Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling.

Complex karyotype (CK) is associated with a poor prognosis in both acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB). Transcriptomic analyses have improved our understanding of the disease and risk stratification of myeloid neoplasms; however, CK-specific gene expression signatures have been rarely investigated. In this study, we developed and validated a CK-specific gene expression signature. Differential gene expression analysis between the CK and non-CK groups using data from 348 patients with AML and MDS-EB from four cohorts revealed enrichment of the downregulated genes localized on chromosome 5q or 7q, suggesting that haploinsufficiency due to the deletion of these chromosomes possibly underlies CK pathogenesis. We built a robust transcriptional model for CK prediction using LASSO regression for gene subset selection and validated it using the leave-one-out cross-validation method for fitting the logistic regression model. We established a 10-gene CK signature (CKS) predictive of CK with high predictive accuracy (accuracy 94.22%; AUC 0.977). CKS was significantly associated with shorter overall survival in three independent cohorts, and was comparable to that of previously established risk stratification models for AML. Furthermore, we explored of therapeutic targets among the genes comprising CKS and identified the dysregulated expression of superoxide dismutase 1 (SOD1) gene, which is potentially amenable to SOD1 inhibitors.

Stress Granules Inhibit Coxsackievirus B3-Mediated Cell Death via Reduction of Mitochondrial Reactive Oxygen Species and Viral Extracellular Release.

Stress granules (SGs) are cytoplasmic aggregates of RNA-protein complexes that form in response to various cellular stresses and are known to restrict viral access to host translational machinery. However, the underlying molecular mechanisms of SGs during viral infections require further exploration. In this study, we evaluated the effect of SG formation on cellular responses to coxsackievirus B3 (CVB3) infection. Sodium arsenite (AS)-mediated SG formation suppressed cell death induced by tumor necrosis factor-alpha (TNF-a)/cycloheximide (CHX) treatment in HeLa cells, during which G3BP1, an essential SG component, contributed to the modulation of apoptosis pathways. SG formation in response to AS treatment blocked CVB3-mediated cell death, possibly via the reduction of mitochondrial reactive oxygen species. Furthermore, we examined whether AS treatment would affect small extracellular vesicle (sEV) formation and secretion during CVB3 infection and modulate human monocytic cell (THP-1) response. CVB3-enriched sEVs isolated from HeLa cells were able to infect and replicate THP-1 cells without causing cytotoxicity. Interestingly, sEVs from AS-treated HeLa cells inhibited CVB3 replication in THP-1 cells. These findings suggest that SG formation during CVB3 infection modulates cellular response by inhibiting the release of CVB3-enriched sEVs.

Asterias pectinifera-Derived Collagen Peptides Mixed with Halocynthia roretzi Extracts Exhibit Anti-Photoaging Activities during Exposure to UV Irradiation, and Antibacterial Properties.

Asterias pectinifera, a species of starfish and cause of concern in the aquaculture industry, was recently identified as a source of non-toxic and highly water-soluble collagen peptides. In this study, we investigated the antioxidant and anti-photoaging functions of compounds formulated using collagen peptides from extracts of Asterias pectinifera and Halocynthia roretzi (AH). Our results showed that AH compounds have various skin protective functions, including antioxidant effects, determined by measuring the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl radicals, as well as anti-melanogenic effects, determined by measuring tyrosinase inhibition activity. To determine whether ethosome-encapsulated AH compounds (E(AH)) exert ultraviolet (UV)-protective effects, human dermal fibroblasts or keratinocytes were incubated with E(AH) before and after exposure to UVA or UVB. E(AH) treatment led to inhibition of photoaging-induced secretion of matrix metalloproteinase-1 and interleukin-6 and -8, which are associated with inflammatory responses during UV irradiation. Finally, the antibacterial effects of AH and E(AH) were confirmed against both gram-negative and gram-positive bacteria. Our results indicate that E(AH) has the potential for use in the development of cosmetics with a range of skin protective functions.

Mid-Term Outcomes of Nonoperative Management for Patients with Grade III Blunt Thoracic Aortic Injury.

