One-lung Ventilation for Patients With Laryngo-tracheal Stenosis: A Case Report and Literature Review.

Context: Laryngo-tracheal stenosis (LTS) is a relatively rare disease, and conventional methods have difficulty achieving one-lung ventilation (OLV) when an anatomical abnormality exists. Selecting an appropriate method for patients with LTS can ensure oxygenation, collapse the lung, and reduce damage. Objective: The study intended to perform a comprehensive review of the literature and a systematic review to examine the characteristics and management of OLV for LTS patients. Design: The research team performed a narrative review by searching the PubMed and China National Knowledge Infrastructure (CNKI) databases. The search used the keywords one-lung ventilation and tracheal stenosis. The team then performed a review, including the studies found in the search and the research team's own case study. Setting: The study took place at the First Hospital of Jilin University in Changchun, Jilin, China. Participant: The participant in the current case study was a 72-year-old, female patient with generalized tracheal narrowing. Results: Nine participants achieved OLV through BB, with the anesthesiologist performing SLT and using extraluminal BB for six participants. Conclusions: Several methods can successfully achieve OLV for patients with difficult airways, but the current research team found that a small, single-lumen tube (SLT) and extraluminal bronchial blocker (BB) may be a better choice for patients with tracheal stenosis.

Current and emerging molecular and epigenetic disease entities in acute myeloid leukemia and a critical assessment of their therapeutic modalities.

Acute myeloid leukemia (AML) is the most frequently diagnosed acute leukemia, and its incidence increases with age. Although the etiology of AML remains unknown, exposure to genotoxic agents or some prior hematologic disorders could lead to the development of this condition. The pathogenesis of AML involves the development of malignant transformation of hematopoietic stem cells that undergo successive genomic alterations, ultimately giving rise to a full-blown disease. From the disease biology perspective, AML is considered to be extremely complex with significant genetic, epigenetic, and phenotypic variations. Molecular and cytogenetic alterations in AML include mutations in those subsets of genes that are involved in normal cell proliferation, maturation and survival, thus posing significant challenge to targeting these pathways without attendant toxicity. In addition, multiple malignant cells co-exist in the majority of AML patients. Individual subclones are characterized by unique genetic and epigenetic abnormalities, which contribute to the differences in their response to treatment. As a result, despite a dramatic progress in our understanding of the pathobiology of AML, not much has changed in therapeutic approaches to treat AML in the past four decades. Dose and regimen modifications with improved supportive care have contributed to improved outcomes by reducing toxicity-related side effects. Several drug candidates are currently being developed, including targeted small-molecule inhibitors, cytotoxic chemotherapies, monoclonal antibodies and epigenetic drugs. This review summarizes the current state of affairs in the pathobiological and therapeutic aspects of AML.

A review on the physiological and pathophysiological role of endothelial glycocalyx.

The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It comprises of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and adherent plasma proteins. The glycocalyx maintains homeostasis of the vasculature, which includes controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and regulating leukocyte adhesion. In the past decades, the number of studies on endothelial glycocalyx has steadily grown. Glycocalyx emerged as an essential part of blood vessels involved in multiple physiological functions. Damage to glycocalyx is associated with many types of diseases. The structure and physiology and pathophysiology of the glycocalyx, as well as the clinical effects of glycocalyx degradation, are addressed throughout this study. We strive in particular to define therapeutic approaches for the survival or reparation of the glycocalyx.

[Experimental study on anti-tumor effect and mechanism of green tea extract].

