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Background: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients, necessitating reliable prognostic tools. The segmented neutrophil-to-monocyte (SeMo) ratio, indicative of the inflammatory response, has emerged as a valuable biomarker. This study evaluates the prognostic value of dynamic changes in the SeMo ratio in predicting outcomes for patients with moderate to severe TBI. Methods: A retrospective analysis was conducted on data from 1118 TBI patients admitted to the surgical intensive care unit at a level I trauma center between January 2009 and December 2020. Patients were selected based on an Abbreviated Injury Scale (AIS) score ≥ 3 in the head region. Initial and follow-up SeMo ratios were calculated upon admission and 48–72 h later, respectively. The dynamic SeMo ratio was defined as the difference between the second and initial SeMo ratios. Statistical analyses included receiver operating characteristic (ROC) curve analysis to determine the optimal threshold for mortality prediction, and comparative analysis of clinical outcomes. Results: The study cohort included 121 deceased and 997 surviving patients. Deceased patients had significantly higher second SeMo ratios (20.9 ± 16.1 vs. 15.8 ± 17.2, p = 0.001) and dynamic SeMo ratios (2.4 ± 19.8 vs. −2.1 ± 19.5, p = 0.019) than those survival patients. In the multivariate analysis, the dynamic SeMo is a significant independent risk factor for in-hospital mortality (OR 1.01, 95%CI: 1.01–1.03, p = 0.031). The optimal cut-off for the dynamic SeMo ratio was 5.96, above which patients exhibited higher mortality (21.4% vs. 8.5%, p < 0.001), higher adjusted mortality (adjusted odds ratio: 2.98; 95% confidence interval: 1.95–4.56; p = 0.005), and longer hospital stays (23.6 days vs. 19.7 days, p = 0.005). Discussion: Dynamic SeMo ratio changes serve as a prognostic marker for in-hospital mortality and hospital stay duration in moderate to severe TBI patients. A higher dynamic SeMo ratio indicates increased risk, highlighting the importance of early monitoring and intervention. Future prospective studies should validate these findings and explore integration with other biomarkers for enhanced prognostication.

IntroductionThe easy albumin-bilirubin (EZ-ALBI) score is calculated using the equation: total bilirubin (mg/dl) − 9 × albumin (g/dl), and is used to evaluate liver functional reserve. This study was designed to investigate whether the EZ-ALBI score serves as an independent risk factor for mortality and is useful for stratifying the mortality risk in adult trauma patients.MethodsWe retrospectively reviewed data from the registered trauma database of the hospital and included 3,637 adult trauma patients (1,241 deaths and 2,396 survivors) due to all trauma caused between January 1, 2009, and December 31, 2021. The patients were allocated to the two study groups based on the best EZ-ALBI cutoff point (EZ-ALBI = −28.5), which was determined based on the area under the receiver operating characteristic curve.ResultsResults revealed that the non-survivors had a significantly higher EZ-ALBI score than the survivors (−26.4 ± 6.5 vs. −31.5 ± 6.2, p

Background: The Stress Index (SI), calculated as the ratio of blood glucose to serum potassium levels, is a promising prognostic marker in various acute care settings. This study aimed to evaluate the utility of the SI for predicting mortality in patients with isolated moderate-to-severe traumatic brain injury (TBI). Methods: This retrospective cohort study included adult trauma patients (aged ≥ 20 years) with isolated moderate to severe TBI (Abbreviated Injury Scale ≥ 3 for only head region) treated from 2009–2022. The SI was computed from the initial glucose and potassium levels upon arrival at the emergency department. Logistic regression models were used to assess the association between the SI and mortality after adjusting for relevant covariates. The most effective threshold value of the SI for predicting mortality was identified using receiver operating characteristic (ROC) analysis. Results: Among the 4357 patients with isolated moderate and severe TBI, 463 (10.6%) died. Deceased patients had a significantly higher SI (61.7 vs. 44.1, p < 0.001). In multivariate analysis, higher SI independently predicted greater mortality risk (odds ratio (OR) 6.70, 95% confidence interval (CI) 1.66–26.99, p = 0.007). The optimal SI cutoff for predicting mortality was 48.50 (sensitivity 62.0%, specificity 71.4%, area under the curve 0.724). Patients with SI ≥ 48.5 had nearly two-fold higher adjusted mortality odds compared to those below the threshold (adjusted OR 1.94, 95% CI 1.51–2.50, p < 0.001). Conclusions: SI is a useful predictor of mortality in patients with isolated moderate-to-severe TBI. Incorporating SI with standard clinical assessments could enhance risk stratification and management approaches for this patient population.

Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study’s findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis.

Background: Hyponatremia and hypokalemia are common electrolyte imbalances in trauma patients and have been identified to be risk factors for a fall. In addition, hyponatremia was reported to be related to osteoporosis and fragility fractures, while the association between hypokalemia and osteoporosis has only been reported in rare case reports. This study investigated the impact of hyponatremia and hypokalemia on the incidence of fractures in various body regions of adult trauma patients, using the propensity score-matched patient cohort to reduce the influence of patients’ baseline characteristics. Methods: The study analyzed data from 11,173 hospitalized adult trauma patients treated from 1 January 1998, to 31 December 2022. The study included 1968 patients with hyponatremia and 9205 without, and 1986 with hypokalemia and 9187 without. Different 1:1 propensity score-matched cohorts were generated to create the 1903 pairings of patients with or without hyponatremia, 1977 pairings of patients with or without hypokalemia, and 380 pairing of patients with both hyponatremia and hypokalemia vs. normal control patients. Analysis was conducted on the incidence of fracture in various anatomic regions. Results: Hyponatremic patients had increased odds of thoracic vertebral fracture [odds ratio (95% confidence interval) 1.63 (1.10–2.42), p = 0.014], pelvic fracture [2.29 (1.12–4.67), p = 0.019], and femoral fracture [1.28 (1.13–1.45), p < 0.001] but decreased odds of radial and patella fractures. Hypokalemic patients showed no significant differences in fracture risk except for a decreased likelihood of radial fractures. The patients with both hyponatremia and hypokalemia showed a decreased likelihood of radial fractures and patella fractures. Conclusion: Hyponatremia may have a greater impact on the occurrence of bone fractures than hypokalemia in trauma patients who have suffered a fall. Electrolyte abnormalities should be taken into account while assessing the risk of fractures in trauma patients.

Background: Blood immune cell subset alterations following trauma can indicate a patient′s immune–inflammatory status. This research explored the influence of stress-induced hyperglycemia (SIH) on platelet counts and white blood cell (WBC) subtypes, including the derived indices of the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in trauma patients. Methods: We studied 15,480 adult trauma patients admitted from 1 January 1998 to 31 December 2022. They were categorized into four groups: nondiabetic normoglycemia (NDN, n = 11,602), diabetic normoglycemia (DN, n = 1750), SIH (n = 716), and diabetic hyperglycemia (DH, n = 1412). A propensity score-matched cohort was formed after adjusting for age, sex, and comorbidities, allowing for comparing the WBC subtypes and platelet counts. Results: Patients with SIH exhibited significantly increased counts of monocytes, neutrophils, and lymphocytes in contrast to NDN patients. However, no significant rise in platelet counts was noted in the SIH group. There were no observed increases in these cell counts in either the DN or DH groups. Conclusions: Our results demonstrated that trauma patients with SIH showed significantly higher counts of monocytes, neutrophils, and lymphocytes when compared to NDN patients, whereas the DN and DH groups remained unaffected. This underscores the profound association between SIH and elevated levels of specific WBC subtypes.

The easy albumin–bilirubin (EZ–ALBI) score is derived using the following equation: total bilirubin (mg/dL) − 9 × albumin (g/dL). This study aimed to determine whether the EZ–ALBI score predicted mortality risk in adult trauma patients in an intensive care unit (ICU). Data from a hospital’s trauma database were retrospectively evaluated for 1083 adult trauma ICU patients (139 deaths and 944 survivors) between 1 January 2016 and 31 December 2021. Patients were classified based on the ideal EZ–ALBI cut-off of −26.5, which was determined via receiver operating characteristic curve analysis. The deceased patients’ EZ–ALBI scores were higher than those of the surviving patients (−26.8 ± 6.5 vs. −30.3 ± 5.9, p = 0.001). Multivariate logistic analysis revealed that, in addition to age, the presence of end-stage renal disease, Glasgow Coma Scale scores, and injury severity scores, the EZ–ALBI score is an independent risk factor for mortality (odds ratio (OR), 1.10; 95% confidence interval (CI): 1.06–1.14; p = 0.001)). Compared with patients with EZ–ALBI scores < −26.5, those with scores ≥ −26.5 had a 2.1-fold higher adjusted mortality rate (adjusted OR, 2.14; 95% CI: 1.43–3.19, p = 0.001). In conclusion, the EZ–ALBI score is a substantial and independent predictor of mortality and can be screened to stratify mortality risk in adult trauma ICU patients.