BACKGROUND: The purpose of our study was to assess the mid-term outcomes of the patients with grade III blunt thoracic aortic injury (BTAI) who were treated non-operatively and to determine the specific conditions for successful NOM. METHODS: We retrospectively reviewed patients with grade III BTAI at a single level 1 trauma center between January 2012 and March 2020, and compared the demographics and outcomes of NOM and thoracic endovascular aortic repair (TEVAR). We also examined the factors contributing to the selection of NOM by calculating the odds ratios for age, sex, initial systolic blood pressure, injury severity score, abbreviated injury scale score, pseudoaneurysm/neck (P/N) ratio, and comorbidity. RESULTS: In total, 46 adults were included. Thirty patients underwent NOM and 19 underwent TEVAR. The time from injury to computed tomography, hospital days, intensive care unit length of stay, and follow-up period showed no difference between the two groups. Aorta-related mortality was not observed in either group. Two patients (7.4%) in the NOM group experienced an increase in pseudoaneurysms: one of them underwent delayed surgical repair without complications, and the other maintained regular follow-up. The odds ratio for selecting NOM was significant when the P/N ratio was < 1.30 (OR = 4.687 [95% CI, 1.229-17.882], p = 0.024). CONCLUSIONS: We suggest that carefully selected patients with BTAI grade III could be observed nonoperatively or treated by delayed intervention on outpatient basis, and a P/N ratio < 1.30 can be used as a cutoff to decide treatment options for BTAI grade III.

Acute right ventricular failure evoked by trauma induced thyroid storm supported by extracorporeal membrane oxygenation: A case report.

RATIONALE: Cardiac arrest due to thyroid storm is a very rare clinical feature with high mortality that presents as multiorgan dysfunction. The mortality rate under this condition is close to 30%, even with appropriate treatment. Most thyroid storms occur in patients with long-standing untreated hyperthyroidism. PATIENT CONCERNS: A 67-year-old woman, who had no specific medical history, was admitted with stupor mentality after a pedestrian traffic accident. DIAGNOSIS: The patient had a Burch and Wartofsky score of 80, well beyond the criteria for diagnosis of a thyroid storm (>45 points). INTERVENTIONS: Venoarterial extracorporeal membrane oxygenation (ECMO) was performed due to persistent unstable vital signs and findings of right ventricular dysfunction after return of spontaneous circulation after cardiopulmonary resuscitation. Circulatory assist with ECMO was performed for 8 days using a beta blocker, steroids, thionamide, and Lugol iodine solution. OUTCOMES: Myocardial function and thyroid hormone levels were rapidly normalized. The patient's mental state recovered, and patient was discharged on day 36 maintaining medication. LESSONS: Diagnosis of a thyroid storm in patients with multiple trauma is very difficult, because most trauma patients have symptoms of tachycardia, altered mental status, and abdominal pain that appear in thyrotoxic events. However, when unexplained shock without bleeding evidence occurs in patients with multiple trauma, a thyroid function test should be performed to rule out thyroid storm. Moreover, if hyperthyroidism is observed in a trauma patient, even if there is no history of hyperthyroidism, the possibility of a thyroid storm must be considered along with medical support treatment such as ECMO in patient with cardiogenic shock.

Structure and antiviral activity of a pectic polysaccharide from the root of Sanguisorba officinalis against enterovirus 71 in vitro/vivo.

The increasing prevalence and pandemic risk of viral diseases warrant the development of safe and effective treatments. In this study, we aimed to elucidate the structure and anti-enterovirus 71 (EV71) effects of polysaccharides isolated from the roots of Sanguisorba officinalis (SO), traditionally used for infectious diseases. The purified polysaccharide (S-a3) was a homogenous macromolecule (260.4 kDa) with a concave and porous surface. Linkage and NMR analyses confirmed that S-a3 is a polysaccharide interlinked with homogalacturonan, rhamnogalacturonan-I, 1,4-α-glucan, and arabinogalactan. S-a3 significantly inhibited cell death and viral gene expression in EV71-infected Vero cells, and alleviated EV71-induced body weight loss, death, and paralysis in the hSCARB2-transgenic mouse model. The effective dose of S-a3 was non-toxic to cells and mice. The antiviral mechanism of S-a3 was associated with the disruption of EV71 attachment to host cells. Our findings demonstrate that polysaccharides from SO can be a safe and effective treatment for EV71 infection.

