Caspase-3 in glioma indicates an unfavorable prognosis by involving surrounding angiogenesis and tumor cell repopulation.

AIM: Effective biomarkers for estimating glioma prognosis are deficient. Canonically, caspase-3 acts as an "apoptosis executioner". However, its prognostic role in glioma and mechanistic effects on prognosis remain unclear. METHODS: With glioma tissue microarrays, the prognostic roles of cleaved caspase-3 and its association with angiogenesis were explored. Next, by analyzing the mRNA microarray data from the CGGA, the prognostic role of CASP3 expression and correlations between CASP3 and markers of glioma angiogenesis and proliferation were investigated. To biologically interpret the prognostic role of caspase-3 in glioma, the influence of caspase-3 on surrounding angiogenesis and glioma cell repopulation was investigated with an in vitro cell co-culture model, which comprises irradiated U87 cells and un-irradiated firefly luciferase (Fluc)-labeled HUVEC (HUVEC-Fluc) or U87 (U87-Fluc) cells. The over-expressed dominant-negative caspase-3 was used to suppress normal caspase-3 activity. RESULTS: High levels of cleaved caspase-3 expression were associated with poor survival outcomes in glioma patients. Higher microvessel density was observed in patients with high levels of cleaved caspase-3 expression. By mining the microarray data in CGGA, it was revealed that higher CASP3 expression was found in glioma patients with lower Karnofsky Performance score, higher WHO grade, malignant histological subtype, wild-type IDH. Higher CASP3 expression indicated a worse survival rate in glioma patients. Patients with high CASP3 expression and negative IDH mutation showed the worst survival rate. Positive correlations were found between CASP3 and markers of tumor angiogenesis and proliferation. Subsequent data based on an in vitro cell co-culture model revealed that caspase-3 in irradiated glioma cells mediated pro-angiogenic and repopulation-promoting effects via regulating COX-2 signaling. With glioma tissue microarrays, high levels of COX-2 expression showed inferior survival outcomes in glioma patients. Glioma patients with high levels of cleaved caspase-3 and COX-2 expression showed the worst survival outcomes. CONCLUSION: This study innovatively identified an unfavorable prognostic role of caspase-3 in glioma. The pro-angiogenic and repopulation-prompting effects of caspase-3/COX-2 signaling may explain its unfavorable prognostic role and offer novel insights into therapy sensitization and curative effect prediction of glioma.

SIRT3 alleviates sepsis-induced acute lung injury by inhibiting pyroptosis via regulating the deacetylation of FoxO3a.

OBJECTIVE: This study mainly analyzes the mechanism of SIRT3 alleviating sepsis-induced acute lung injury (ALI) by regulating the deacetylation of FoxO3a and inhibiting pyroptosis. METHODS: SIRT3-overexpressing and silenced BEAS-2B cells were used to evaluate the effect of SIRT3 on apoptosis in LPS-treated lung epithelial cells. FoxO3a-silenced BEAS-2B cells were also used to verify the mechanism by which SIRT3 inhibited oxidative stress and pyroptosis in vitro in ALI. 3-TYP was used to inhibit the deacetylation function of SIRT3 in vivo. Pyroptosis was assessed by detecting GSDMD-N and LDH efflux. RESULTS: In CLP-induced ALI mice, GSDMD-N and LDH levels were elevated, pyroptosis was induced. Silencing of SIRT3 exacerbated oxidative stress, NLRP3 activation and pyroptosis, and inhibited the deacetylation of FoxO3a. Overexpression of SIRT3 attenuated pyroptosis, induced deacetylation and restored the expression of FoxO3a and MnSOD. Silencing FoxO3a aggravated pyroptosis. Overexpression of SIRT3 restored the reduced FoxO3a expression and suppressed pyroptosis. 3-TYP blocked the promotion of FoxO3a by SIRT3 and the inhibitory effect of SIRT3 on pyroptosis. CONCLUSION: The reduction of SIRT3 in sepsis caused hyperacetylation of FoxO3a, which in turn exacerbates oxidative stress and induces pyroptosis of ALI. Increasing the level of SIRT3 promotes FoxO3a through deacetylation, thereby inhibiting pyroptosis and relieving ALI.

