The Long Non-Coding RNA AC006329.1 Facilitates Hepatocellular Carcinoma Progression and Metastasis by Regulating miR-127-5p/SHC3/ERK Axis.

Purpose: Hepatocellular carcinoma(HCC) is the most common type of liver cancer and the sixth largest common cancer worldwide. Although surgical resection, hepatic arterial chemoembolization, targeted drugs and immunotherapy are currently available, the mortality of advanced patients remains high. Therefore, new therapeutic targets are urgently needed. In recent years, many studies have found that The long non-coding RNA(lncRNA) has multiple functions in human tumors, including participating in epigenetic, transcriptional, post-transcriptional and translational regulation, and is closely related to the progression of HCC. The purpose of this study was to investigate the role of AC006329.1 in HCC progression and provide theoretical guidance for finding new targets. Patients and Methods: AC006329.1 was screened out by transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Then a series of functional tests in vivo and in vitro were conducted to investigate the effects of AC006329.1 on HCC progression and metastasis. Epithelial-mesenchymal transformation (EMT) of HCC was detected by Western blot and immunofluorescence staining. The targeted miRNA and downstream gene of AC006329.1 were predicted by databases and the pathway regulation axis eventually validated by dual luciferase reporter assays, qRT-PCR and WB. Results: AC006329.1 was found high expressed in HCC tissues and cell lines by qRT-PCR. The prognosis of HCC patients with high expressed AC006329.1 was poor. In vitro and in vivo, overexpression of AC006329.1 can promote the progression, metastasis and EMT of HCC by acting as a sponge of miR-127-5p to increase the expression of SHC3. In addition, up-regulation of miR-127-5p or knockdown of SHC3 can both reverse the promoting effects of AC006329.1 on progression, metastasis and EMT of HCC. Finally, WB and qRT-PCR analysis was discovered that AC006329.1 can facilitate HCC progression, EMT and metastasis by competitively inhibiting miR-127-5p to activate SHC3/ERK signaling pathway. Conclusion: These above experimental results confirmed that AC006329.1 can facilitate HCC progression, EMT and metastasis by acting as a competing endogenous RNA (ceRNA) to inhibit miR-127-5p and activate SHC3/ERK signaling pathway.

Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol).

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol-ene "photo-click" reaction or a "one-pot" thiol-maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.

Usefulness of Deep Hypothermic Circulatory Arrest and Regional Cerebral Perfusion in Children.

To compare the safety and usefulness of deep hypothermic circulatory arrest (DHCA) and regional cerebral perfusion (RCP) during pediatric open heart surgery. Between January 1, 2004 and September 30, 2012, 1250 children with congenital cardiac defect underwent corrective operation with the DHCA or RCP technique in the Shanghai Children's Medical Center. Of them, 947 cases underwent the operation with the aid of DHCA (DHCA group), and 303 cases with RCP (RCP group). The mean DHCA time was 30.64±15.81 (7-63) minutes and mean RCP time was 36.18±12.86 (10-82) minutes. The mortality rate was 7.18% (68/947) and 6.60% (20/30) in two groups, respectively. The postoperative incidences of temporary and permanent neurological dysfunction were 6.23% (59/947) in the DHCA group and 2.64% (8/303) in the RCP group (p<0.01). The incidence of other complications such as low cardiac output, renal dysfunction, and lung issues are similar in both groups. RCP is a reliable technique for cerebral protection and it facilitates time-consuming corrected procedures for complex congenital cardiac defect repair procedures.

Pulsatile flow improves cerebral blood flow in pediatric cardiopulmonary bypass.