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.

Background. Malnutrition is prevalent among critically ill patients and has been associated with a poor prognosis. This study sought to determine whether the addition of a nutritional indicator to the various variables of prognostic scoring models can improve the prediction of mortality among trauma patients in the intensive care unit (ICU). Methods. This study’s cohort included 1,126 trauma patients hospitalized in the ICU between January 1, 2018, and December 31, 2021. Two nutritional indicators, the prognostic nutrition index (PNI), a calculation based on the serum albumin concentration and peripheral blood lymphocyte count, and the geriatric nutritional risk index (GNRI), a calculation based on the serum albumin concentration and the ratio of current body weight to ideal body weight, were examined for their association with the mortality outcome. The significant nutritional indicator was served as an additional variable in prognostic scoring models of the Trauma and Injury Severity Score (TRISS), the Acute Physiology and Chronic Health Evaluation (APACHE II), and the mortality prediction models (MPM II) at admission, 24, 48, and 72 h in the mortality outcome prediction. The predictive performance was determined by the area under the receiver operating characteristic curve. Results. Multivariate logistic regression revealed that GNRI (OR, 0.97; 95% CI, 0.96–0.99; p=0.007), but not PNI (OR, 0.99; 95% CI, 0.97–1.02; p=0.518), was independent risk factor for mortality. However, none of these predictive scoring models showed a significant improvement in prediction when the GNRI variable is incorporated. Conclusions. The addition of GNRI as a variable to the prognostic scoring models did not significantly enhance the performance of the predictors.

Background: Platelet-rich plasma (PRP) is beneficial for clinical applications in various medical fields. Although commercial PRP preparation kits are already available in the market, most of these kits employ centrifugation. Methods: We used a new cationic copolymer coating on a polyurethane (PU) sponge to promote platelet separation from the blood. This copolymer showed no cytotoxicity against cell viability or hemolysis. We further evaluated the efficiency of the new PRP preparation device by comparing it with that of a commercially available kit (RegenKit-THT). Results: We demonstrated that PRP obtained using copolymer device contains high concentrations of platelets and angiogenic growth factors (epidermal growth factor, vascular endothelial growth factor-A, growth differentiation factor 2, and interleukin-8). The separated PRP also displayed beneficial effects on cell migration, angiogenesis, and matrix metalloproteinase gene expression. Conclusion: Based on these results, we developed a cationic copolymer-coated PU sponge as a PRP preparation device without the need for any centrifugation.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified to play a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of the lncRNA-miRNA/mRNA network may yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for the next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there were different expressions of 34 transcripts (2 lncRNAs, XISTs, and MIR222HGs; 29 mRNAs; and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of lncRNA-XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA–miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells, particularly resting memory CD4+ T cells, and negative correlations in the infiltration of Th1 CD4+ T cells.

Introduction. Skull fractures are often found in patients with traumatic brain injury (TBI). Although skull fractures may indicate greater force impact and are associated with local or diffuse brain injuries, the prognostic value of skull fractures remains unclear. This retrospective study aimed to assess the association between skull fractures and mortality in patients with TBI. Methods. This study included 5,430 TBI patients registered in the trauma registry system from January 2009 to December 2018. Clinical and demographic data including age, sex, trauma mechanisms, comorbidities, Glasgow Coma Scale (GCS) score, abbreviated injury score (AIS)-head, injury severity score (ISS), and in-hospital mortality were acquired. Multiple logistic regression and propensity score matching were used to elucidate the effect of skull fractures on mortality outcomes of TBI patients. Results. Compared to TBI patients without skull fracture, patients with skull fractures were predominantly male, younger, had lower GCS upon arrival at the emergency room, and had higher AIS-head, ISS, and in-hospital mortality. The patients with skull fracture had 1.7-fold adjusted odds of mortality (95% confidence interval (CI): 1.27–2.25; p