Downregulation of tripartite motif protein 11 attenuates cardiomyocyte apoptosis after ischemia/reperfusion injury via DUSP1-JNK1/2.

Currently, the prevention of ischemic diseases such as myocardial infarction associated with ischemia/reperfusion (I/R) injury remains to be a challenge. Thus, this study was designed to explore the effects of tripartite motif protein 11 (TRIM11) on cardiomyocytes I/R injury and its underlying mechanism. Cardiomyocytes AC16 were used to establish an I/R injury cell model. After TRIM11 downregulation in I/R cells, cell proliferation (0, 12, 24, and 48 h) and apoptosis at 48 h as well as the related molecular changes in oxidative stress-related pathways was detected. Further, after the treatment of TRIM11 overexpression, SP600125, or DUSP1 overexpression, cell proliferation, apoptosis, and related genes were detected again. As per our findings, it was determined that TRIM11 was highly expressed in the cardiomyocytes AC16 after I/R injury. Downregulation of TRIM11 was determined to have significantly reduced I/R-induced proliferation suppression and apoptosis. Besides, I/R-activated c-Jun N-terminal kinase (JNK) signaling and cleaved caspase 3 and Bax expression were significantly inhibited by TRIM11 downregulation. In addition, the overexpression of TRIM11 significantly promoted apoptosis in AC16 cells, and JNK1/2 inhibition and DUSP1 overexpression potently counteracted the induction of TRIM11 overexpression in AC16 cells. These suggested that the downregulation of TRIM11 attenuates apoptosis in AC16 cells after I/R injury probably through the DUSP1-JNK1/2 pathways.

miR-200b suppresses invasiveness and modulates the cytoskeletal and adhesive machinery in esophageal squamous cell carcinoma cells via targeting Kindlin-2.

To further our understanding of the pathobiology of esophageal squamous cell carcinoma (ESCC), we previously performed microRNA profiling that revealed downregulation of miR-200b in ESCC. Using quantitative real-time PCR applied to 88 patient samples, we confirmed that ESCC tumors expressed significantly lower levels of miR-200b compared with the respective adjacent benign tissues (P = 0.003). Importantly, downregulation of miR-200b significantly correlated with shortened survival (P = 0.025), lymph node metastasis (P = 0.002) and advanced clinical stage (P = 0.020) in ESCC patients. Quantitative mass spectrometry identified 57 putative miR-200b targets, including Kindlin-2, previously implicated in the regulation of tumor invasiveness and actin cytoskeleton in other cell types. Enforced expression of miR-200b mimic in ESCC cells led to a decrease of Kindlin-2 expression, whereas transfection of miR-200b inhibitor induced Kindlin-2 expression. Furthermore, transfection of miR-200b mimic or knockdown of Kindlin-2 in ESCC cells decreased cell protrusion and focal adhesion (FA) formation, reduced cell spreading and invasiveness/migration. Enforced expression of Kindlin-2 largely abrogated the inhibitory effects of miR-200b on ESCC cell invasiveness. Mechanistic studies revealed that Rho-family guanosine triphosphatases and FA kinase mediated the biological effects of the miR-200b-Kindlin-2 axis in ESCC cells. To conclude, loss of miR-200b, a frequent biochemical defect in ESCC, correlates with aggressive clinical features. The tumor suppressor effects of miR-200b may be due to its suppression of Kindlin-2, a novel target of miR-200b that modulates actin cytoskeleton, FA formation and the migratory/invasiveness properties of ESCC.

Exogenous Functional Mitochondria Derived from Bone Mesenchymal Stem Cells That Respond to ROS Can Rescue Neural Cells Following Ischemic Stroke.