OBJECTIVE: To explore anti-cancer effect and mechanism of green tea extract (GTE) in three human oral squamous carcinoma cell lines (CAL-27, SCC-25 and KB). METHODS: The cell lines were in vitro cultured and its growth inhibition was detected by MTT. After screening most sensitive cell line, effect of GTE on CAL-27 cell cycle was analyzed by flow cytometry. The protein expression of GTE on CAL-27 cell strain was determined by protein chip technique. The protein expression of CDK4, CDK6, and p-PDK1 was verified by using Western blot. RESULTS: Compared with the control group, the inhibition rate on CAL-27 increased significantly after treated by 50, 100, 200, and 400 µg/mL GTE; the inhibition rate on KB increased after treated by 100, 200, and 400 µg/mL GTE; the inhibition rate on SCC-25 increased after treated by 25, 50, 100, 200, and 400 µg/mL GTE, all with statistical difference and in dose dependant manner (P < 0.01). Flow cytometric analysis showed that, when compared with the control group, 50 µg/mL GTE arrested CAL-27 cells in the G2/M phase (P < 0.05), and 100 µg/mL GTE arrested CAL-27 cells in the G2/M phase with concurrent decreased cells in the G0/G1 phase (P < 0.01). Totally 107 proteins were analyzed by protein chip technique. After treated by GTE, a total of 13 proteins significantly changed in CAL-27 cell line. Western blot showed that 25, 50, and 100 µg/mL GTE inhibited the expression of phopho-phosphoinositide-dependent protein kinase 1 (p-PDK1), cyclin-dependent kinase 4 (CDK4), and CDK6 of CAL-27 cell line with statistical difference (P < 0.05). The higher the drug concentration, the higher the inhibition rate (P < 0.05). CONCLUSIONS: GTE could inhibit the proliferation of different human oral squamous carcinoma cell lines. CAL-27 is a sensitive cell line. GTE significantly affected EGFR and Notch signal network, and influenced changes of cell cycle related protein expression levels through the aforesaid channels, resulting in cell cycle arrest in S and G2/M phases.

[Retracted] MicroRNA­491­5p suppresses cervical cancer cell growth by targeting hTERT.

Following the publication of this paper, an interested reader drew to the attention of the Office that the GAPDH control bands shown in Fig. 5 were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors independently contacted the Editorial Office requesting that the paper be retracted. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 34: 979­986, 2015; DOI: 10.3892/or.2015.4013].

Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration.

Ketogenic diet (KD), the "High-fat, low-carbohydrate, adequate-protein" diet strategy, replacing glucose with ketone bodies, is effective against several diseases, from intractable epileptic seizures, metabolic disorders, tumors, autosomal dominant polycystic kidney disease, and neurodegeneration to skeletal muscle atrophy and peripheral neuropathy. Key mechanisms include augmented mitochondrial efficiency, reduced oxidative stress, and regulated phospho-AMP-activated protein kinase, gamma-aminobutyric acid-glutamate, Na+/ K+ pump, leptin and adiponectin levels, ghrelin levels, lipogenesis, ketogenesis, lipolysis, and gluconeogenesis. In cancer cells, KD targets glucose metabolism, suppresses insulin-like growth factor-1 and PI3K/AKT/mTOR pathways, and reduces cancer cachexia and muscle waste and fatigue. An associated increased skeletal proliferator-activated receptor-γ coactivator-1α activity alters systemic ketone body homeostasis, contributing toward attenuated diabetic hyperketonemia. Antioxidative and anti-inflammatory properties enable KD enhance endurance and sports performances while preventing exercise-induced muscle and organ debility. KD reduces metabolic syndromes-associated allodynia and promotes peripheral axonal and sensory regeneration. This review enlightens effects of KD on various disease conditions. PRACTICAL APPLICATIONS: It is increasingly being realized that diet plays a very important role in our fight against several diseases. This can range from neurological disorders to diabetes and cancer. In this context, the potential of KD, the "High-fat, low-carbohydrate, adequate-protein" diet strategy, is increasingly being realized. In this article, we provide a comprehensive analysis of the benefits of KD against many diseases and discuss the underlying biochemical mechanisms. We hope that our write-up will stimulate further research on KD and help generate an interest for the populations to adopt this healthy diet. It can help overcome the problems associated with weight and dysregulated metabolism.

Function of Adenosine 2A Receptor in High-Fat Diet-Induced Peripheral Neuropathy.

Peripheral diabetic neuropathy (DPN) is a complication observed in up to half of all patients with type 2 diabetes. DPN has also been shown to be associated with obesity. High-fat diet (HFD) affects glucose metabolism, and the impaired glucose tolerance can lead to type 2 diabetes. There is evidence to suggest a role of adenosine 2A receptors (A2ARs) and semaphorin 3A (Sema3a) signaling in DPN. The link between the expression of Sema3a and A2AR in DPN was hypothesized, but the underlying mechanisms remain poorly understood. In this study, we investigated the regulation of Sema3a by A2AR in the spinal cord and the functional implications thereof in DPN. We examined the expression of A2ARs and Sema3a, as well as Neuropilin 1 and Plexin A, the coreceptors of Sema3a, in the dorsal horn of the lumbar spinal cord of an animal model with HFD-induced diabetes. Our results demonstrate that HFD dysregulates the A2AR-mediated Sema3a expression, with functional implications for the type 2 diabetes-induced peripheral neuropathy. These observations could stimulate clinical studies to improve our understanding on the subject.