Changes in the characteristics of trauma patients after the early COVID-19 outbreak: A retrospective study of a regional level 1 trauma center in Republic of Korea.

ABSTRACT: Gyeonggi-do (Gyeonggi province) has the second highest number of coronavirus disease (COVID-19) cases in the Republic of Korea after Seoul, with approximately 25% of the COVID-19 patients as of January 2021. Our center is a level I trauma center located in south Gyeonggi-do, and we aimed to evaluate whether the characteristics of trauma patients changed after the COVID-19 pandemic.We retrospectively reviewed the trauma patients registered with the Korea Trauma Database of the Center from February 2019 to January 2021. The patients were dichotomized into pre-coronavirus disease (pre-COVID) and coronavirus disease (COVID) groups, and their trauma volumes, injury characteristics, intentionality, and outcomes were compared.A total of 2628 and 2636 patients were included in the pre-COVID and COVID groups, respectively. During the COVID-19 period, motorcycle accidents, bicycle accidents, and penetrating injury cases increased, and pedestrian traffic accidents, slips, and injury by machines decreased. The average daily number of patients in the COVID group was lower in March (5.6 ±â€Š2.6/day vs 7.2 ±â€Š2.4/day, P = .014) and higher in September (9.9 ±â€Š3.2/day vs 7.7 ±â€Š2.0/day, P = .003) compared to the pre-COVID group. The COVID group also had a higher ratio of direct admissions (67.5% vs 57.2%, P < .001), proportion of suicidal patients (4.1% vs 2.7%, P = .005), and injury severity scores (14 [9-22] vs 12 [4-22], P < .001) than the pre-COVID group. The overall mortality (4.7% vs 4.9%, P = .670) and intensive care unit length of stay (2 [0-3] days vs 2 [0-4] days, P = .153) was not different between the 2 groups.Although the total number of patients did not change, the COVID-19 pandemic affected the number of monthly admissions and the injury mechanisms changed. More severely injured patients were admitted directly to the trauma center.

Predicting Mortality of Korean Geriatric Trauma Patients: A Comparison between Geriatric Trauma Outcome Score and Trauma and Injury Severity Score.

PURPOSE: The Geriatric Trauma Outcome Score (GTOS) is a new prognostic tool used to predict mortality of geriatric trauma patients. We aimed to apply this model to Korean geriatric trauma patients and compare it with the Trauma and Injury Severity Score (TRISS) method. MATERIALS AND METHODS: Patients aged ≥65 years who were admitted to a level 1 trauma center from 2014 to 2018 were included in this study. Data on age, Injury Severity Score (ISS), packed red blood cell transfusion within 24 h, TRISS, admission disposition, mortality, and discharge disposition were collected. We analyzed the validity of GTOS and TRISS by comparing the area under the survival curve. Subgroup analysis for age, admission disposition, and ISS was performed. RESULTS: Among 2586 participants, the median age was 75 years (interquartile range: 70-81). The median ISS was 9 (interquartile range: 4-12), with a transfusion rate (within 24 h) of 15.9% and mortality rate of 6.1%. The areas under the curve (AUCs) were 0.832 [95% confidence interval (CI), 0.817-0.846] and 0.800 (95% CI, 0.784-0.815) for GTOS and TRISS, respectively. On subgroup analysis, patients with ISS ≥9 showed a higher AUC of GTOS compared to the AUC of TRISS (p<0.05). Other subgroup analyses showed equally good power of discrimination for mortality. CONCLUSION: GTOS can be used to predict mortality of severely injured Korean geriatric patients, and also be helpful in deciding whether invasive or aggressive treatments should be administered to them.

Acute Pulmonary Thromboembolism: 14 Years of Surgical Experience.