Background: Upon uptake by stressed cells, functional mitochondria can perform their normal functions, ultimately enhancing the survival of host cells. However, despite the promising results of this approach, there is still a lack of understanding of the specific relationship between nerve cells and functional mitochondria. Methods: Functional mitochondria (F-Mito) were isolated from bone marrow-derived mesenchymal stem cells (BMSCs). The ability of microglia cells to internalize F-Mito was evaluated using a middle cerebral artery occlusion (MCAO) model in C57BL/6J mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model. After OGD/R and F-Mito treatment, the temporal dynamics of intracellular reactive oxygen species (ROS) levels were examined.The relationship between ROS levels and F-Mito uptake was assessed at the individual cell level using MitoSOX, Mitotracker, and HIF-1α labeling. Results: Our findings indicate that microglia cells exhibit enhanced mitochondrial uptake compared to astrocytes. Furthermore, internalized F-Mito reduced ROS levels and HIF-1α levels. Importantly, we found that the ROS response in microglia cells following ischemia is a critical regulator of F-Mito internalization, and promoting autophagy in microglia cells might reduce the uptake of ROS and HIF-1α levels. Conclusion: It is verified that F-Mito derived from BMSCs play a protective role in ischemia-reperfusion injury, as their weakening reduces microglial cell activation and alleviates neuroinflammation.

Dysregulated Long Non-coding RNAs in Myasthenia Gravis- A Mini-Review.

Myasthenia gravis (MG) is an acquired autoimmune disease that is mediated by humoral immunity, supplemented by cellular immunity, along with participation of the complement system. The pathogenesis of MG is complex; although autoimmune dysfunction is clearly implicated, the specific mechanism remains unclear. Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with lengths greater than 200 nucleotides, with increasing evidence of their rich biological functions and high-level structure conservation. LncRNAs can directly interact with proteins and microRNAs to regulate the expression of target genes at the transcription and post-transcription levels. In recent years, emerging studies have suggested that lncRNAs play roles in the differentiation of immune cells, secretion of immune factors, and complement production in the human body. This suggests the involvement of lncRNAs in the occurrence and progression of MG through various mechanisms. In addition, the differentially expressed lncRNAs in peripheral biofluid may be used as a biomarker to diagnose MG and evaluate its prognosis. Moreover, with the development of lncRNA expression regulation technology, it is possible to regulate the differentiation of immune cells and influence the immune response by regulating the expression of lncRNAs, which will provide a potential therapeutic option for MG. Here, we review the research progress on the role of lncRNAs in different pathophysiological events contributing to MG, focusing on specific lncRNAs that may largely contribute to the pathophysiology of MG, which could be used as potential diagnostic biomarkers and therapeutic targets.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16,189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Two substrate-confined sol-gel coassembled ordered macroporous silica structures with an open surface.

A sol-gel cooperative assembly method was demonstrated for the fabrication of inverse opal films with an open surface. In this method, a sol-gel silicate precursor was cooperatively assembled into the interstitial spaces of microspheres at the same time when polystyrene templates formed in between two desired substrates. Silica inverse opals with a three-dimensional ordered macroporous (3DOM) structure were obtained after selective removing the colloidal templates by calcination. The open surfaces with a high degree of interconnected porosity and extremely uniform pore size were characterized by scanning electron microscope (SEM). Optical transmission spectra reveals the existence of considerable deep band gaps of up to 70% and steep band edges of up to 6%/nm in the [111] directions of the 3DOM silica samples. A little shrinkage confirmed by transmission spectra is not larger than 3%, in consistent with the results measured by SEM, which revealing the sufficient and compact infiltration into the interstitial spaces by our confined sol-gel coassembly method. With different incidence angles, the positions of pseudogaps can be easily tuned in the wide range from 720 nm to 887 nm, agreed well with the calculated values by the Bragg law. All the results prove that the sol-gel coassembly method with two substrates confinement is a simple, low cost, convenient and versatile method for the fabrication of silica inverse opals without overlayers in large domains.

Efficacy and safety of a modified intravenous recombinant tissue plasminogen activator regimen in Chinese patients with acute ischemic stroke.