Ketogenic Diet Potentiates Electrical Stimulation-Induced Peripheral Nerve Regeneration after Sciatic Nerve Crush Injury in Rats.

SCOPE: Recent findings indicate that the ketogenic diet (KD) is neuroprotective and electrical stimulation (ES) can improve functional recovery from peripheral nerve injury. However, it is not clear whether KD and ES play a synergistical role in the peripheral nerve recovery following injury. METHODS AND RESULTS: A KD consisting of a 3:1 ratio of fat to carbohydrate + protein is used and is coupled with ES treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery is evaluated by electromyography, and axonal regeneration and myelination by histological methods. The effects on insulin-like growth factor 1 (IGF-1) and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury, are also investigated. The combination of KD and ES synergistically increases muscle force in biceps femoris and gluteus maximus and prevents development of hypersensitivity in biceps femoris. It promotes peripheral nerve regeneration by increasing total axons, axon density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects are due to modulation of the IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue. CONCLUSION: The results establish that KD and ES promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach.

Folic acid and RAAS blockers in ischemia/reperfusion-induced hepatic injury: A current mechanistic concept for understanding the incidence, significance & outcome.

Hepatic ischemia-reperfusion injury (IRI) is not only one of the pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. IRI after liver transplant occurs due to in major resections and occlusion of vessels, or during the perioperative period, leads to acute liver failure which shows the dynamic process that involves two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury and has an impact on morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) is activated locally in the injured cells by the occurrence of I/R, which plays an essential role in the fate of the damaged tissue. However, a preclinical study explores the protective role of RAAS inhibitor in acute liver injury in a model of inflammation caused by ischemia and reperfusion. In-addition to RAAS blockers in monotherapy does not effectively block the complete pathway. Thus, the present study is designed to explore the effect of combined folic acid with RAAS blockers in combination, produce a synergistic effect. Moreover, in this review, we will describe the understanding of the possible incidence of downregulatory molecular mechanisms associated with renin-angiotensin-aldosterone system and the significance & outcome of the combination of folic acid and RAAS blockers in liver injury due to ischemia/reperfusion.

Role of epigenetic in leukemia: From mechanism to therapy.

Epigenetic variations can play remarkable roles in different normal and abnormal situations. Such variations have been shown to have a direct role in the pathogenesis of various diseases either through inhibition of tumor suppressor genes or increasing the expression of oncogenes. Enzymes involving in epigenetic machinery are the main actors in tuning the epigenetic-based controls on gene expressions. Aberrant expression of these enzymes can trigger big chaos in the cellular gene expression networks and finally lead to cancer progression. This situation has been shown in different types of leukemia, where high or low levels of an epigenetic enzyme are partly or highly responsible for the involvement or progression of a disease. DNA hypermethylation, different histone modifications, and aberrant miRNA expressions are three main epigenetic variations, which have been shown to play a role in leukemia progression. Epigenetic based treatments now are considered as novel and effective therapies in order to decrease the abnormal epigenetic modifications in patient cells. Different epigenetic-based approaches have been developed and tested to inhibit or reverse the unusual expression of epigenetic agents in leukemia. Acute myeloid leukemia (AML), the most prevalent acute leukemia in adults, is anaggressive hematological malignancy arising in hematopoietic stem and progenitor cells. With the exception of a few specific AML subtypes, the mainstays of treatment have not significantly changed over the last 20 years, and are still based on standard cytotoxic chemotherapy. In this review, we will discuss the recent development of therapeutics specifically targeting these key epigenetic programs in AML, describe their mechanism of action and present their current clinical development. Finally, we will discuss the opportunities presented by epigenetically targeted therapy in AML and will highlight future challenges ahead for the AML community, to ensure that this novel therapeutics are optimally translated into clinical practice and result in clinical improvement for AML patients.

High-fat diet enhances hepatic ischemia-reperfusion injury-induced apoptosis: Role of glucocorticoid receptors.

