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Background. Despite therapeutic advancements, metastasis remains a major cause in breast cancer-specific mortality. Breast cancer cells are susceptible to oxidative damage and exhibit high levels of oxidative stress, including protein damage, DNA damage, and lipid peroxidation. Some breast cancer risk factors may change the level of endogenous oxidative stress. Circulating exosomes play critical roles in tumorigenesis, distant metastasis, and poor prognosis in patients with breast cancer. Methods. We used an online database to analyze the expression and prognostic value of core binding factor subunit β (CBFB) and oxidative stress–related targets in patients with breast cancer. Serum from healthy controls and patients with primary breast cancer or bone metastatic breast cancer in the bone was collected. Exosomes were isolated from the sera or cell culture media. We used an MDA-MB-436-innoculated tumor xenograft mouse model for silencing CBFB. Results. Circulating exosomes from patients with breast cancer metastasis to the bone were rich in CBFB. The human mammary fibroblast cells HMF3A and fibroblasts derived from patient samples cocultured with exosomes had increased α-SMA and vimentin expression and IL-6 and OPN secretion. Similarly, nonmetastatic breast cancer cells cocultured with exosomes exhibited increased levels of certain markers, including vimentin, snail1, CXCR4, and Runx2, and the exosomes had high CBFB expression. Silencing CBFB in metastatic MDA-MB-436 and MDA-MB-157 cells resulted in suppressed migration and invasion and downregulation of vimentin, CXCR4, snail1, Runx2, CD44, and OPN. Conversely, CBFB overexpression resulted in upregulation of Runx2, vimentin, snail1, CD44, and OPN in nonmetastatic T47D and MCF12A cells. The CBFB-rich exosomes derived from MDA-MB-436 cells induced enhanced metastatic phenotypes in the low-metastatic T47D and MCF12A cell lines. Conclusion. Our results revealed that CBFB may promote bone metastasis in patients with breast cancer. Of therapeutic relevance, targeting CBFB resulted in decreased tumor burden and bone metastasis, downregulation of bone metastasis markers, and impaired regulation of oxidative stress–related proteins NAE1 and NOS1.

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Background and objectives Preoxygenation is crucial for providing sufficient oxygen reservoir to a patient before intubation and enables the extension of the period between breathing termination and critical desaturation (safe apnoea time). Conventionally, face mask ventilation is used for preoxygenation. Non-invasive ventilation is a new preoxygenation method. The study objective was to compare the outcomes of non-invasive ventilation and face mask ventilation for preoxygenation. Method PubMed, Embase, Cochrane Library, and the ClinicalTrials.gov registry were searched for eligible studies published from database inception to September 2021. Individual effect sizes were standardized, and a meta-analysis was conducted using random effects models to calculate the pooled effect size. Inclusion criteria were randomised controlled trials of comparing the outcomes of non-invasive ventilation or face mask ventilation for preoxygenation in patients scheduled for surgeries. The primary outcome was safe apnea time, and the secondary outcomes were post-operative complications, number of patients who achieved the expired O2 fraction (FeO2) after 3 min of preoxygenation, minimal SpO2 during tracheal intubation, partial pressure of oxygen in the arterial blood (PaO2) and partial pressure of carbon dioxide (PaCO2) after preoxygenation, and PaO2 and PaCO2 after tracheal intubation. Results 13 trials were eligible for inclusion in this study. Significant differences were observed in safe apnoea time, number of patients who achieved FeO2 90% after preoxygenation for 3 min, and PaO2 and PaCO2 after preoxygenation and tracheal intubation. Only in the non-obese subgroup, no significant difference was observed in safe apnoea time (mean difference: 125.38, 95% confidence interval: − 12.26 to 263.03). Conclusion Non-invasive ventilation appeared to be more effective than conventional methods for preoxygenation. We recommend non-invasive ventilation based on our results.

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combination may represent potential therapeutic approach for patients with advanced HCC.

Background Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue. Methods We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO). Results Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively. Conclusion Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).