BACKGROUND: Thrombolytic treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA; 0.90 mg/kg, with a maximum dose of 90 mg) has been recommended as the standard management for acute ischemic stroke (AIS) thrombolysis. However, the dose of IV rtPA in Asia remains controversial. METHODS: This study was designed to verify the safety and efficacy of IV rtPA treatment for AIS with a lower dosage (0.90 mg/kg, with a maximum dose of 50 mg). Patients were divided into 3 dosage groups according to body weight (BW): group 1, <55 kg for 0.90 mg/kg; group 2, 55 to 67 kg for 0.75 to 0.90 mg/kg; and group 3, >67 kg for <0.75 mg/kg. The following data were collected: patient demographics, vascular risk factors, neuroimaging results, time of rtPA administration, National Institutes of Health Stroke Scale score before treatment and at 24 hours, and a modified Rankin Scale (mRS) score at 3 months. RESULTS: Eighty-three AIS patients who were of Han Chinese descent were included in the study. The baseline characteristics of the 3 dosage groups were well matched. In group 1 (BW <55 kg for 0.90 mg/kg; n = 19), 57.1% had a favorable outcome at 3 months, compared with 61.2% of patients in group 2 (BW 55-67 kg for 0.75-0.90 mg/kg; n = 33) and 51.5% in group 3 (BW >67 kg for <0.75 mg/kg; n = 31; P = .362). There were no significantly statistical differences in the incidence of symptomatic intracerebral hemorrhage and mortality rate. CONCLUSIONS: This IV rtPA regimen (0.90 mg/kg, with a maximum dose of 50 mg) not only shows sufficient favorable outcome in clinical practice in Chinese patients with AIS but also good health economic savings. This regimen could be suitable for many developing countries.

Linking Leader's Positive Humor and Employee Bootlegging: Empirical Evidence from China.

Purpose: With the increasingly fierce market competitions, non-linear development of organizations through bootlegging has become a key path for enterprises to advance competitiveness. Motivating employees to carry out bootlegging in an organization is becoming an important issue many enterprises face now. This paper aims to analyze the relationship between leader's positive humor and employee bootlegging. We introduced norm violation acceptability as the mediating variable and trust in leader as the moderating variable to propose a theoretical model and verified it by structural equation modeling (SEM) and multiple regression analysis separately. Patients and Methods: Based on both the emotion as social information theory and the social information processing theory, a sample of 278 professional employees working in an information technology (IT) enterprise of China was used to test the moderated mediation model. We used SPSS and AMOS to further verify the research model through structural equation modeling (SEM) and multiple regression analysis. Results: The results indicate that there is a positive relationship between leader's positive humor and employee bootlegging, which is partially mediated by norm violation acceptability. Moreover, trust in leader not only moderated the relationship between leader's positive humor and norm violation acceptability but also strengthened the influence of leader's positive humor on employee bootlegging through norm violation acceptability. Conclusion: These findings have implications in identifying factors which contribute to employee bootlegging and providing a theoretical foundation for leaders in an organization.

A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) is often referred to as "collaterals disease" in traditional Chinese medicine (TCM), and commonly includes ischemic and hemorrhagic CSVD. TCM has a long history of treating CSVD and has demonstrated unique efficacy. Buyang Huanwu Decoction (BHD) is a classical TCM formula that has been used for the prevention and treatment of stroke for hundreds of years. BHD exerts its therapeutic effects on CSVD through a variety of mechanisms. In this review, the clinical and animal studies on BHD and CSVD were systematically introduced. In addition, the pharmacological mechanisms, active components, and clinical applications of BHD in the treatment of CSVD were reviewed. We believe that an in-depth understanding of BHD, its pharmacological mechanism, disease-drug interaction, and other aspects will help in laying the foundation for its development as a new therapeutic strategy for the treatment of CSVD.

Effects of ß-blockers therapy on the 28-day and 3-year survival rates of end-stage renal disease patients with cardiovascular disease: a retrospective cohort study.

