An externally validated prognostic model for critically ill patients with traumatic brain injury.

OBJECTIVE: Patients with traumatic brain injury (TBI) who are admitted to the intensive care unit often exhibit critical conditions; thus, early prediction of in-hospital mortality is crucial. In this study, we aimed to develop a reliable and easily promotable model for predicting the in-hospital mortality of critically ill patients with TBI using easily accessible indicators and validate the model using external data. METHODS: Patient data from the Medical Information Mart for Intensive Care-IV 2.2 database were used as training and internal validation sets to establish and internally validate the prognostic model. Data from the Affiliated Dongyang Hospital of Wenzhou Medical University were used for external validation. The Boruta algorithm was used for the initial feature selection, followed by univariate and multivariate logistic regression analyses to identify the final independent predictors. The predictive performance was evaluated using a receiver operating characteristic curve, calibration curve, clinical practicality decision curve analysis, and clinical impact curve. RESULTS: This study included 3225 patients (training set: 2042; internal validation set: 874; and external validation set: 309). Ten variables were selected for inclusion in the nomogram model: age, mechanical ventilation usage, vasoactive agent usage, intracerebral hemorrhage, temperature, respiration rate, white blood cell count, platelet count, red blood cell distribution width, and glucose. The nomogram demonstrated good predictive performance in both the internal and external validation sets. INTERPRETATION: We developed an externally validated nomogram that exhibited good discrimination, calibration, and clinical utility for predicting in-hospital mortality in critically ill patients with TBI.

Development and validation of a web-based predictive model for preoperative diagnosis of localized colorectal cancer and colorectal adenoma.

Background: Localized colorectal cancer (LCC) has obscure clinical signs, which are difficult to distinguish from colorectal adenoma (CA). This study aimed to develop and validate a web-based predictive model for preoperative diagnosis of LCC and CA. Methods: We conducted a retrospective study that included data from 500 patients with LCC and 980 patients with CA who were admitted to Dongyang People's Hospital between November 2012 and June 2022. Patients were randomly divided into the training (n=1036) and validation (n=444) cohorts. Univariate logistic regression, least absolute shrinkage and selection operator regression, and multivariate logistic regression were used to select the variables for predictive models. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance of the model. Results: The web-based predictive model was developed, including nine independent risk factors: age, sex, drinking history, white blood cell count, lymphocyte count, red blood cell distribution width, albumin, carcinoembryonic antigen, and fecal occult blood test. The AUC of the prediction model in the training and validation cohorts was 0.910 (0.892-0.929) and 0.894 (0.862-0.925), respectively. The calibration curve showed good consistency between the outcome predicted by the model and the actual diagnosis. DCA and CIC showed that the predictive model had a good clinical application value. Conclusion: This study first developed a web-based preoperative prediction model, which can discriminate LCC from CA and can be used to quantitatively assess the risks and benefits in clinical practice.

Development and validation of a prediction model for in-hospital mortality of patients with severe thrombocytopenia.

Risk stratification and prognosis evaluation of severe thrombocytopenia are essential for clinical treatment and management. Currently, there is currently no reliable predictive model to identify patients at high risk of severe thrombocytopenia. This study aimed to develop and validate a prognostic nomogram model to predict in-hospital mortality in patients with severe thrombocytopenia in the intensive care unit. Patients diagnosed with severe thrombocytopenia (N = 1561) in the Medical Information Mart for Intensive Care IV database were randomly divided into training (70%) and validation (30%) cohorts. In the training cohort, univariate and multivariate logistic regression analyses with positive stepwise selection were performed to screen the candidate variables, and variables with p < 0.05 were included in the nomogram model. The nomogram model was compared with traditional severity assessment tools and included the following 13 variables: age, cerebrovascular disease, malignant cancer, oxygen saturation, heart rate, mean arterial pressure, respiration rate, mechanical ventilation, vasopressor, continuous renal replacement therapy, prothrombin time, partial thromboplastin time, and blood urea nitrogen. The nomogram was well-calibrated. According to the area under the receiver operating characteristics, reclassification improvement, and integrated discrimination improvement, the nomogram model performed better than the traditional sequential organ failure assessment (SOFA) score and simplified acute physiology score II (SAPS II). Additionally, according to decision curve analysis, a threshold probability between 0.1 and 0.75 indicated that our constructed nomogram model showed more net benefits than the SOFA score and SAPS II. The nomogram model we established showed superior predictive performance and can assist in the quantitative assessment of the prognostic risk in patients with severe thrombocytopenia.

Revisit the Cellular Transmission and Emerging Techniques in Understanding the Mechanisms of Proteinopathies.