Tracheal intubation is an important clinical skill for medical students and junior residents (novice intubators). They are usually trained to use a direct laryngoscope (DL) with straight-to-cuff styletted tracheal tubes first. Only later are they exposed to the bougie as an airway adjunct and videolaryngoscope (VL) with either a standard blade or a hyperangulated blade. The purpose of this study was to investigate the performance of novice intubators in using DL with 3 common stylets.We conducted a prospective study to compare the performance of DL with 3 common stylets, namely the straight-to-cuff stylet (S), hyperangulated VL stylet (G), and bougie (B), on a manikin model.Among 72 participants, no significant difference was observed between the success rates of S, G, and B at the first attempt (84.72%, 81.94%, and 86.11%, respectively [P = .78]) or within 2 minutes (91.67%, 93.06%, and 91.67%, respectively [P = .94]). For participants with successful intubation within 2 minutes, the average total intubation times for S, G, and B were 25.05, 24.39, and 37.45 seconds, respectively. Among the 3 stylets, B had the longest intubation time, which differed significantly from S and G (P .01).The performances of novice intubators with 3 different stylets were similar. The success rates for DL with either hyperangulated VL stylet or bougie were not inferior compared with the straight-to-cuff stylet on manikin airway training model. If we properly trained novice intubators to use corresponding maneuvers, they can learn to use the 3 stylets early in their airway learning course.

Simple Summary Hepatitis virus is a major risk factor for liver cancer. We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. The combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically sup-presses the proliferation of vHCC cells and effectively reduces the tumor burden. Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC. Abstract Background: Hepatitis virus is a major risk factor for liver cancer. The mitochondrial dysfunction IFN gamma-related pathways are activated after virus infection. Jak family-related protein is involved in the downstream of IFN gamma-related pathways. However, the effect of the IFNGR-JAK-STAT pathway acting as functional regulators of their related protein expression on virus infection and hepatocellular carcinoma (HCC) remains unclear. Interestingly, the role of the DNA repair gene (PARP1) in therapy resistant cancers also has not been studied and explored well. In this study, we hypothesized that momelotinib could suppress the progression of HCC by targeting Jak family related and PARP1 DNA repair protein. Based on this observation, we link the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors. Methods: We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation assay, cell invasion, migration, and tumorsphere-formation assay were used for drug cytotoxicity, cell viability, and possible molecular mechanism. Result: We first demonstrated that the expression of Jak1 and 2 is significantly upregulated in vHCC than in nvHCC/normal liver tissues. In addition, the gene expression of IFN gamma-related pathways is activated after virus infection. Additionally, we found that momelotinib significantly inhibited the growth of HCC cells and reduces the expression of Jak2, which showed the importance of momelotinib in targeting Jak2 and reducing tumorigenesis in HCC. Meanwhile, momelotinib effectively inhibited the IFNGR-JAK-STAT pathway and reduced the migratory/invasive ability of vHCC cells through down-regulating EMT biomarkers (E-cadherin and vimentin), transcription factor (Slug), and significantly inhibits the DNA damage repair enzyme PARP1. It also induced cell apoptosis of vHCC cells. Furthermore, the combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden. Conclusions: Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.

Traumatic brain injury (TBI) causes major socioeconomic problems worldwide. In the United States, nearly three-quarters of patients with TBI have mild TBI (mTBI). 32% of these patients may develop dizziness. In this study, we analyzed the factor structure of the traditional Chinese version of the DHI and evaluate the differences in DHI factors between dizziness and nondizziness groups. In total, 315 patients with mTBI, comprising 158 with self-reported dizziness and 157 without dizziness, were recruited from three hospitals. The responses for Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI) demonstrated between-group differences. The Chinese DHI had internal validity and had four factors that differed from the English version (3 aspects). The group effects for the physical subscale remained significantly different even after adjustments in the propensity score model. For the Chinese version, two of four factors remained significantly different in the effects between self-reported dizziness and nondizziness groups. The factors of our Chinese DHI differed from those of the original English version of DHI. After adjustments using the propensity score model, the physical subscale demonstrated significant differences between the self-reported dizziness and nondizziness groups. Only two factors from our Chinese DHI were significantly different; moreover, it contained only three physical, five functional, and three emotional items.

