TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.

Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

Metallic stent placement versus catheter drainage for malignant bilioenteric anastomotic stricture.

PURPOSE: The purpose of the study was to compare self-expandable metallic stent placement with catheter drainage for malignant bilioenteric anastomotic stricture in terms of efficacy and safety. MATERIALS AND METHODS: This study included 54 patients with malignant bilioenteric anastomotic stricture treated from March 2016 to February 2021. Twenty-seven patients underwent insertion of self-expandable metallic stent (Stent group); the remaining twenty-seven patients underwent internal-external catheter drainage (Catheter group). Technical success was defined as successful placement of stent or drainage catheter in the appropriate position; clinical success was defined as a 20% reduction in serum bilirubin within 1 week after the procedure, compared with baseline. Complications, duration to stent/catheter malfunction, and overall survival were evaluated. RESULTS: Technical success was achieved in all patients in both groups. In the Stent group, 21 patients received one stent and the other 6 patients required two stents. Clinical success rates were similar between the groups [Stent group, 92.6% (25/27); Catheter group, 88.9% (24/27)]. There were no major complications. The median duration to stent/catheter malfunction was significantly longer in the Stent group (130 days) than in the Catheter group (82 days; P = 0.010). The median overall survival was also significantly longer in the Stent group (187 days) than in the Catheter group (118 days; P = 0.038). CONCLUSION: Self-expandable metallic stent placement might be better than internal-external catheter drainage for malignant bilioenteric anastomotic stricture in terms of the duration before stent/catheter malfunction and patient survival.

Hepatic arterial infusion chemotherapy following simultaneous metallic stent placement and iodine-125 seed strands for advanced cholangiocarcinoma causing malignant obstructive jaundice: a propensity score matching study.

OBJECTIVE: This study aims to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) following the simultaneous placement of self-expandable metallic stent (SEMS) and iodine-125 (125I) seed strands for the management of advanced cholangiocarcinoma (CCA) patients presenting with malignant obstructive jaundice (MOJ). METHODS: Data from 74 patients with MOJ caused by advanced CCA treated with stent placement with 125I seed strands with or without HAIC between November 2015 and October 2020 were analysed retrospectively. Eighteen patients received 5 sessions of HAIC after SEMS placement with 125I seed strands (HAIC group), and 56 patients only underwent SEMS placement with 125I seed strands and served as controls (control group). HAIC consisted of infusions of gemcitabine (600-1000 mg/m2 given over 30 min) followed by oxaliplatin (60-100 mg/m2 given over 2 h), with an interval of 4 weeks. Propensity score matching (PSM) analysis was used to adjust for differences in the baseline characteristics of the groups (including age, total bilirubin, and serum alanine aminotransferase level). Overall survival (OS), stent patency, and adverse events were compared between the two groups. RESULTS: OS and stent patency were significantly better in patients in the HAIC group than in those in the control group (median survival time: before PSM, 362 vs. 185 days, p = 0.005; after PSM, 357 vs. 183 days, p = 0.012; median duration of stent patency: before PSM, 294 vs. 156 days, p = 0.001; after PSM, 287 vs. 183 days, p = 0.039). All adverse reactions were controllable by temporary symptomatic treatment. Serious complications and treatment-related deaths were not observed. CONCLUSION: Our preliminary study showed that HAIC following SEMS placement with 125I seed strands is effective and safe for the management of advanced CCA patients presenting with MOJ and could improve stent patency and patient survival.

MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated death worldwide. MicroRNA (miRNA)-32-5p is as an important cancer-associated miRNA in different types cancer. To date, the role of miR-32-5p in the migration and invasion of NSCLC remains unknown. In the present study, a Transwell assay was performed to investigate the role of miR-32-5p in lung adenocarcinoma. miR-32-5p expression level was determined via reverse transcription-quantitative PCR in 24 pairs of NSCLC and adjacent normal tissues. SMAD family member 3 (SMAD3) was considered as a novel target gene by luciferase reporter assay and western blot in NSCLC. The present study demonstrated that miR-32-5p is frequently downregulated in NSCLC tissues. The overexpression of miR-32-5p resulted in the inhibition of migratory and invasive abilities in NSCLC cells. Thus, SMAD3 was identified as a target of miR-32-5p, and its expression was negatively correlated with miR-32-5p expression in clinical NSCLC tissues. Overall, these findings indicate that miR-32-5p serves as a tumor suppressor by targeting SMAD3. Thus, miR-32-5p may be a potential therapeutic target for the treatment of lung adenocarcinoma.