This study aimed to investigate whether changes in the De Ritis ratio (DRR) can be used to stratify the mortality risk of patients with moderate-to-severe traumatic brain injury (TBI). This retrospective study reviewed data for 1347 adult trauma patients (134 deaths and 1213 survival) with moderate-to-severe TBI between 1 January 2009, and 31 December 2020, from the registered trauma database. The outcomes of the patients allocated into the two study groups were compared based on the best Delta DRR (ΔDRR) cutoff point. The first and second DRR of patients who died were significantly higher than those of patients who survived. Elevation of DRR 72–96 h later was found for patients who died, but not for those who survived; the ΔDRR of the patients who died was significantly higher than that of those who survived (1.4 ± 5.8 vs. −0.1 ± 3.3, p = 0.004). Multivariate logistic regression analysis revealed that ΔDRR was a significant independent risk factor for mortality in these patients. Additionally, a ΔDRR of 0.7 was identified as the cutoff value for mortality stratification of adult trauma patients at high risk of mortality with moderate-to-severe TBI.

The De Ritis ratio (DRR), the ratio of serum levels of aspartate aminotransferase/alanine aminotransferase, has been reported to be a valuable biomarker in risk stratification for many liver and non-liver diseases. This study aimed to explore whether the inclusion of DRR at the date of intensive care unit (ICU) admission or days after ICU admission improves the predictive performance of various prognosis prediction models. This study reviewed 888 adult trauma patients (74 deaths and 814 survivors) in the trauma registered database between 1 January 2009, and 31 December 2020. Medical information with AST and ALT levels and derived DRR at the date of ICU admission (1st DRR) and 3–7 day after ICU admission (2nd DRR) was retrieved. Logistic regression was used to build new probability models for mortality prediction using additional DRR variables in various mortality prediction models. There was no significant difference in the 1st DRR between the death and survival patients; however, there was a significantly higher 2nd DRR in the death patients than the survival patients. This study showed that the inclusion of the additional DRR variable, measured 3–7 days after ICU admission, significantly increased the prediction performance in all studied prognosis prediction models.

The De Ritis ratio is widely used to differentiate various causes of liver disease and serves as an independent prognostic predictor for different malignancies and non-malignant illnesses. This retrospective study aimed to identify the association between the De Ritis ratio on admission and mortality outcomes in adult thoracoabdominal trauma patients. A total of 2248 hospitalized adult trauma patients with thoracoabdominal injury, defined as an abbreviated injury scale (AIS) score ≥ 1 in the thoracic and abdominal regions, between 1 January 2009, and 31 December 2019, were included. They were categorized into three tertile groups according to the De Ritis ratio. A 1:1 propensity score-matched study group was established to attenuate the confounding effect of patient characteristics on the mortality outcome assessment. The AST levels of the tertile 1, 2, and 3 groups were 115.8 ± 174.9, 115.7 ± 262.0, and 140.5 ± 209.7 U/L, respectively. Patients in the tertile 3 group had a significantly higher level of AST than those in the tertile 1 group (p = 0.032). In addition, patients in the tertile 1 group had a significantly higher level of ALT than those in the tertile 2 and 3 groups (115.9 ± 158.1 U/L vs. 74.5 ± 107.0 U/L and 61.9 ± 86.0 U/L, p < 0.001). The increased De Ritis ratio in trauma patients with thoracoabdominal injuries was mainly attributed to elevated AST levels. The propensity score-matched patient cohorts revealed that the patients in the tertile 3 group presented a 3.89-fold higher risk of mortality than the patients in the tertile 2 group. In contrast, the patients in the tertile 1 group did not have a significantly different mortality rate than those in the tertile 2 group. This study suggests that a De Ritis ratio > 1.64 may be a useful biomarker to identify patients with a higher risk for mortality.

Abstract Background This study aimed to determine the influence of ageing on the incidence and site of femoral fractures in trauma patients, by taking the sex, body weight, and trauma mechanisms into account. Methods This retrospective study reviewed data from adult trauma patients aged ≥20 years who were admitted into a Level I trauma center, between January 1, 2009 and December 31, 2016. According to the femoral fracture locations, 3859 adult patients with 4011 fracture sites were grouped into five subgroups: proximal type A (n = 1359), proximal type B (n = 1487), proximal type C (n = 59), femoral shaft (n = 640), and distal femur (n = 466) groups. A multivariate logistic regression analysis was applied to identify independent effects of the univariate predictive variables on the occurrence of fracture at a specific site. A two-dimensional plot was presented visually with age and the propensity score accounts for the risk of a fracture at a specific femoral site. Results This analysis revealed that older age was an independent variable that could positively predict the occurrence of proximal type A (OR [95%CI]: 1.03 [1.03–1.04], p