Background: ß-blockers have been used in the treatment of end-stage renal disease (ESRD) patients and cardiovascular disease (CVD) patients, separately. However, the effects of ß-blockers on ESRD patients with CVD have not been fully investigated. This study sought to investigate the effects of ß-blockers therapy on the 28-day and 3-year survival rates of ESRD patients with pre-existing CVD who were admitted to the intensive care unit (ICU). Methods: After excluding patients without CVD, receiving a kidney transplant, not admitted to the ICU, and with missing baseline data, this cohort study included 1081 ESRD participants with CVD from the Medical Information Mark for Intensive Care III database. Baseline characteristics, including demographic data and clinical data, were collected. The outcomes were 28-day and 3-year survival rates of the patients. At the 28-day of ICU hospitalization, patients had a mean inpatient hospital stay of 24.7 days. At 3-year, the patients had a median survival time of 489.2 days. Univariate and multivariate Cox regression analyses were used to evaluate the effects of ß-blockers therapy on the 28-day and 3-year survival outcomes of ESRD patients with CVD. Results: The 28-day and 3-year survival rates were 82.8% and 37.9%, respectively. The mean age of the all patients was 68 years, and 642 were male. After adjusting for age, race, hyperlipidemia, dialysis, simplified acute physiological score (SAPS) II, sequential organ failure assessment (SOFA) score, glucocorticoid, hemoglobin, diabetes, hypertension, the 28-day survival rate of the ESRD patients with CVD requiring intensive care who received ß-blockers therapy was higher than that of the patients who did not receive the treatment. Similarly, after adjusting for age, race, hyperlipidemia, dialysis, SAPS II, SOFA score, glucocorticoid, hemoglobin, diabetes, hypertension, creatinine, the long-term survival rate of the patients who received ß-blockers therapy was also higher than that of those who did not. Conclusions: ß-blockers therapy was associated with increased 28-day and 3-year survival rates in ESRD patients with CVD requiring intensive care. Our findings may provide a theoretical basis for the prognostic impact of ß-blockers therapy among patients with ESRD and CVD who were admitted to the ICU.

The impact of outward foreign direct investment on green innovation: the threshold effect of environmental regulation.

Outward foreign direct investment (OFDI) in an open economy has gradually become an important source of green innovation (GI). With the rapid development of China's OFDI, this research studies the impact of OFDI on the country's GI, employing panel data of 30 provinces from 2006 to 2017. We first use the Super-SBM model to measure GI performance and then test the impact of OFDI on GI with the system GMM model. Evidence finds that the negative impact of OFDI on GI is not significant on the whole, but the results of regional regression show that impact of OFDI on GI exhibits obvious regional differences. We then utilize the dynamic threshold panel model to determine the non-linear relationship between OFDI and GI through the perspective of environmental regulation in order to avoid the bias caused by ignoring the impact of institutional factors and time dynamic change. After dividing environmental regulations into command control environmental regulation and market incentive environmental regulation, the research results show that the double threshold effects of both environmental regulations are significant. Command control environmental regulation does not play a role in promoting the effect of OFDI on GI. When the intensity of market incentive environmental regulation is low, OFDI negatively affects GI. Moreover, only when the market incentive regulation shows high intensity can OFDI significantly promote GI. With the continuous growth of China's OFDI, it is therefore necessary to determine the appropriate environmental regulation to improve the reverse spillover effect of OFDI enterprises on the country's GI.

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases.

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single-cell analysis by cytometry by time-of-flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double-negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim3) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA-seq). The heterogeneity among immune cells including CD4+ , CD8+ T cells and NK T cells by single immune cell RNA-seq with significant difference was found by single-cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C-C motif receptor 7 (CCR7) were increased significantly in co-cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.

Modified double lumen tube for a unique bronchial and carinal resection in a patient undergoing uniportal VATS for tumour: A case report.