AIMS: The present study was designed to evaluate whether and how glucocorticoids can affect obesity-regulated hepatic ischemia-reperfusion (I/R) injury. MAIN METHODS: To this end, we first examined whether hydrocortisone (HCT) has protective effects on liver damage induced by hepatic I/R injury in mice receiving high fat diet treatment. We then explored the role of GR expression and phosphorylation in the anti-apoptotic effects of hydrocortisone upon hepatic I/R injury. KEY FINDINGS: We found that HCT reduced hepatic necrosis and inflammatory infiltration after hepatic I/R injury in mice that received high fat diet treatment. However, HCT lost the anti-apoptotic effects in high-fat diet treated mice. This phenomenon was associated with increased GRß expression, decreased basal levels of GR phosphorylation at Ser220 and lack of HCT-induced GR phosphorylation at Ser220 in high-fat diet treated mice. Additionally, basal levels of ERK phosphorylation was increased in high-fat diet treated mice, and I/R injury was associated with robustly increased ERK phosphorylation in high-fat diet treated mice, compared to normal diet treated mice. Furthermore, we demonstrated that high fat diet treated ERK1-/- mice exhibited robustly reduced apoptosis rate at 24h after reperfusion, compared to high fat diet treated wild-type mice. Importantly, there was a decreased level of GRß after high fat diet treatment in ERK1-/- mice. SIGNIFICANCE: These results together suggested that ERK1 phosphorylation plays a critical role in regulating GRß expression and HCT-induce GR phosphorylation at Ser220, which is critical for the anti-apoptotic effects HCT on hepatic I/R injury.

Endothelial progenitor cells promote tumor growth and progression by enhancing new vessel formation.

Tumor growth and progression require new blood vessel formation to deliver nutrients and oxygen for further cell proliferation and to create a neovascular network exit for tumor cell metastasis. Endothelial progenitor cells (EPCs) are a bone marrow (BM)-derived stem cell population that circulates in the peripheral circulation and homes to the tumor bed to participate in new blood vessel formation. In addition to structural support to nascent vessels, these cells can also regulate the angiogenic process by paracrine secretion of a number of proangiogenic growth factors and cytokines, thus playing a crucial role in tumor neovascularization and development. Inhibition of EPC-mediated new vessel formation may be a promising therapeutic strategy in tumor treatment. EPC-mediated neovascularization is a complex process that includes multiple steps and requires a series of cytokines and modulators, thus understanding the underlying mechanisms may provide anti-neovasculogenesis targets that may be blocked for the prevention of tumor development. The present review stresses the process and contribution of EPCs to the formation of new blood vessels in solid tumors, in an attempt to gain an improved understanding of the underlying cellular and molecular mechanisms involved, and to provide a potential effective therapeutic target for cancer treatment.

Protective effects of sevoflurane in hepatic ischemia-reperfusion injury.

The endothelial glycocalyx plays a critical role in the regulation of vascular structure and functions. Previous studies have demonstrated that sevoflurane, a volatile anesthetic, can preserve the endothelial glycocalyx in heart tissues against ischemia-reperfusion injury. However, little is known about the effects of sevoflurane pretreatment on the vascular structure and functions of liver tissues following ischemia-reperfusion injury. To this end, female Sprague-Dawley rats (n = 28) were anesthetized either with ketamine (80-120 mg/kg, i.p.) or with one minimum alveolar concentration (MAC) sevoflurane (2% v/v). Following in vivo hepatic ischemia procedure, the liver was isolated and reperfusion was produced. During the period of reperfusion, liver reperfusion samples were collected, and the concentrations of heparan sulfate and syndecan-1 (Syn-1), and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, were measured. The morphology of hepatocytes and endothelial glycocalyx were then assessed by using the light and electron microscopies, respectively. Ischemia-reperfusion increased the release of HS and Syn-1, and elevated the levels of ALT and AST in a time-dependent manner. However, sevoflurane pretreatment reduced the release of HS and Syn-1and attenuated the levels of ALT and AST, in a time-dependent manner, as compared with ketamine pretreatment. Furthermore, sevoflurane pretreatment decreased the shedding of endothelial glycocalyx and hepatocytes necrosis. Sevoflurane pretreatment preserved the endothelial glycocalyx in the liver tissue against ischemia-reperfusion injury. The effect appears to help protect hepatocytes against ischemia-reperfusion-induced necrosis.

Effect of laryngeal mask airway placement on the optimal site and success rate of venipuncture via the right internal jugular vein.

