MiR-875 can regulate the proliferation and apoptosis of non-small cell lung cancer cells via targeting SOCS2.

OBJECTIVE: To investigate the effect of miR-875 on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cancer cell line A549 and the related mechanism. PATIENTS AND METHODS: 30 paired tumor tissue and the adjacent tissue were collected. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) has been performed to detect the expression of miR-875 in NSCLC tissues and adjacent normal tissues. Moreover, suppressor of cytokine signaling 2 (SOCS2) has been predicted as a target of miR-875, and Dual-Luciferase reporter assay has been performed to confirm the targeting relationship; furthermore, the expression of SOCS2 in tumor tissue and the adjacent tissue were compared. Next, human NSCLC cell line A549 cells were cultured and transfected with miR-875 inhibitor with or without SOCS2 siRNA, and the proliferation and apoptosis of the cells were evaluated by Cell Counting Kit (CCK-8) and flow cytometry methods. Finally, the relative protein expression of Wnt and ß-catenin were analyzed by Western blot analysis. RESULTS: MiR-875 was significantly up-regulated in NSCLC tissues compared with the adjacent tissues. SOCS2 was confirmed as a target of miR-875, and the expression of SOCS2 was markedly decreased in NSCLC tissues. Moreover, the knockdown of miR-875 inhibited the proliferation and promoted the apoptosis of A549 cells, while transfection of SOCS2 siRNA can block miR-875 inhibitor-induced anti-proliferative effects. Finally, the transfection of miR-875 inhibitor decreased the expression of Wnt and ß-catenin, and SOCS2 siRNA can reverse the effect. CONCLUSIONS: MiR-875 may regulate the proliferation and apoptosis of NSCLC cells via targeting SOCS2, suggesting that miR-875 has the potential to become a therapeutic target for the treatment in NSCLC.

Anti-malarial chemoprophylaxis following evacuation from Afghanistan.

UK forces deployed to Afghanistan between March and November are prescribed anti-malarial chemoprophylaxis (AMC). In 2007 an audit showed poor pre-injury AMC compliance and a prescription rate of 50% amongst those casualties evacuated to Role 4. We re-audited the post-deployment AMC prescribing practice for casualties from Afghanistan for the 2008 and half of the 2009 malaria season. Using the Role 4 prescribing information and communication system (PICS), a retrospective AMC search for Proguanil, Chloroquine, Doxycycline, Mefloquine and Malarone was performed on these casualties. Only five out of 305 (1.64%) inpatients were prescribed appropriate post-deployment AMC medication. Awareness of the need to prescribe AMC following evacuation remains poor, and may be improved by recording AMC compliance in field medical records and modifying the PICS software.

MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer.

BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover, miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328 expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05, Pearson's correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy.

Field intensive care--weaning and extubation.

Injury following ballistic trauma is the most prevalent indication for providing organ system support within an ICU in the field. Following damage control surgery, postoperative ventilatory support may be required, but multiple factors may influence the indications for and duration of invasive mechanical ventilation. Ballistic trauma and surgery may trigger the systemic inflammatory response syndrome (SIRS) and are important causative factors in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, their pathophysiological effect on the respiratory system is unpredictable and variable. Invasive mechanical ventilation is associated with numerous complications and the return to spontaneous ventilation has many physiological benefits. Following trauma, shorter periods of ICU sedation-amnesia and a protocol for early weaning and extubation, may minimize complications and have a beneficial effect on their psychological recovery. In the presence of stable respiratory function, appropriate analgesia and favourable operational and transfer criteria, we believe that the prompt restoration of spontaneous ventilation and early tracheal extubation should be a clinical objective for casualties within the field ICU.

Pathways through the nose for nasal intubation: a comparison of three endotracheal tubes.

BACKGROUND: In nasotracheal intubation, there are two main pathways in the nostril through which the endotracheal tube may pass. The lower pathway lies along the floor of the nose underneath the inferior turbinate. The upper pathway lies above the inferior turbinate, just below the middle turbinate. The lower pathway may be considered to be the safer route as it is located away from the middle turbinate and cribiform plate. METHODS: We conducted a randomized controlled trial comparing the frequency with which preformed, reinforced, and thermosoftened preformed tubes pass through upper and lower pathways. Ninety-two maxillofacial patients requiring nasotracheal intubation as part of their anaesthetic management were studied. Two patients were excluded from the study at endoscopy because of atypical nasal anatomy. After the induction of general anaesthesia, a standardized traditional nasal intubation was performed with a Macintosh laryngoscope, the operators endeavouring to direct the tube along the floor of the nose. Fibreoptic nasendoscopy was then performed by passing the tip of the fibrescope 2-3 cm into the nasal cavity above and below the tube, to identify the pathway taken. RESULTS: Data were analysed on 30 patients in each group. Five (16.7%) preformed tubes, 17 (56.7%) reinforced tubes, and 6 (20%) thermosoftened preformed tubes passed through the lower pathway. Significantly more reinforced tubes took the preferred pathway (P=0.001). Tubes passing through the upper pathway caused significantly more epistaxis than tubes passing through the lower pathway (P=0.003). CONCLUSIONS: Endotracheal tubes, particularly preformed tubes, frequently take the less favourable pathway during nasotracheal intubation, in spite of specific attempts to avoid this.

The management of difficult direct laryngoscopy and intubation in a field hospital: an alternative to fibreoptic endoscopy.

Fibreoptic endoscopy and intubation continues to be recommended in guidelines for the management of difficult airways. Since fibrescopes are unavailable within United Kingdom field hospitals, an alternative is needed. The Airtraq optical laryngoscope is a versatile, inexpensive, single-use option, which could readily fill this void. It is easy to use and provides a full view of the glottis when direct laryngoscopy has failed. Its introduction will reinforce existing difficult airway equipment and simplify the management of 'can ventilate - can't intubate' patients.

Cardiovascular responses following laryngoscope assisted, fibreoptic orotracheal intubation.

The Macintosh laryngoscope has recently been used successfully as an airway clearance device during fibreoptic intubation in patients who presented difficult intubation, but it is not known whether this approach will increase the pressor response to intubation. The aim of this investigation was to compare the cardiovascular responses of this method of facilitating airway clearance with the lingual traction plus jaw thrust method. 40 ASA I or II adult patients were given a standardised general anaesthetic and were randomly allocated to receive either lingual traction with jaw thrust (lingual traction group) or direct laryngoscopy with a Macintosh laryngoscope (laryngoscopy group) as the airway clearance manoeuvre prior to fibreoptic orotracheal intubation. Following intubation there was a significant rise in arterial pressure above pre-induction levels in both groups (p < 0.05); however, the arterial pressure in the laryngoscopy group was significantly greater than that in the lingual traction group (systolic: p = 0.031, diastolic: p = 0.002). It appears therefore that the mechanical stimulus of the Macintosh laryngoscopy evokes a greater pressor response than that of lingual traction plus jaw thrust when these interventions are followed by fibreoptic intubation.