The authors have requested that this preprint be removed from Research Square.

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA&minus, LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with &lsquo, normal&rsquo, paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

Rationale: Postpartum ovarian vein thrombophlebitis (POVT) is a rare condition, and it can lead to severe complications and mortality. Here we report a patient who presented with vaginal bleeding and the diagnosis of POVT was confirmed by imaging. Patient concerns: A 38-year-old postpartum woman without remarkable medical history presented with vaginal bleeding and lower abdominal pain. Diagnoses: The diagnosis was confirmed by computed tomography scan marked by a thrombus mass involving the right ovarian vein and inferior vena cava. Interventions: The patient was treated with intravenous antibiotics and low-molecular-weight heparin. Outcomes: The patient recovered smoothly without complications. Lessons: We should pay high attention to the recognition and management of POVT to prevent morbidity and mortality.

Background Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 −) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2− breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells. Methods We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment. Results High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4. Conclusion The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells.

Resistance to radiotherapy (IR), with consequent disease recurrence, continues to limit the efficacy of contemporary anticancer treatment for patients with hepatocellular carcinoma (HCC), especially in late stage. Despite accruing evidence implicating the PI3K/AKT signaling pathway in cancer-promoting hypoxia, cancerous cell proliferation and radiotherapy-resistance, it remains unclear which molecular constituent of the pathway facilitates adaptation of aggressive HCC cells to tumoral stress signals and drives their evasion of repeated IR-toxicity. This present study investigated the role of PDK1 signaling in IR-resistance, enhanced DNA damage repair and post-IR relapse, characteristic of aggressive HCC cells, while exploring potential PDK1-targetability to improve radiosensitivity. The study employed bioinformatics analyses of gene expression profile and functional protein&ndash, protein interaction, generation of IR-resistant clones, flow cytometry-based ALDH activity and side-population (SP) characterization, siRNA-mediated loss-of-PDK1function, western-blotting, immunohistochemistry and functional assays including cell viability, migration, invasion, clonogenicity and tumorsphere formation assays. We showed that the aberrantly expressed PDK1 characterizes poorly differentiated HCC CVCL_7955, Mahlavu, SK-HEP1 and Hep3B cells, compared to the well-differentiated Huh7 or normal adult liver epithelial THLE-2 cells, and independently activates the PI3K/AKT/mTOR signaling. Molecular ablation of PDK1 function enhanced susceptibility of HCC cells to IR and was associated with deactivated PI3K/AKT/mTOR signaling. Additionally, PDK1-driven IR-resistance positively correlated with activated PI3K signaling, enhanced HCC cell motility and invasiveness, augmented EMT, upregulated stemness markers ALDH1A1, PROM1, SOX2, KLF4 and POU5F1, increased tumorsphere-formation efficiency and suppressed biomarkers of DNA damage&mdash, RAD50, MSH3, MLH3 and ERCC2. Furthermore, the acquired IR-resistant phenotype of Huh7 cells was strongly associated with significantly increased ALDH activity, SP-enrichment, and direct ALDH1-PDK1 interaction. Moreover, BX795-mediated pharmacological inhibition of PDK1 synergistically enhances the radiosensitivity of erstwhile resistant cells, increased Bax/Bcl-2 apoptotic ratio, while suppressing oncogenicity and clonogenicity. We provide preclinical evidence implicating PDK1 as an active driver of IR-resistance by activation of the PI3K/AKT/mTOR signaling, up-modulation of cancer stemness signaling and suppression of DNA damage, thus, projecting PDK1-targeting as a putative enhancer of radiosensitivity and a potential new therapeutic approach for patients with IR-resistant HCC.