BACKGROUND: Pulmonary thromboembolism (PTE) is a life-threatening disease with high mortality. This study aimed to assess the outcomes of surgical embolectomy and to clarify the sustained long-term effects of surgery by comparing preoperative, postoperative, and long-term follow-up echocardiography outcomes. Of 22 survivors, 21 were followed up for a mean (median) period of 6.8±5.4 years (4.2 years). METHODS: We retrospectively reviewed 27 surgical embolectomy cases for massive or submassive acute PTE from 2003 to 2016. Immediate and long-term follow-up outcomes of surgical embolectomy were assessed on the basis of 30-day mortality, long-term mortality, postoperative complications, right ventricular systolic pressure, and tricuspid regurgitation grade. RESULTS: The 30-day and long-term mortality rates were 14.8% (4 of 27) and 4.3% (1 of 23), respectively. Three patients had major postoperative complications, including hypoxic brain damage, acute kidney injury, and endobronchial bleeding, respectively (3.7% each). Right ventricular systolic pressure (median [range], mm Hg) decreased from 62.0 (45.5-78.5) to 31.0 (25.7-37.0, p<0.001). The tricuspid valve regurgitation grade (median [range]) decreased from 1.5 (0.63-2.00) to 0.50 (0.50-1.00, p<0.05). The improvement lasted until the last echocardiographic follow-up. CONCLUSION: Surgical embolectomy revealed favorable mortality and morbidity rates in patients with acute massive or submassive PTE, with sustained long-term improvements in cardiac function.

Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma.

Although increasing evidence indicates that cancers are associated with inflammation, the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in patients with esophageal squamous cell carcinoma remains controversial. We determined the prognostic roles of NLR and PLR in patients with esophageal squamous cell carcinoma who underwent surgical treatment. We retrospectively reviewed 119 patients with esophageal squamous cell carcinoma who underwent surgical resection and complete lymph node dissection from 2004 to 2012. The preoperative NLR and PLR were measured. The patients included 112 (94.1 %) males (mean age, 63.64 ± 8.42 years) of whom 37 (31.1 %) were pathological stage I, 33 (27.7 %) were stage II, and 49 (41.2 %) were stage III. The median follow-up period was 28.68 months. Recurrence was reported in 48 (40.3 %) patients. Mean NLR and PLR were 2.35 ± 1.39 and 140.77 ± 70.47, respectively. A multivariate analysis revealed that NLR was a risk factor for disease-free survival (DFS) (hazard ratio [HR], 1.194; p = 0.031) and overall survival (OS) (HR, 1.230; p = 0.011), whereas PLR was not a risk factor for DFS or OS. The 3-year OS rates were 51.0 % in low-NLR (<2.97) patients and 17.4 % in high-NLR (≥2.97) patients (p = 0.007). Akaike's information criterion decreased when the NLR was included in the multivariate model compared to the multivariate model without NLR. A high NLR was a significant prognostic factor for OS and DFS in patients with surgically treated esophageal squamous cell carcinoma, whereas PLR showed no prognostic significance.

A vector system for ABC transporter-mediated secretion and purification of recombinant proteins in Pseudomonas species.

Pseudomonas fluorescens is an efficient platform for recombinant protein production. P. fluorescens has an ABC transporter secreting endogenous thermostable lipase (TliA) and protease, which can be exploited to transport recombinant proteins across the cell membrane. In this study, the expression vector pDART was constructed by inserting tliDEF, genes encoding the ABC transporter, along with the construct of the lipase ABC transporter recognition domain (LARD), into pDSK519, a widely used shuttle vector. When the gene for the target protein was inserted into the vector, the C-terminally fused LARD allowed it to be secreted through the ABC transporter into the extracellular medium. After secretion of the fused target protein, the LARD containing a hydrophobic C terminus enabled its purification through hydrophobic interaction chromatography (HIC) using a methyl-Sepharose column. Alkaline phosphatase (AP) and green fluorescent protein (GFP) were used to validate the expression, export, and purification of target proteins by the pDART system. Both proteins were secreted into the extracellular medium in P. fluorescens. In particular, AP was secreted in several Pseudomonas species with its enzymatic activity in extracellular media. Furthermore, purification of the target protein using HIC yielded some degree of AP and GFP purification, where AP was purified to almost a single product. The pDART system will provide greater convenience for the secretory production and purification of recombinant proteins in Gram-negative bacteria, such as Pseudomonas species.