Background. After trauma, the subtypes of white blood cells (WBCs) in circulation and the derived neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) may undergo relative changes and reflect the patients’ immune-inflammatory status and outcome. This retrospective study was designed to investigate the relationship between these variables and the mortality outcomes in adult patients with polytrauma, which is defined as an abbreviated injury scale (AIS) score ≥ 3 in two or more different body regions. Methods. A comparison of the expression of subtypes of WBCs, NLR, MLR, and PLR upon arrival to the emergency department was performed in selected propensity score-matched patient cohorts created from 479 adult patients with polytrauma between 1 January 2015 and 31 December 2019. A multivariate logistic regression analysis was used to identify the independent risk factors for mortality. Results. There were no significant differences in monocyte, neutrophil, and platelet counts, as well as in MLR, NLR, and PLR, between deceased (n = 118) and surviving (n = 361) patients. In the propensity score-matched patient cohorts, which showed no significant differences in sex, age, comorbidities, and injury severity, deceased patients had significantly higher lymphocyte counts than survivors (2214 ± 1372 vs. 1807 ± 1162 [106/L], respectively, p = 0.036). In addition, the multivariate logistic regression analysis revealed that the lymphocyte count (OR, 1.0; 95% confidence interval [CI], 1.00–1.06; p = 0.043) was a significant independent risk factor for mortality in these patients. Conclusions. This study revealed that there was no significant difference in the counts of monocytes, neutrophils, and platelets, as well as in MLR, NLR, and PLR, between deceased and surviving patients with polytrauma. However, a significantly higher lymphocyte count may be associated with a worse mortality.

Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction.

Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration.

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.

Background: White blood cell (WBC) subtypes have been suggested to reflect patients’ immune-inflammatory status. Furthermore, the derived ratio of platelets and WBC subtypes, including monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), is proposed to be associated with patient outcome. Therefore, this study aimed to identify the association of platelets and white blood cells subtypes with the mortality outcome of trauma patients in the intensive care unit (ICU). Method: The medical information from 2854 adult trauma patients admitted to the ICU between 1 January 2009 and 31 December 2019 were retrospectively retrieved from the Trauma Registry System and classified into two groups: the survivors group (n = 2524) and the death group (n = 330). The levels of monocytes, neutrophils, lymphocytes, platelets, and blood-drawn laboratory data detected upon patient arrival to the emergency room and the derived MLR, NLR, and PLR were calculated. Multivariate logistic regression analysis was used to determine the independent effects of univariate predictive variables on mortality occurrence. Result: The results revealed the patients who died had significantly lower platelet counts (175,842 ± 61,713 vs. 206,890 ± 69,006/μL, p < 0.001) but higher levels of lymphocytes (2458 ± 1940 vs. 1971 ± 1453/μL, p < 0.001) than the surviving patients. However, monocyte and neutrophil levels were not significantly different between the death and survivor groups. Moreover, dead patients had a significantly lower PLR than survivors (124.3 ± 110.3 vs. 150.6 ± 106.5, p < 0.001). However, there was no significant difference in MLR or NLR between the dead patients and the survivors. Multivariate logistic regression revealed that male gender, old age, pre-existing hypertension, coronary artery disease and end-stage renal disease, lower Glasgow Coma Scale (GCS), higher Injury Severity Score (ISS), higher level of lymphocytes and lower level of red blood cells and platelets, longer activated partial thromboplastin time (aPTT), and lower level of PLR were independent risk factors associated with higher odds of trauma patient mortality outcome in the ICU. Conclusion: This study revealed that a higher lymphocyte count, lower platelet count, and a lower PLR were associated with higher risk of death in ICU trauma patients.