Background Falls represent a global health issue among older adults and cause a considerable burden on medical systems. In this study, a fall-risk assessment profile was developed for community-dwelling older adults. Method The data of survey participants aged > 65 years were obtained from three rounds (2005, 2009, and 2013) of the National Health Interview Survey in Taiwan. In total, 8356 older participants were included in this study. Logistic regression analyses were used to determine potential predictors associated with falls. The regression coefficients of the predictors in the final model were translated into scores (by multiplying by 5) and then summed to obtain a total risk-score for falls. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative performance of the risk assessment profile. Result Self-reported falls within 1 year accounted for 19.1% of the total falls. The predictors that were included in the risk profile according to the logistic regression analysis results were as follows: female sex (adjusted odds ratio = 1.57; risk-score = 2), living alone (adjusted odds ratio = 1.56; risk-score = 2), urinary incontinence (adjusted odds ratio = 1.36; risk-score = 2), perceived unhealthiness (adjusted odds ratio = 1.32; risk-score = 1), perceived pain (adjusted odds ratio = 1.51; risk-score = 2), hospital admission in the past year (adjusted odds ratio = 2.42; risk-score = 4), low activity of daily living (ADL) scores (adjusted odds ratio = 1.29; risk-score = 1), and low mobility function scores (adjusted odds ratio = 1.68; risk-score = 3). At a total risk-score cutoff point of 6 (range 0–17), the model predicted falls with a sensitivity and specificity of 75.16 and 52.75%, respectively (area under the ROC curve = 0.70). Conclusion The fall-risk assessment profile comprising eight predictors—female sex, living alone, incontinence, perceived unhealthiness, perceived pain, hospital admission in the past year, low ADL scores, and low mobility function scores—may serve as an assessment tool for identification of older adults with a high risk of falling, and assessment results can be used to facilitate community-based intervention.

Background Emergency intubation in a patient with advanced ankylosing spondylitis (AS) who presents with severe thoracic kyphosis deformity, rigid cervical flexion deformity of the neck, and an inability to achieve the supine position is particularly challenging to emergency physicians. Case Report This study reports on an AS patient presenting with these difficult airway characteristics and acute respiratory failure who was successfully intubated using video laryngoscope-assisted inverse intubation (II) and blind digital intubation (BDI). By using Pentax AirwayScope-assisted inverse intubation, the tracheal tube tip was passed through the glottic opening, but an unexpected resistance occurred during tube advancement, which was overcome by subsequent BDI. By using laryngoscope-assisted II complemented by the BDI technique, the patient was successfully intubated without complications. Why Should an Emergency Physician Be Aware of This? Our case demonstrated that these two emergency airway management techniques are valuable backup methods and complement each other when applied to certain unstable airways, especially when the traditional patient position is not easily accomplished. Unexpected difficulty is not rare during airway management; emergency physicians should always be well prepared both mentally and practically.

Introduction. Unintentional injury remains the leading cause of death in children worldwide. Adequate parental supervision is a crucial strategy for preventing injury. Many factors, such as a large family size, poor socioeconomic status, and the caregiver being a single mother, contribute to unintentional injury in children. In addition, sleep deprivation in caregivers might be associated with injury in children because sleep deprivation causes impaired daytime cognitive function, wake-state instability, and negative moods, thereby impairing caregiver supervision. Therefore, this study determines the association between injury in children and the sleep quality of their primary caregivers. Method. This is a retrospective case–control study on unintentional injury in children aged 0 to 4 years who visited the emergency department (case group) and an age- and sex-matched control group. Sleep quality in caregivers was assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to evaluate the association between aspects of the PSQI and injury. A propensity score model was used to generate a quasirandomized design. Results. This case-control study recruiting 277 injured and 274 noninjured children was conducted in Taiwan. There was no statistically significant difference in child’s age and primary caregiver’s age between the injured and noninjured groups. The primary outcome, Pittsburgh sleep quality index, was not significantly different between the two groups. The average scores of sleep duration and habitual sleep efficiency in the control group were higher than those in the case group. However, there was no difference between the two groups after adjusting via a propensity score model, including the following potential confounders, child’s age, child’s sex, number of previous injury, caregiver mental status, caregiver’s sex and caregiver’s age, and the number of children living together. Conclusion. Our study was the first to examine the association between injury in children and the sleep quality of their primary caregivers. We observed that no PSQI component significantly affected the risk of injury among children.