For bronchial sleeve and carinal resection and reconstruction during uniportal video-assisted thoracic surgery (VATS), ventilation technique remains a demanding challenge for the anesthesiologists. The ventilation techniques require maintaining adequate gas exchange while providing a good surgical exposure. The case we present was a 58-year-old female with carcinoma in the right upper lobe involving the right main bronchus and the lower trachea. Right upper sleeve lobectomy, carinal resection and reconstruction was performed under uniportal VATS. A modified double-lumen tube (DLT) was inserted to achieve one-lung ventilation, and high-frequency jet ventilation (HFJV) was passed through the DLT to provide oxygenation during the anastomosis without interfering with the surgical procedure. The whole procedure was uneventful. We suggest that the double lumen tube could be modified being a simple and safe option for one-lung ventilation in carinal resection and reconstruction under uniportal VATS.

Understanding the Role of Psychological Capital in Humorous Leadership-Employee Creativity Relations.

This paper aims to examine how humorous leadership enhances employee workplace creativity from a novel angle of employee psychological capital (EPC). This study also explores the moderating roles of supervisor-subordinate dyadic tenure and work autonomy in the proposed model. Data from a sample of 355 supervisor-subordinate dyads working in an information technology enterprise in the People's Republic of China was used to test the assumed moderated mediation model. The results indicate the positive relationship between humorous leadership and employee workplace creativity, which is partially mediated by EPC. Moreover, work autonomy significantly moderates the relationship between EPC and employee creativity. Humorous leadership has a significant effect on the extra role behavior of subordinates, leading to workplace creativity. The deliberate establishment of a humorous image by leaders may encourage subordinates to achieve creative goals. Combined with traditional management practices that emphasize the supportive behaviors of leaders, leaders can use humor to provide an open and friendly atmosphere for employees, thereby encouraging creativity in the workplace. Organizations should also place greater emphasis on employee work autonomy, giving employees enough flexibility on when and how they deal with their work; this could enhance the positive impact of other factors on employee workplace creativity. These findings carry implications for research on humorous leadership, EPC, and creativity.

Rapid rule out of acute myocardial infarction in the observe zone using a combination of presentation N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin I.

BACKGROUND AND AIMS: The release of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly triggered by myocardial ischemia. We aimed to investigate whether the addition of NT-proBNP to high-sensitivity cardiac troponin (hs-cTnI) at presentation could provide better performance in risk stratification and thus early rule-out of acute myocardial infarction (AMI) in patients of the "observe zone". METHODS: Emergency department (ED) patients presenting with symptoms suspicious for AMI were consecutively enrolled. Blood samples were obtained at presentation and tested for hs-cTnI and NT-proBNP. All available medical records pertaining to the patient from ED presentation to 30-day follow-up were used for adjudication of the primary outcome. The incremental diagnostic value added by NT-proBNP to hs-cTnI was evaluated by receiver operating characteristic (ROC) analysis, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI). Sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic accuracy of different approaches for early rule out. RESULTS: Of the 165 patients we analyzed, 55 (33.3%) had index AMI. For hs-cTnI alone, area under the curve for index AMI was not significantly increased after adding NT-proBNP (0.773 vs 0.809; p = .076). Adjustment of hs-cTnI by NT-proBNP improved the predictive value of hs-cTnI, showed by cNRI (0.418, 95%CI 0.102-0.735, p = .009) and IDI (0.055, 95%CI 0.017-0.092, p = .004). Compared to hs-cTnI, the combined test identified 14% more patients as low-risk and safe for early discharge. CONCLUSIONS: Combination of presentation hs-cTnI and NT-proBNP provided better predictive performance for AMI in patients of the observe zone presenting with symptoms of chest pain as compared to hs-cTnI alone. The combined test outperformed hs-cTnI by correctly identifying nearly 14% more patients as low-risk and safe for early discharge. Future multi-center studies are needed to verify the results and to determine the best clinical use of the combination of NT-proBNP and hs-cTnI in the early diagnosis of AMI.