Abstract Background Transportation by motorcycle and bicycle has become popular in Taiwan, this study was designed to investigate the protective effect of helmet use during motorcycle and bicycle accidents by using a propensity score–matched study based on trauma registry system data. Methods Data of adult patients hospitalized for motorcycle or bicycle accidents between January 1, 2009 and December 31, 2015 were retrieved from the Trauma Registry System. These included 7735 motorcyclists with helmet use, 863 motorcyclists without helmet use, 76 bicyclists with helmet use, and 647 bicyclists without helmet use. The primary outcome measurement was in-hospital mortality. Secondary outcomes were the hospital length of stay (LOS), intensive care unit (ICU) admission rate, and ICU LOS. Normally distributed continuous data were analyzed by the unpaired Student t-test, and non-normally distributed data were compared using the Mann–Whitney U-test. Two-sided Fisher exact or Pearson chi-square tests were used to compare categorical data. Propensity score matching (1:1 ratio using optimal method with a 0.2 caliper width) was performed using NCSS software, adjusting for the following covariates: sex, age, and comorbidities. Further logistic regression was used to evaluate the effect of helmet use on mortality rates of motorcyclists and bicyclists, respectively. Results The mortality rate for motorcyclists with helmet use (1.1%) was significantly lower than for motorcyclists without helmet use (4.2%; odds ratio [OR] 0.2; 95% confidence interval [CI]: 0.17–0.37; p

ObjectiveTo establish the composition of bacteria in mice following cecum ligation and puncture (CLP) through metagenomic analysis and investigate the role of TLRs on the composition of bacteria.MethodsTotal DNA extraction was done from the ascites, blood, and fecal samples from C57BL/6 mice sacrificed at 0, 4, 8, and 16 h, as well as from Tlr2-/-, Tlr4-/-, Tlr5-/-, and NF-κB-/-mice sacrificed at 16 h following CLP. Amplification of the V3-V4 regions of the bacterial 16S rRNA genes by PCR and the Illumina MiSeq sequencer was used for deep sequencing. Hierarchical clustering of the isolates was performed with Ward's method using Euclidean distances. The relative abundance according to operational taxonomic unit (OTU) number or taxa was used to compare the richness among subgroups in the experiments.ResultsThere were 18 taxa that had significantly different abundances among the different samples of the C57BL/6 mice at 16 h following CLP. Various dynamic changes in the infectious bacteria inside the peritoneal cavity after CLP were found. While knockout of Tlr5 and NF-κB impaired the ability of bacterial clearance inside the peritoneal cavity for some kinds of bacteria found in the C57BL/6 mice, the knockout of Tlr4 enhanced clearance for other kinds of bacteria, and they presented excessive abundance in the peritoneal cavity despite their scarce abundance in the stool.ConclusionNF-κB and TLRs are involved in bacterial clearance and in the expression pattern of the bacterial abundance inside the peritoneal cavity during polymicrobial infection.

BackgroundThe shock index (SI) is defined as the ratio of heart rate/systolic blood pressure. This study aimed to determine the performance of delta shock index (ΔSI), a difference between SI upon arrival at the emergency room (ER) and that in the field, in predicting the need for massive transfusion (MT) among adult trauma patients with stable blood pressure.MethodsThis study included registered data from all trauma patients aged 20 years and above who were hospitalized from January 1, 2009 to December 31, 2016. Only patients who were transferred by emergency medical service from the accident site with a systolic blood pressure ≥ 90 mm Hg at the ER were included. The 7,957 enrolled trauma patients were divided into 2 groups, those who had received blood transfusion ≥ 10 U (MT, n = 82) and those who had not (non-MT, n = 7,875). The odds ratios with 95% confidence intervals for the need for MT by a given ΔSI were measured. The plot of specific receiver operating characteristic (ROC) curves was used to evaluate the best cutoff point of ΔSI that could predict the patient's probability of receiving MT.ResultsROC curve analysis showed that a ΔSI of 0.06 as the cutoff point had the highest AUC of 0.61, with a sensitivity of 0.415 and specificity of 0.841. Patients with a ΔSI ≥ 0.00 had a significant 1.8-fold increase in need for MT than those patients with a ΔSI less than 0.00 (1.4% vs. 0.8%, p = 0.01). The larger the ΔSI, the higher the odds of need for an MT. Using the cutoff point of ΔSI of 0.06, patients with a ΔSI ≥ 0.06 had a significant 3.7-fold increase in need for MT than those patients with a ΔSI less than 0.06 (2.7% vs. 0.7%, p < 0.001).ConclusionsThis study indicated that, in trauma patients with stable blood pressure at the ER, the accuracy of prediction of the requirement for MT by ΔSI is low. However, the size of the delta is significantly associated with need for MT and a lack of improvement in the patient's SI at the ER compared to that in the field significantly increases the odds of a need for MT.