Alzheimer's and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aß) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aß and α-synuclein in mediating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

The Relationship Between Prognostic Nutritional Index and All-Cause Mortality in Critically Ill Patients: A Retrospective Study.

PURPOSE: The effectiveness and prognostic value of the prognostic nutritional index (PNI) in critically ill patients are unknown. Hence, this study aimed to analyze the relationship between the PNI and all-cause mortality in critically ill patients. PATIENTS AND METHODS: Patient data were obtained from the Multiparameter Intelligent Monitoring in Intensive Care III database. The relationship between the PNI and in-hospital mortality was analyzed using receiver operating characteristic curve analysis and a logistic regression model. Propensity score matching (PSM) was used to eliminate the bias caused by confounding factors. The Kaplan-Meier curve and Cox regression model were used to test the effect of the PNI on 30-, 90-, 180-, and 365-day mortality. RESULTS: A low PNI score is an independent risk factor for in-hospital mortality in critically ill patients. A total of 3644 cases were successfully matched using PSM. The PSM group with balanced covariates obtained similar results in the three models, which were statistically significant. The Kaplan-Meier curve and Cox regression model showed that the PNI was negatively correlated with 30-, 90-, 180-, and 365-day all-cause mortality. CONCLUSION: The PNI score is an independent risk factor for all-cause mortality in critically ill patients, where a low PNI score is associated with increased mortality.

Rapid and high selective removal of Hg(II) ions using tannic acid cross-linking cellulose/polyethyleneimine functionalized magnetic composite.

In this study, a new tannic acid cross-linking cellulose/polyethyleneimine functionalized magnetic composite (MCP) as a biomass adsorbent of Hg(II) ions was prepared. The morphology and structure of MCP were characterized with FT-IR, TG, XRD, SEM and TEM. The effect of the different factors such as pH, contact time, initial Hg(II) ion concentration, and adsorption temperature on the adsorption behavior was investigated. The results showed that MCP exhibited an excellent selectivity and reutilization, fast removal rate, and very high adsorption capacity. The corresponding adsorption capacity and removal rate of could reach 99.00% and 247.51 mg/g when the pH value, adsorption time, Hg(II) ion concentration were 5, 180 min and 100 mg/L at 293 K. The kinetics followed the pseudo-second-order, which indicated that the adsorption behavior of MCP for Hg(II) ion belonged to the chemical adsorption process and external diffusion. The thermodynamic study showed that the adsorption process was a spontaneous and exothermic process. After the fifth adsorption-desorption experiment, it still had better adsorption performance and reutilization. All in all, MCP with highly stable and efficient, as well as excellent reusability will be a candidate for industry-level applications from wastewater with Hg(II) ions.

MicroRNA-96 is required to prevent allodynia by repressing voltage-gated sodium channels in spinal cord.

Voltage-gated sodium channels (Navs) 1.7, 1.8, and 1.9 are predominately expressed in peripheral sensory neurons and are critical for action potential propagation in nociceptors. Unexpectedly, we found that expression of SCN9A, SCN10A, SCN11A, and SCN2A, the alpha subunit of Nav1.7, Nav1.8, Nav1.9 and Nav1.2, respectively, are up-regulated in spinal dorsal horn (SDH) neurons of miR-96 knockout mice. These mice also have de-repression of CACNA2D1/2 in DRG and display thermal and mechanical allodynia that could be attenuated by intrathecal or intraperitoneal injection of Nav1.7 or Nav1.8 blockers or Gabapentin. Moreover, Gad2::CreERT2 conditional miR-96 knockout mice phenocopied global knockout mice, implicating inhibitory neurons; nerve injury induced significant loss of miR-96 in SDH GABAergic and Glutamatergic neurons in mice which negatively correlated to up-regulation of Nav1.7, Nav1.8, Nav1.9 and Scn2a, this dis-regulation of miR-96 and Navs in SDH neurons contributed to neuropathic pain which can be alleviated by intrathecal injection of Nav1.7 or Nav1.8 blockers. In conclusion, miR-96 is required to avoid allodynia through limiting the expression of VGCCs and Navs in DRG and Navs in SDH in naïve and nerve injury-induced neuropathic pain mice. Our findings suggest that central nervous system penetrating Nav1.7 and Nav1.8 blockers may be efficacious for pain relief.

The clinicopathological and prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in small cell lung cancer: A meta-analysis.