Background: With recorded under-performance of current standard therapeutic strategies as highlighted by high rates of post-treatment (resection or local ablation) recurrence, resistance to chemotherapy, poor overall survival, and an increasing global incidence, hepatocellular carcinoma (HCC) constitutes a medical challenge. Accumulating evidence implicates the presence of HCC stem cells (HCC-SCs) in HCC development, drug-resistance, recurrence, and progression. Therefore, treatment strategies targeting both HCC-SCs and non-CSCs are essential. Methods: Recently, there has been an increasing suggestion of MALAT1 oncogenic activity in HCC, however, its role in HCC stemness remains unexplored. Herein, we investigated the probable role of MALAT1 in the SCs-like phenotype of HCC and explored likely molecular mechanisms by which MALAT1 modulates HCC-SCs-like and metastatic phenotypes. Results: We showed that relative to normal, cirrhotic, or dysplastic liver conditions, MALAT1 was aberrantly expressed in HCC, similar to its overexpression in Huh7, Mahlavu, and SK-Hep1 HCC cells lines, compared to the normal liver cell line THLE-2. We also demonstrated a positive correlation between MALAT1 expression and poor cell differentiation status in HCC using RNAscope. Interestingly, we demonstrated that shRNA-mediated silencing of MALAT1 concomitantly downregulated the expression levels of &beta, catenin, Stat3, c-Myc, CK19, vimentin, and Twist1 proteins, inhibited HCC oncogenicity, and significantly suppressed the HCC-SCs-related dye-effluxing potential of HCC cells and reduced their ALDH-1 activity, partially due to inhibited MALAT1-&beta, catenin interaction. Additionally, using TOP/FOP (TCL/LEF-Firefly luciferase) Flash, RT-PCR, and western blot assays, we showed that silencing MALAT1 downregulates &beta, catenin expression, dysregulates the canonical Wnt signaling pathway, and consequently attenuates HCC tumorsphere formation efficiency, with concurrent reduction in CD133+ and CD90+ HCC cell population, and inhibits tumor growth in SK-Hep1-bearing mice. Conclusions: Taken together, our data indicate that MALAT1/Wnt is a targetable molecular candidate, and the therapeutic targeting of MALAT1/Wnt may constitute a novel promising anticancer strategy for HCC treatment.

This study demonstrated a training program of the suction-assisted laryngoscopy assisted decontamination (S.A.L.A.D.) technique for emergency medical technician paramedic (EMT-P). The effectiveness of the training program on the improvements of skills and confidence in managing soiled airway was evaluated.In this pilot before-after study, 41 EMT-P participated in a training program which consisted of 1 training course and 3 evaluation scenarios. The training course included lectures, demonstration, and practice and focused on how to perform endotracheal intubation in soiled airway with the S.A.L.A.D technique. The first scenario was performed on standard airway mannequin head with clean airway (control scenario). The second scenario (pre-training scenario) and the third scenario (post-training scenario) were performed in airway with simulated massive vomiting. The post-training scenario was applied immediately after the training course. All trainees were requested to perform endotracheal intubation for 3 times in each scenario. The "pass" of a scenario was defined as more than twice successful intubation in a scenario. The intubation time, count of successful intubation, pass rate, and the confidence in endotracheal intubation were evaluated.The intubation time in the post-training scenario was significantly shorter than that in the pre-training scenario (P = .031). The pass rate of the control, pre-training, and post-training scenario was 100%, 82.9%, and 92.7%, respectively. The proportion of trainees reporting confident or very confident in endotracheal intubation in soiled airway increased from 22.0% to 97.6% after the training program. Kaplan-Meier analysis revealed that the adjusted hazard ratio of successful intubation for post-training versus pre-training scenario was 2.13 (95% confidence interval of 1.57-2.91).The S.A.L.A.D. technique training could efficiently help EMT-P performing endotracheal intubation during massive vomiting simulation.