Abstract Background The adverse impact of obesity has been extensively studied in the general population; however, the added risk of obesity on trauma-related mortality remains controversial. This study investigated and compared mortality as well injury patterns and length of stay (LOS) in obese and normal-weight patients hospitalized for trauma in the hospital and intensive care unit (ICU) of a Level I trauma center in southern Taiwan. Methods Detailed data of 880 obese adult patients with body mass index (BMI) ≥ 30 kg/m2 and 5391 normal-weight adult patients (25 > BMI ≥ 18.5 kg/m2) who had sustained a trauma injury between January 1, 2009 and December 31, 2013were retrieved from the Trauma Registry System. Pearson’s chi-squared, Fisher’s exact, and independent Student’s t-tests were used to compare differences between groups. Propensity score matching with logistic regression was used to evaluate the effect of obesity on mortality. Results In this study, obese patients were more often men, motorcycle riders and pedestrians, and had a lower proportion of alcohol intoxication compared to normal-weight patients. Analysis of Abbreviated Injury Scale scores revealed that obese trauma patients presented with a higher rate of injury to the thorax, but a lower rate of facial injuries than normal-weight patients. No significant differences were found between obese and normal-weight patients regarding Injury Severity Score (ISS), Trauma-Injury Severity Score (TRISS), mortality, the proportion of patients admitted to the ICU, or LOS in ICU. After propensity score matching, logistic regression of 66 well-matched pairs did not show a significant influence of obesity on mortality (odds ratio: 1.51, 95 % confidence interval: 0.54–4.23 p = 0.438). However, significantly longer hospital LOS (10.6 vs. 9.5 days, respectively, p = 0.044) was observed in obese patients than in normal-weight patients, particularly obese patients with pelvic, tibial, or fibular fractures. Conclusion Compared to normal-weight patients, obese patients presented with different injury characteristics and bodily injury patterns but no difference in mortality.

BACKGROUND:The purpose of this study was to build a model of machine learning (ML) for the prediction of mortality in patients with isolated moderate and severe traumatic brain injury (TBI). METHODS:Hospitalized adult patients registered in the Trauma Registry System between January 2009 and December 2015 were enrolled in this study. Only patients with an Abbreviated Injury Scale (AIS) score ≥ 3 points related to head injuries were included in this study. A total of 1734 (1564 survival and 170 non-survival) and 325 (293 survival and 32 non-survival) patients were included in the training and test sets, respectively. RESULTS:Using demographics and injury characteristics, as well as patient laboratory data, predictive tools (e.g., logistic regression [LR], support vector machine [SVM], decision tree [DT], naive Bayes [NB], and artificial neural networks [ANN]) were used to determine the mortality of individual patients. The predictive performance was evaluated by accuracy, sensitivity, and specificity, as well as by area under the curve (AUC) measures of receiver operator characteristic curves. In the training set, all five ML models had a specificity of more than 90% and all ML models (except the NB) achieved an accuracy of more than 90%. Among them, the ANN had the highest sensitivity (80.59%) in mortality prediction. Regarding performance, the ANN had the highest AUC (0.968), followed by the LR (0.942), SVM (0.935), NB (0.908), and DT (0.872). In the test set, the ANN had the highest sensitivity (84.38%) in mortality prediction, followed by the SVM (65.63%), LR (59.38%), NB (59.38%), and DT (43.75%). CONCLUSIONS:The ANN model provided the best prediction of mortality for patients with isolated moderate and severe TBI.