The objective of this study was to evaluate the effect of pulsatile flow on cerebral blood flow (CBF) in infants with the use of a mild hypothermic cardiopulmonary bypass (CPB). Thirty infants scheduled for open heart surgery were randomized to the pulsatile group (Group P, n = 15) and nonpulsatile group (Group NP, n = 15). In Group P, pulsatile perfusion was applied during the aortic cross-clamping period, whereas nonpulsatile perfusion was used in Group NP. The systolic peak velocity (Vs), the end of diastolic velocity (Vd), the mean velocity (Vm), and the pulsatility index (PI) and the resistance index (RI) of the middle cerebral artery were measured by a transcranial Doppler (TCD) ultrasound after anesthesia (T1; baseline), at the beginning of CPB (T2), 10 min after aortic cross-clamping (T3), 3 min after declamping (T4), at the cessation of CPB (T5), and at the end of the operation (T6). During T3 and T4, the Vs in Group P was significantly higher than in Group NP. However, there were no statistically significant differences between Vd and Vm. The PI and RI in Group P were also higher than those in Group NP (both P < 0.05). During T5, Vd and Vm were higher in Group P (P < 0.05), whereas there was no difference in Vs. Additionally, PI and RI in Group P were significantly lower than those in Group NP (P < 0.05). However, there was no difference during T6. Pulsatile perfusion may increase CBF and decrease cerebral vascular resistance in the early period after mild hypothermic CPB.

Effect of flow rate, negative pressure, and duration of modified ultrafiltration on hemodynamics and inflammatory mediators.

The objective of this study was to evaluate the effect of flow rate, negative pressure, and duration on modified ultrafiltration (MUF). Eighty children weighing less than 10 kg with congenital heart disease were randomly divided into four groups: group C (conventional MUF); group H (high flow rate MUF); group P (high negative pressure MUF); and group L (long duration, high flow rate MUF). The changes in body weight, hematocrit, and hemodynamics were recorded. Tumor necrosis factor and interleukin-6 were measured before bypass, bypass stop, and MUF cessation. The durations of MUF in groups H and P were significantly shorter than in the other two groups; the volume filtered in group L was much greater than in the other three groups. The changes of bodyweight, heart rate, blood pressure, and hematocrit were similar in all groups. The increased extent of inflammatory mediators was a little lower in group L. Modified ultrafiltration can reverse hemodilution and improve cardiac function even with high flow rate or negative pressure. Prolonging the duration of MUF can filter out more inflammatory mediators, but the increased trend cannot be reversed in 15 minutes.

Seven years' experience of pediatric cardiopulmonary bypass: 8685 cases in Shanghai Children's Medical Center.

Herein we report our 7-year-experience of cardiopulmonary bypass. Between April 1, 1999, and December 31, 2005, 8685 children with congenital heart disease underwent cardiopulmonary bypass in Shanghai Children's Medical Center. The number of cases increased every year, and the number of patients younger than 1 year or weighing <10 kg also increased. Different bypass technology was adapted according to the operation. Roller pumps were used for most of the patients. Crystal cardioplegia (St. Thomas II) was used until blood cardioplegia was introduced in 2003. Ultrafiltrators were set up for infants weighing <10 kg. Mortality rates per year ranged from 1.81% to 3.70%. The most frequent complication was low cardiac output, about 12% in recent years. Arrhythmia, infection, and lung complications were the next three most frequent problems after surgery.

[Arterial switch operation for transposition of the great arteries and double outlet of right ventricle with subpulmonary ventricular septum defect].

OBJECTIVE: To summarize the clinical experience on the arterial switch operation for complex congenital heart disease in recent 3 years in our hospital. METHODS: Sixty-one patients with complex congenital heart disease received by arterial switch operation from Jan 2000 to May 2003. There were 26 patients with transposition of the great arteries and intact ventricular septum (TGA-IVS), 19 patients with transposition of the great arteries and ventricular septal defect (TGA-VSD) and 16 patients with double outlet of right ventricle with subpulmonary ventricular septum defect (Taussig-Bing). RESULTS: There were 2 death among TGA-IVS cases, 4 deaths among TGA-VSD cases and 4 deaths among Taussig-Bing cases. The total operative mortality was 16%. All patients were followed up 3 months to 3 years. In all patients, the cyanosis disappeared and the physical activities increased obviously. One patients with Taussig-Bing keep moderate mitral valve reflux unchanged, 2 patients with TGA had pulmonary and aortic supra-valve stenosis with 40 mmHg pressure gradient. One patient with subpulmonary stenosis and residual VSD was re-operated 3 months later. All survivor had good heart function. CONCLUSIONS: The effect of arterial switch operation on the treatment of TGA was well accepted in this study. The procedure used in treatment on Taussig-Bing can prevent pulmonary obstruction and avoid the complication of left ventricular outflow tract obstruction caused by intraventricular repair.