Silibinin is a flavonoid with antihepatotoxic properties and pleiotropic anticancer capabilities. This study investigated silibinin inhibition of cell invasion by down-regulating matrix metalloproteinase-2 (MMP-2) expression, via attenuation of activator protein-1 (AP-1) in IL-6-stimulated LoVo colon cancer cells. Western blot data showed that the expression of MMP-2 protein was reduced 1.6- or 1.7-fold over the control by treatment with silibinin or JNK inhibitor in the models. Similar results were revealed in zymography and confocal microscopy. Pretreatment with silibinin also abolished the binding activity of AP-1 and MMP-2 promoter activity via AP-1 binding, as observed by EMSA and luciferase assay. Finally, a [(3)H]-thymidine incorporation proliferation assay and cell migration assay demonstrated that silibinin inhibited IL-6-stimulated LoVo cell proliferation and invasion. Taken together, these data indicated that silibinin inhibits LoVo cell invasion with the reduction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel antimetastatic application for silibinin in colon cancer chemoprevention.

Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs commonly in cancer cells and endothelial cells, and contributes to angiogenesis. Wogonin is a compound with many biologically relevant properties. We previously reported that wogonin blocked IL-6-induced angiogenesis through suppression of VEGF expression, an important regulator of angiogenesis. However, the pathway involved in the suppressive effect of wogonin on IL-6-induced VEGF has not been completely clarified. This study aimed to investigate the molecular mechanisms participating in the suppression of wogonin on IL-6-induced VEGF in vitro, focusing on IL-6R/JAK1/STAT3/VEGF pathway. Both STAT3 siRNA and wogonin treatment resulted in an abolition of the expression of VEGF. Moreover, our data revealed that wogonin treatment after STAT3 knock-down did not further suppress VEGF expression. The addition of IL-6R siRNA or wogonin resulted in a decrease in the expression level of the phosphorylated JAK1 protein. Furthermore, wogonin significantly decreased the amount of phosphorylated STAT3. Finally, by EMSA, wogonin suppressed IL-6-induced STAT3 binding activity in a concentration-dependent manner. Taken together, our results show that wogonin suppresses IL-6-induced VEGF by modulating the IL-6R/JAK1/STAT3 signaling pathway. Based on this study, we suggest that wogonin may provide a new potential therapeutic option for treatment of IL-6-related pathological angiogenesis.

Objectives: The aim of the present study was to evaluate the performance of three indirect laryngoscopes, Truview EVO2 laryngoscope, Clarus Levitan fiberoptic stylet and AirwayScope AWS, in comparison with direct Macintosh laryngoscope (ML) when performed in normal and difficult airway scenarios. Methods: This prospective comparative study recruited 30 emergency physicians familiar with direct laryngoscopic intubation. Intubations were performed on manikin and were repeated twice for both scenarios. The primary end points were intubation time and rate of failed intubation. Glottis visualization was graded on Cormack and Lehane score and VAS. Results: In normal airway scenario: AWS had shortest intubation time (6.0 s) followed by ML (8.7 s); VAS score of ML and AWS was lower (easier to use) than the other two devices; Cormack and Lehane score was similar for all devices. In difficult airway scenario: AWS had shortest intubation time (5.9 s); VAS score of AWS was lower than the other three devices; TVL, FOS, AWS had better Cormack and Lehane score than ML. Intubation time, rate of failed intubation, and Cormack and Lehane score were similar between attempts in both scenarios. Learning effect was significant in FOS in both scenarios and in TVL in normal airway scenario. Conclusions: AWS performed best in normal and difficult airways. ML performed better than TVL and FOS in normal airways. Performances of ML, TVL and FOS were similar in difficult airways. Skills with AWS could be mastered rapidly. TVL and FOS required more practice to gain expertise.

Background Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning. Methods We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning. Results Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR] = 0.83, 95% CI = 0.38-1.80), memory impairment (18.2% vs 23.8%, RR = 0.80, 95% CI = 0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI = 0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59-1.39). Two sessions of HBO treatment exhibited no advantage over one session. Conclusions The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.