Background: This study aimed at assessing the effect of a low-fat diet (LFD) in obese mice lacking toll–like receptors (Tlr) and understanding the expression and regulation of microRNAs during weight reduction. Methods: C57BL/6, Tlr5−/−, Tlr2−/− and Tlr4−/− mice were used in this study. A group of mice were fed with a high-fat diet (HFD) (58% kcal) for 12 weeks to induce obesity (diet-induced obesity, DIO). Another group that had been fed with HFD for eight weeks (obese mice) were switched to a low-fat diet (LFD) (10.5% kcal) for the next four weeks to reduce their body weight. The control mice were fed with a standard AIN-76A diet for the entire 12 weeks. The body weight of the mice was measured weekly. At the end of the experiment, epididymal fat weight and adipocyte size were measured. The differentially expressed miRNAs in the fat tissue was determined by next-generation sequencing with real-time quantitative reverse transcription polymerase chain reaction (RT–qPCR). Target prediction and functional annotation of miRNAs were performed using miRSystem database. Results: Switching to LFD significantly reduced the body weight and epididymal fat mass in the HFD-fed C57BL/6 and Tlr5−/− mice but not in Tlr2−/− and Tlr4−/− mice. Weight reduction significantly decreased the size of adipocytes in C57BL/6 but not in the Tlr knockout mice. In Tlr2−/− and Tlr4−/− mice, feeding with HFD and the subsequent weight reduction resulted in an aberrant miRNA expression in the epididymal fat tissue unlike in C57BL/6 and Tlr5−/−. However, target prediction and functional annotation by miRSystem database revealed that all the top 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways of the dysregulated miRNAs during weight reduction in the C57BL/6 mice were also found in the regulated pathways of Tlr5−/−, Tlr2−/−, and Tlr4−/− strains. However, among these pathways, gene sets involved in arginine and proline metabolism and glutathione metabolism were mainly involved in the Tlr knockout mice but not in the C57BL/6 mice. Conclusions: In this study, we demonstrated that feeding of LFD leads to significant body weight reduction in C57BL/6 and Tlr5−/− mice, but not in Tlr2−/− and Tlr4−/− mice. Significant reduction in the size of adipocytes of epididymal fat was only found in C57BL/6, but not in Tlr5−/−, Tlr2−/−, and Tlr4−/− mice. The dysregulated miRNAs in Tlr2−/− and Tlr4−/− mice were different from those in C57BL/6 and Tlr5−/− strains. Among those miRNA-regulated pathways, arginine and proline metabolism as well as glutathione metabolism may have important roles in the Tlr knockout mice rather than in C57BL/6 mice.

Background. This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5−/−), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice. Results. TLR5−/− and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal% high-fat diet (HFD) for 12 weeks; and (3) diet, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal% LFD for 4 weeks. The glucose intolerance in DIO TLR5−/− mice was more significant than that in DIO C57BL/6 mice and was not attenuated by a switch to the LFD. Weight-reduction with LFD had significantly decreased the epididymal fat mass in C57BL/6 mice but not in TLR5−/− mice. In addition, the LFD-fed TLR5−/− mice showed significantly higher expression of ghrelin in the serum and resistin in the epididymal fat than that in C57BL/6 mice. Conclusions. This study demonstrated that TLR5 gene knockout impairs some effects of weight-reduction in DIO.

The levels of circulating microRNAs (miRNAs) in mice with experimental sepsis induced by cecal ligation and puncture (CLP) were determined using whole blood samples obtained from C57BL/6 mice at 4, 8, and 24 h after CLP; miRNA expression analysis was performed in these samples using an miRNA array. Microarray analysis revealed upregulation of 10 miRNA targets (miR-16, miR-17, miR-20a, miR-20b, miR-26a, miR-26b, miR-106a, miR-106b, miR-195, and miR-451). The expression of these miRNA targets in the whole blood, serum, and white blood cells (WBCs) of CLP mice was quantified using quantitative real-time PCR; these values were compared to those in sham-operated C57BL/6 mice, and the results indicated that these miRNA targets were significantly up-regulated in the whole blood and serum but not in the WBCs. In addition, the levels of these 10 miRNA targets in the serum of Tlr2-/-, Tlr4-/-, and NF-κB-/- mice at 8 h after CLP did not decrease significantly., which indicated that the transcription of these miRNAs was not directly mediated by the TLR2/NF-κB or TLR4/NF-κB pathway, and pathways induced by exposure to the gram-positive or gram-negative bacteria. Immunoprecipitation with the Argonaute 2 ribonucleoprotein complex revealed significantly increased expression of the 10 miRNA targets in the serum of mice after CLP, and the levels of 6 (miR-16, miR-17, miR-20a, miR-20b, miR-26a, and miR-26b) of these 10 miRNA targets increased significantly in exosomes isolated using ExoQuick precipitation solution. In this study, we identified circulating miRNAs that were up-regulated after CLP and determined the increase in the levels of these miRNAs, and our results suggest that circulating Ago2 complexes and exosomes may be responsible for the stability of miRNAs in the serum.