miR-21 regulates growth and EMT in lung cancer cells via PTEN/Akt/GSK3ß signaling.

miRNA-21 (miR-21) is overexpressed in various human cancers. Here, we show that miR-21 is overexpressed in human Non-Small Cell Lung Cancer (NSCLC)  and that its up or down-regulation, respectively, increases or decreases cyclin D1 and cyclin E1 expression and coordinately promotes or inhibits proliferation of cancer cells. The perturbations of miR-21 also dramatically reduces or increases epithelial to mesenschymal transition (EMT). We show that regulation of proliferation and EMT are directed by PTEN/Akt/GSK3 beta signaling axis by regulating the expression of invasion markers including E-cadherin, vimentin, snail, slug and beta-catenin. Together, these findings show that miR-21 is a potential target for the development of treatment for NSCLC forms of human lung cancer.

Full laparoscopic incisional hernia repair using a 2-port route technique.

BACKGROUND AND AIMS: The incidence of incisional hernia repair is increasing each year throughout the world. We created a full laparoscopic herniorrhaphy by means of an easy, reliable, and minimally invasive (two trocars) intraperitoneal onlay technique, using different sizes of a DualMesh (W. L. Gore & Associates; Flagstaff, AZ) with the soft side against the adherence material. METHODS: A group of patients with an incisional hernia and other ventral hernias underwent a laparoscopic herniorrhaphy using this technique. By combining simple extra- and endocorporeal manipulation, a mesh, prior to being inserted into peritoneal cavity through a trocar port was completed with four sutures between the corner of the mesh and the abdominal wall, so that when pulling the strands outside the abdomen, the furled intraperitoneal mesh being unfurled flat, was lifted from and overlapped the hernial defect at the top of the abdomen spontaneously and exactly. The mesh was anchored by nonabsorbable surtures and endo-Helical Fasteners. The sutures were either tied and the knots buried subcutaneously, or were eventually removed. RESULTS: It is by employing only two trocars applying this technique to a complete full laparoscopic intraperitoneal onlay of different sizes of a DualMesh incisional and ventral hernia repair. The mesh overlapped all hernial margins nicely and was anchored firmly. Postoperative courses were uneventful, without any complications. During the longest follow-up period of 2 years and 1 month, there was no recurrent evidence of the hernia in this group. CONCLUSIONS: This technique, which applies to almost every laparoscopic ventral hernia repair procedure for use against an adherence mesh, can help to carry out an ideal, easy, and quick orientation and intraperitoneal anchoring of the mesh.

CXCR4 antagonist AMD3100 elicits analgesic effect and restores the GlyRα3 expression against neuropathic pain.

OBJECTIVE: Chemokine CXCL12 and its receptor CXCR4 have been reported to play a critical role in neurogenesis and neuronal differentiation. Recently, some reports have implicated this chemokine signaling in the pathogenesis of many kinds of pain. However, its role in neuropathic pain (NP) is still largely unclear. This study explored the distribution and function of CXCR4 in spinal cord (SC) dorsal horn (DH) in a rat L5 spinal nerve ligation (SNL) model. METHODS: Rats received repeated intrathecal injection of CXCR4 antagonist AMD3100. Behavioral assessments were conducted using a traditional "up-down" method. The spinal CXCL12 contents were measured by enzyme linked immunosorbent assay. The expression and distribution of CXCR4 in the SC were determined by immunoflurescence and Western blot. GlyRα3 expressions were also measured by Western blot or immunofluorescence. RESULTS: SNL induced CXCL12-CXCR4 activation in the spinal DH. Intrathecal administration of AMD3100 alleviated the chronic NP against SNL (P<0.01). CXCR4 was colocalized with GlyRα3-positive neurons in the spinal DH at ratio >97%. Meanwhile, AMD3100 rescued the decrease of GlyRα3 expression (P<0.01 vs the SNL group on Day 14 and Day 21). CONCLUSION: CXCR4 antagonist can elicit analgesic effects and restore the inhibitory neurotransmission such as GlyRα3 against NP.