The placement of a laryngeal mask airway (LMA) changes the relative positions of the common carotid artery (CCA) and right internal jugular vein (IJV), thereby affecting venipuncture via the right IJV. Therefore, we went on to determine the optimal site for puncturing the IJV after LMA-Supreme™ placement. In this study, forty-six patients were placed with a LMA-Supreme™ (size 3 or 4), and the right IJV was punctured at either of the three points (anterior, middle or posterior point). The CCA diameters and overlap between the right IJV and CCA were recorded before and after the LMA-Supreme™ placement. Finally, the success rates of IJV puncturing at the three aforementioned points were compared. We found that the size of the LMA-Supreme™ had no effect on patient respiration during the procedure. Overlap between the right IJV and CCA at the anterior and middle points was significantly increased after size 3 LMA-Supreme™ placements; Size 4 masks decreased the CCA diameters at the middle and posterior points, and significantly increased overlap between the right IJV and CCA at all the three points; IJV punctures performed after placement of size 3 LMA-Supreme™ had higher success rate than those performed after placement of size 4 masks, and were less likely to result in accidental arterial puncture. In conclusion, our study demonstrated that placement of size 3 LMA-Supreme™ caused little change in overlapping between the right IJV and CCA and the incidence of accidental arterial puncture; particularly for punctures performed at the posterior point. Therefore, we recommend venipuncture at the posterior point after placement of a LMA-Supreme™.

MicroRNA-491-5p suppresses cervical cancer cell growth by targeting hTERT.

MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to regulate a variety of biological processes by targeting messenger RNA. MicroRNA-491-5p (miR-491-5p), an important miRNA, has been demonstrated to be involved in the processes of initiation and progression in several tumors. However, the precise biological function of miR-491-5p and its molecular mechanism in cervical cancer cells remain elusive. The present study was carried out to investigate the clinical significance and prognostic value of miR-491-5p expression in cervical cancer, and to evaluate the role of miR-491-5p and the underlying molecular mechanisms involved in cervical cancer. The results showed that miR-491-5p expression was significantly downregulated in cervical cancer tissues when compared with the corresponding adjacent normal tissues (P<0.001), and the value was negatively associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high histological grading and lymph node metastasis (P<0.01). The enforced expression of miR-491-5p in cervical cancer cells significantly inhibited proliferation, migration and invasion, induced cell apoptosis, and suppressed the tumor growth of the mouse model of HeLa cells. In addition, the dual-luciferase reporter assay revealed that human telomerase reverse transcriptase (hTERT) was identified as a novel target gene of miR-491-5p. Notably, it was found that miR-491-5p regulated the PI3K/AKT signaling pathway. These results suggested that targeting miR-491-5p is a strategy for blocking the development of cervical cancer.

Evaluation of biocompatibility and toxicity of biodegradable poly (DL-lactic acid) films.

Regeneration and functional recovery of nerves after peripheral nerve injury is the key to peripheral nerve repair. One of the putative therapeutic strategies is to use anti-adhesion polymer films, made of polymeric biomaterials. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been prepared using a method of phase transformation with biodegradable polylactic acid polymer as the substrate. This novel, anti-adhesion film has a porous structure, which provides better mechanical properties, better flexibility, more complete diffusion through the polymer of tissue biologic factors like growth factors, and more controllable degradation compared to traditional non-porous films. Little is known, however, about the in vitro and in vivo biocompatibility and cytotoxicity of this type of PDLLA film. Therefore, our aim was to evaluate the biocompatibility and cytotoxicity of this novel PDLLA film using various experimental methods, including a skin irritation test, MTT analysis, and the mouse bone marrow cell micronucleus test, as well as hematology or clinical chemistry measurements in rats after receiving sciatic nerve transection and anastomosis with wrapping of the anastomosis with DLLA films. We demonstrated that exposure to PDLLA film extracts did not generate apparent erythema or edema in rabbit skin and had no effect on the proliferation of Vero cells. Additionally, treatment with PDLLA film extracts did not alter the incidence of micronucleated polychromatic erythrocytes as compared with saline Treated group. Furthermore, implantation of PDLLA film did not alter liver or renal function as measured by serum levels of ALT, AST, TP, A/G, Cr, and BUN, and pathologic examinations showed that implantation of PDLLA film did not cause pathologic changes to the rat liver, kidney, pancreas, or spleen. Taken together, these results suggest that PDLLA films have excellent biocompatibility and no obvious toxicity in vivo, and may be used to prevent nerve adhesion, thereby promoting nerve regeneration.