Numerous studies suggest that in asymptomatic patients, routine follow-up CT is not indicated due to the insignificant findings found on these patients. A 53-year-old man, who denied any underlying disease before, underwent colonoscopy for routine health examination. Sudden onset of abdominal pain around left upper quarter was mentioned at our emergency department. Grade II spleen laceration was found on CT scan. Splenic injury was found few hours later on the day of colonoscopy. It might result from the extra tension between the spleen and splenic flexure which varies from different positions of patients.

Fever and headache are common problems encountered by emergency physicians. The diagnostic etiologies can range from benign conditions to life-threatening conditions. Subarachnoid hemorrhage from a ruptured intracranial aneurysm that was caused by an Aspergillus infection is a rare event with a high mortality rate. The central nervous system (CNS) Aspergillus infection should be considered as a differential diagnosis when an immunocompromised patient presents with fever and headache. We reported a 61-year-old male with the above presentations collapsed unexpectedly shortly after been seen by emergency physicians without any imminent signs. He was eventually diagnosed as having an Aspergillus infection of the central nervous system. The clinical manifestations of intracranial Aspergillus infection are subtle and highly variable in term of severity, onset and progression. Early detection is often difficult and even aggressive treatment often results in a drastic medical outcome, which has legal implications for the treating physicians. This case typifies the high stakes associated with the diagnostic challenges that are encountered by emergency physicians when evaluating immunocompromised patients who are experiencing flu-like symptoms.

Leptin contributes to the pathogenesis of vascular repair and cardiovascular events. This study evaluated the molecular mechanism of EGCG in balloon injury-induced leptin expression. According to immunohistochemical and confocal analyses, leptin expression was increased and the aortic lumen exhibited narrowing after balloon injury. EGCG treatment attenuated leptin expression and diminished neointimal formation. The in vitro study showed that angiotensin II (Ang II) induced the migration and proliferation of cultured vascular smooth muscle cells (VSMCs), whereas treatment with EGCG, leptin siRNA, and c-Jun siRNA inhibited the migration and proliferation of VSMCs significantly. The EMSA shows that balloon injury increased AP-1-binding activity, and EGCG and c-Jun siRNA inhibited the AP-1-binding activity. Western blot and real-time RT-PCR analyses revealed similar results in intimal tissue samples. In summary, balloon injury induces leptin expression in the carotid artery of rats, and EGCG inhibits leptin expression through the JNK/AP-1 pathway and also attenuates neointimal formation.

The aim of the present study was to evaluate the performance of three indirect laryngoscopes, Truview EVO2 laryngoscope, Clarus Levitan fiberoptic stylet and AirwayScope AWS, in comparison with direct Macintosh laryngoscope (ML) when performed in normal and difficult airway scenarios.This prospective comparative study recruited 30 emergency physicians familiar with direct laryngoscopic intubation. Intubations were performed on manikin and were repeated twice for both scenarios. The primary end points were intubation time and rate of failed intubation. Glottis visualization was graded on Cormack and Lehane score and VAS.In normal airway scenario: AWS had shortest intubation time (6.0 s) followed by ML (8.7 s); VAS score of ML and AWS was lower (easier to use) than the other two devices; Cormack and Lehane score was similar for all devices. In difficult airway scenario: AWS had shortest intubation time (5.9 s); VAS score of AWS was lower than the other three devices; TVL, FOS, AWS had better Cormack and Lehane score than ML. Intubation time, rate of failed intubation, and Cormack and Lehane score were similar between attempts in both scenarios. Learning effect was significant in FOS in both scenarios and in TVL in normal airway scenario.AWS performed best in normal and difficult airways. ML performed better than TVL and FOS in normal airways. Performances of ML, TVL and FOS were similar in difficult airways. Skills with AWS could be mastered rapidly. TVL and FOS required more practice to gain expertise.

Abdominal abscess resulting from a perforated diverticulitis has never been reported as a cause of acute urinary retention. Our patient is the first case to be reported. Because of the atypical presentation, he was initially misdiagnosed and treated as having acute prostatitis. Emergency physicians should have a high index of suspicion. Detailed history, abdominal sonography, and digital examination are helpful in diagnosing this disease.