Although many scholars have recently studied the relationships between the pretreatment neutrophil-to-lymphocyte ratio (NLR) and prognosis in patients with small cell lung cancer (SCLC), the conclusions have been inconsistent. Accordingly, in this meta-analysis, we attempted to assess the clinicopathological and prognostic value of the pretreatment NLR in SCLC. Related literature was searched using PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Each eligible study was extracted, and a meta-analysis was performed using hazard ratios (HRs) and 95% confidence intervals (95% CIs) to assess the prognostic value of NLR. Evaluation of the clinicopathological significance of NLR in SCLC used odds ratios (ORs) and 95% confidence intervals (95% CIs). We included a total of 20 studies with 21 outcomes (5141 patients) in this meta-analysis. The results showed that high pretreatment NLR was closely related to poorer progression free survival (PFS) and overall survival (OS) (PFS, HR = 1.55, 95% CI = 1.27-1.88, P < 0.0001; I2 = 0%; OS, HR = 1.40, 95% CI = 1.26-1.55, P < 0.00001; I2 = 64%). In addition, pretreatment NLR was significantly associated with clinical stage of SCLC (OR = 2.14, 95% CI = 1.35-3.39, P = 0.001). Our meta-analysis showed that high levels of pretreatment NLR were significantly associated with a more serious clinical stage and poorer PFS and OS in SCLC.

The association of D-dimer with clinicopathological features of breast cancer and its usefulness in differential diagnosis: A systematic review and meta-analysis.

BACKGROUND: Studies have shown that D-dimer levels are significantly correlated with the differential diagnosis and clinicopathological features of breast cancer. However, the results are currently limited and controversial. Therefore, we performed this meta-analysis to evaluate the relationship between D-dimer levels and breast cancer. MATERIALS AND METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang databases were searched to find studies that assessed the association of D-dimer with clinicopathological features of breast cancer and its usefulness in aiding with differential diagnosis. The standardized mean difference (SMD) was applied as the correlation measure. RESULTS: A total of 1244 patients with breast cancer from 15 eligible studies were included in the meta-analysis. D-dimer levels were higher in the breast cancer group than in the benign (SMD = 1.02; 95% confidence interval [CI] = 0.53-1.52) and healthy (SMD = 1.27; 95% CI = 0.85-1.68) control groups. In addition, elevated D-dimer levels were associated with progesterone receptor-negative tumors (SMD = -0.25; 95% CI = -0.44--0.05). Similarly, there was a significant correlation between D-dimer levels and tumor node metastasis staging (n = 11, SMD = 0.82; 95% CI = 0.57-1.06) and lymph node involvement (n = 8, SMD = 0.79; 95% CI = 0.50-1.09). In contrast, other clinicopathological factors, including estrogen receptor expression and human epidermal growth factor receptor 2 expression, were not associated with D-dimer levels. CONCLUSION: The results of this meta-analysis indicate that plasma D-dimer levels can be used as an important reference for the early identification and staging of breast cancer.

Role of Vascular Endothelial-Cadherin and p120-Catenin in the Formation of Experimental Intracranial Aneurysm in Animals.

BACKGROUND: Dysfunction of endothelial cells (ECs) constitutes a critical factor in the formation of intracranial aneurysms (IAs). However, little is known about the response of ECs to hemodynamic insults and its contribution to IA formation. METHODS: IAs models were constructed in both adult female New Zealand white rabbits and male Sprague-Dawley rats. Morphologic changes of vessel wall were detected by hematoxylin and eosin staining. Molecular and cellular changes, including p120-catenin (p120ctn) and vascular endothelial-cadherin, in the median sagittal section of the artery bifurcation were analyzed by fluorescent staining. RESULTS: Destructive aneurysmal remodeling and the formation of morphologic IAs were observed at the basilar termini of experimental rabbits and the anterior cerebral artery-olfactory artery bifurcation of rats. The expression of p120ctn colocalized with vascular endothelial-cadherin in ECs decreased. Moreover, the expression of p120ctn colocalized with nucleus of ECs increased. These events suggested that p120ctn was transported from the membrane to the nucleus of ECs. CONCLUSIONS: The potential mechanism, that IAs are always localizing in the bifurcation apices, may be that the endothelium injury of vessel wall can be induced by different hemodynamic conditions. Hemodynamic changes in artery bifurcation may initiate the formation of IAs.

Knockdown of P120 catenin aggravates endothelial injury under an impinging flow by inducing breakdown of adherens junctions.

