, the sentinel lymphatic flow was reconstructed or repaired. Ligation of afferent lymphatic vessel further confirmed the reconstruction of lymphatic flow. CONCLUSIONS: The sentinel lymphatic flow changes after CNB in a rabbit model, but it can be reconstructed or repaired.

The ability of an improved qSOFA score to predict acute sepsis severity and prognosis among adult patients.

This study analyzed independent risk factors that could improve the qSOFA scoring system among sepsis patients.This retrospective study evaluated 821 patients (2015-2016) who fulfilled the 2001 International Sepsis Definitions Conference diagnostic criteria. Patients were classified based on their survival outcomes after 28 days, and the predictive values of various predictive scores at admission were compared.The independent risk factors for 28-day mortality were fibrinogen, plasma lactic acid, albumin, oxygenation index, and procalcitonin level >0.5 ng/mL (all P < .05). The "PqSOFA" score combined the qSOFA score with procalcitonin, which provided an area under the curve value of 0.751 (95% CI: 0.712-0.790) for predicting 28-day mortality. A cut-off score of 2 points provided sensitivity of 83.2%, specificity of 54.9%, negative predictive value (NPV) of 33.03%, positive predictive value (PPV) of 92.47%, positive-likelihood ratio (PLR) of 1.85, and negative-likelihood ratio (NLR) of 0.31. The area under the curve for predicting 28-day mortality was significantly greater for the PqSOFA score than for the qSOFA score (Z = 7.019, P < .0001). The PqSOFA score was comparable to the SOFA and APACHE II scores.The PqSOFA score independently predicted poor short-term outcomes among high-risk sepsis patients.

Serum tRNA-derived fragments (tRFs) as potential candidates for diagnosis of nontriple negative breast cancer.

Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non-TNBC) accounts for 80-90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA-derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high-throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non-TNBC. Furthermore, quantitative reverse-transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR-7816, tDR-5334, and tDR-4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR-7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR-7816 expression as a novel potential biomarker for the diagnosis of patients with early non-TNBC.

Thrombo-inflammatory prognostic score improves qSOFA for risk stratification in patients with sepsis: a retrospective cohort study.

Background Both the thrombo-inflammatory prognostic score (TIPS) and the quick sequential (sepsis-related) organ failure assessment (qSOFA) are quick prognostic scores for sepsis during the early phase, while either of two scores has limited prognostic value for sepsis patients. This study aimed to evaluate whether TIPS adds more information of sepsis risk stratification for qSOFA. Methods This was a retrospective cohort study of patients with sepsis in the emergency department (ED). We performed a receiver-operating characteristic curve, integrated discrimination improvement (IDI), net reclassification improvement (NRI) and decision-curve analysis (DCA) analyses to investigate whether TIPS can improve qSOFA for risk prediction in patients with sepsis. The primary endpoint was mortality and the secondary endpoints were mechanical ventilation and admission to the intensive care unit (ICU) during the 28-day follow-up. Results We identified 821 patients with sepsis. We randomly assigned the patients' data to a derivation group (n = 498; n = 112 died during the 28-days follow-up) or to a validation group (n = 323; n = 61). The addition of TIPS to qSOFA (T-qSOFA) improved the area under the curve (AUC) from 0.724 to 0.824 (p < 0.001) for predicting 28-day mortality. The discrimination improvement was confirmed by an IDI of 0.092 (p < 0.001). Addition of TIPS to the qSOFA resulted in a NRI of 0.247 (p < 0.001). The DCA showed that the net benefit of T-qSOFA was higher than that of TIPS or qSOFA for any threshold probabilities. Conclusions The prognostic value of qSOFA for patients with sepsis was enhanced by adding the TIPS score on admission for risk prediction in patients with sepsis during early phases in the ED.

ZFP57 suppress proliferation of breast cancer cells through down-regulation of MEST-mediated Wnt/ß-catenin signalling pathway.

Activation of oncogenes by promoter hypomethylation plays an important role in tumorigenesis. Zinc finger protein 57 (ZFP57), a member of KRAB-ZFPs, could maintain DNA methylation in embryonic stem cells (ESCs), although its role and underlying mechanisms in breast cancer are not well understood. In this study, we found that ZFP57 had low expression in breast cancer, and overexpression of ZFP57 could inhibit the proliferation of breast cancer cells by inhibiting the Wnt/ß-catenin pathway. MEST was validated as the direct target gene of ZFP57 and MEST may be down-regulated by ZFP57 through conserving DNA methylation. Furthermore, overexpression of MEST could restore the tumour-suppressed and the Wnt/ß-catenin pathway inactivated effects of ZFP57. ZFP57-MEST and the Wnt/ß-catenin pathway axis are involved in breast tumorigenesis, which may represent a potential diagnostic biomarker, and provide a new insight into a novel therapeutic strategy for breast cancer patients.

Hypoxia-induced tRNA-derived fragments, novel regulatory factor for doxorubicin resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA-derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia-treated TNBC cell lines through the use of high-throughput sequencing technique. Quantitative real-time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR-0009 [derived from transfer RNA (tRNA)Gly-GCC-1-1 ] and tDR-7336 (derived from tRNA Gly-GCC-1-2 ) were significantly upregulated when the SUM-1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)-6, which may be the underlying mechanism of hypoxia-induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein-protein interaction network for predicted target genes established by the STRING database manifested that tDR-0009 (tDR-7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia-treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia-induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets.

Evaluation of a novel prognostic score based on thrombosis and inflammation in patients with sepsis: a retrospective cohort study.

BACKGROUND: Inflammation and thrombosis are involved in the development and progression of sepsis. A novel thrombo-inflammatory prognostic score (TIPS), based on both an inflammatory and a thrombus biomarker, was assessed for its ability to predict adverse outcomes of sepsis patients in the emergency department (ED). METHODS: This was a retrospective cohort study of sepsis patients. TIPS (range: 0-2) was predictive of adverse outcomes. Multivariable logistic regression analyses were performed to investigate the associations between TIPS and 28-day adverse outcomes. The study end points were mortality, mechanical ventilation (MV), consciousness disorder (CD) and admission to the intensive care unit (AICU). RESULTS: In total, 821 sepsis patients were enrolled; 173 patients died within the 28-day follow-up period. Procalcitonin and D-dimer values were used to calculate TIPS because they had the best performance in the prediction of 28-day mortality by receiver operating characteristic curves. The 28-day mortality and the incidence of MV, CD and AICU were significantly higher in patients with higher TIPS. Multivariable logistic regression analysis indicated TIPS was an independent predictor of 28-day mortality, MV and AICU. TIPS performed better than other prognostic scores, including quick sequential organ failure assessment, Modified Early Warning Score and Mortality in Emergency Department Sepsis Score for predicting 28-day mortality, and similar to the Acute Physiology and Chronic Health Evaluation II, but inferior to sequential organ failure assessment. CONCLUSIONS: TIPS is useful for stratifying the risk of adverse clinical outcomes in sepsis patients shortly after admission to the ED.

Clinical study of a new Modified Early Warning System scoring system for rapidly evaluating shock in adults.

OBJECTIVE: Shock, the most common severe emergency syndrome, has a complicated etiopathogenesis, is difficult to identify, progresses quickly, and is dangerous. Early identification and intervention play determining roles in the final outcomes of shock patients, but no specific scoring system for shock has been established to date. METHODS: We collected 292 shock patients and analyzed the correlation between 28-day prognosis and the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II), Modified Early Warning System (MEWS), and Sequential Organ Failure Assessment scoring systems. According to the previous result, we established a new MEWS scoring system based on the conventional MEWS, which also included age and transcutaneous oxygen saturation. Some of the items with a strong correlation with the 28-day prognosis were selected to establish the new MEWS scoring system. We then evaluated the predictive efficacy of the new MEWS scoring system on 28-day prognosis and the correlation with other scoring systems. RESULTS: Some indexes, including age, transcutaneous oxygen saturation, arterial blood pH and blood lactic acid, serum sodium, serum potassium, HCO3, and red blood cells deposited, differed significantly between the nonsurviving and surviving groups (P<.05). The area under the curve (AUC) of the APACHE II, MEWS, shock index, and Sequential Organ Failure Assessment scoring systems for 28-day prognosis indicated a critical predictive efficacy. Receiver operating characteristic curves indicated that the MEWS AUC was 0.614, new MEWS AUC was 0.696, and APACHE II AUC was 0.785, suggesting superiority of the new MEWS to the conventional MEWS but inferiority to the APACHE II. Interestingly, the correlation efficient of the traditional MEWS and the new MEWS was 0.81. The correlation efficient of these scoring systems with other indexes, including lactic acid and hemoglobin, was less than 0.3. CONCLUSIONS: The new MEWS scoring system could be an independent indicator to reflect shock severity. It has higher predictive efficacy in septic shock, especially for 28-day prognosis.