At present, the mechanisms underlying intracranial aneurysm (IA) development remain unclear; however, hemodynamics is considered a crucial factor in the induction of IA. To elucidate the association between hemodynamics and endothelial cell (EC) functions, a modified T chamber system was designed to simulate the adjustable hemodynamic conditions of an artery bifurcation. Normal human umbilical vein ECs (HUVECs) and HUVECs with P120 catenin (P120ctn) knockdown were cultured on coverslips and placed in the chamber. A flow rate of 250 or 500 ml/min impinged on the cell layer. Subsequently, the expression levels of P120ctn and other proteins, and EC morphological alterations, were examined. In normal HUVECs, after 3 h under a flow rate of 500 ml/min, the expression levels of P120ctn, vascular endothelial (VE)­Cadherin, Kaiso and α­catenin were decreased, whereas matrix metalloproteinase­2 (MMP­2) was increased. In HUVECs with P120ctn knockdown, the period during which ECs adhered to the coverslip was reduced to 1 h under a flow rate of 500 ml/min. In addition, the expression levels of VE­Cadherin, Kaiso and α­catenin in ECs were decreased, whereas those of MMP­2 were increased after 1 h; more prominent alterations were detected under a 500 ml/min flow rate compared with a 250 ml/min flow rate. Adherens junctions (AJs) are critical to the maintenance of normal morphology and EC functioning in the vascular wall, and P120ctn is an important regulator of AJs. Loss of P120ctn may be induced by hemodynamic alterations. In response to changes in hemodynamic conditions, a loss of P120ctn may aggravate AJs between ECs, thus inducing inflammation in the vascular wall. Clinically, hemodynamic alterations may result in a loss of P120ctn and endothelial injury; therefore, P120ctn may have a critical role in inducing intracranial aneurysms.

Effects of preadmission beta-blockers on neurogenic stunned myocardium after aneurysmal subarachnoid hemorrhage: A meta- analysis.

OBJECTIVE: Spontaneous subarachnoid hemorrhage is mostly caused by the rupture of an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads to subendocardial ischemia or coronary artery spasm. We designed this meta-analysis to find out whether beta-blockers (BB) can significantly reduce the incidence of NSM and improve the outcomes of aSAH. PATIENTS AND METHODS: We systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline from inception to Feb 2016. All studies related to the preadmission beta-blocker with aSAH were included. RESULTS: Three retrospective studies and 691 patients were included. The incidence of mortality [OR=0.68, 95%CI (0.08-3.50), P=0.57], cardiac dysfunction [OR = 0.55, 95% CI (0.05-6.49), P=0.63], cerebral vasospasm (OR=0.52 95% CI(0.18-2.56), P=0.50] had no statistical difference between the preadmission BB group and no BB group. CONCLUSION: The preadmission beta-blocker cannot decrease the incidence of mortality, cardiac dysfunction, cerebral vasospasm in patients with aSAH. A further research of the usefulness of preadmission beta-blocker in patients with aSAH will be needed.

Pleural fluid prealbumin and C-reactive protein in the differential diagnosis of infectious and malignant pleural effusions.

Clinical history and physical examination are helpful in indicating the potential causes of pleural effusions (PEs). However, the accurate diagnosis and establishment of the causes of PE is an ongoing challenge in daily clinical practice. The primary aim of this study was to distinguish between infectious PE and malignant PE (MPE) by measuring two major acute phase response biomarkers: prealbumin (PA) and C-reactive protein (CRP). The study was a prospective trial involving 151 patients who were diagnosed with infectious PE or MPE. Patients with infectious PE were divided into two subgroups: tuberculous PE (TBPE) and parapneumonic PE (PNPE). A further 58 patients with PEs that showed no evidence of MPE, TBPE or PNPE were classified as the chronic non-specific PE (NSPE) group. Demographic characteristics and pleural fluids of the subjects were collected consecutively. The discriminative properties of pleural fluid routine biochemistries, and PA and CRP were evaluated. PA, CRP and classical fluid parameters were also applied to classify patients with infectious PE and MPE. Receiver operating characteristics (ROC) analysis established the cutoffs of PA and CRP for discriminating between groups. Pleural fluid PA levels were significantly higher in the MPE group (n=47) than in the infectious PE group (n=104). Pleural fluid CRP levels were significantly higher in the infectious PE group than in the MPE group. Pleural fluid PA levels were identified to be moderately negatively correlated with CRP levels in the MPE group, with a statistically significant correlation coefficient of -0.352. The ROC curve showed that the sensitivity and specificity of PA for the diagnosis of MPE were 0.851 and 0.548, respectively, at the cutoff of 28.3 mg/l. The area under the curve (AUC) was 0.784 (95% CI, 0.707-0.861). Using CRP as a diagnostic parameter resulted in an comparable AUC of 0.810 (95% CI, 0.736-0.885), at the cutoff of 35.2 mg/l. Combinations of PA and CRP resulted in incrementally discriminating values for MPE, with a sensitivity of 0.617 and a specificity of 0.903. The measurement of PA and CRP levels in pleural fluid may be a useful adjunctive test in PE, as a potential differentiator between infectious PE and MPE.