The "Six-and-Twelve" Score for Recurrent HCC Patients Receiving TACE: Does it Still Work?

BACKGROUND: A new prognostic model, the "six-and-twelve" (SAT) score, was suggested to be effective in selecting ideal transarterial chemoembolization (TACE) candidates from treatment naïve hepatocellular carcinoma (HCC) patients. However, whether the SAT score could also be applied in recurrent HCC patients with prior curative-intent treatments remains unknown. We aimed to validate and compare SAT focussing on these patients. METHODS: From January 2014 to May 2019, 121 unresectable HCC patients with recurrence in Barcelona Clinic Liver Cancer (BCLC) A/B receiving TACE were enrolled. Survival distribution was evaluated by the Kaplan-Meier method compared by the log-rank test. Discriminatory ability was compared with the concordance index (C-index) to rank six prognostic systems (SAT, Four-and-seven, HAP, mHAP, mHAP2, mHAP3). The area under the curve (AUC) was performed to assess the mortality prediction at 1, 2, and 3 years. RESULTS: In recurrent HCC patients receiving TACE, SAT had better performances in survival distribution. Due to the highest C-index, SAT was deemed the first ranking prognostic score. In terms of mortality prediction at 1, 2 and 3 years, SAT had the best mortality prediction at 2 and 3 years and mHAP3 had the best mortality prediction at 1 year. CONCLUSIONS: Among the six prognostic systems analysed in ideal TACE patients with recurrences after curative-intent treatments, SAT was proven to be superior to other systems, suggesting that it could also be used in these patients.

Effect of recorded maternal voice on emergence agitation in children undergoing bilateral ophthalmic surgery: A randomised controlled trial.

AIM: This study was designed to investigate whether the playing-back of the recorded maternal voice through the headphones to children undergoing bilateral ophthalmic surgery has clinical effects on the incidence of emergence agitation, and the anaesthesia recovery course. METHODS: In this prospective, blinded and randomised study, 127 children, aged 2-8 years and undergoing bilateral ophthalmic surgery were randomly allocated to one of the two groups: group T (treatment group, listening to recorded mother's voice via headphones) or group C (control group, wearing headphones without auditory stimuli). The primary outcome was the incidence of emergence agitation, and the secondary outcomes were the awakening time, and the post-anaesthesia care unit (PACU) stay time. RESULTS: Children in the group of listening recorded mother's voice exhibited significantly low incidence of emergence agitation compared with those in the control group (32.8 vs. 55.6%; odds ratio (95% confidence interval): 0.39(0.19-0.80); P = 0.010). The awakening time was shorter in group T as compared to that in group C (22.9 (10.4) vs. 27.3 (13.7); P = 0.048). As results, the group T had significantly less PACU stay time with early discharge than the group C did (29.7 (12.1) vs. 34.8 (14.1); P = 0.031). CONCLUSIONS: Recorded mother's voice is an efficient method to reduce emergence agitation in children undergoing bilateral ophthalmic surgery with sevoflurane anaesthesia. Also, patients woke faster and PACU stay time was shorter in the mother's voice group as compared with the control group.

Percutaneous stent placement for malignant hilar biliary obstruction: side-by-side versus stent-in-stent technique.

BACKGROUND: Currently, side-by-side (SBS) and stent-in-stent (SIS) are the two main techniques for stent deployment to treat hilar biliary obstructions. Previous studies comparing these two techniques are very limited, and thus, no consensus has been reached on which technique is better. The purpose of this study is to compare the clinical efficacy and safety of SBS and SIS deployment via a percutaneous approach for malignant hilar biliary obstruction. METHODS: From July 2012 to April 2019, 65 patients with malignant hilar biliary obstruction who underwent bilateral stenting using either the SBS or SIS techniques were included in this study. Among them, 27 patients underwent SIS stent insertion (SIS group), and the remaining 38 patients underwent SBS stent insertion (SBS group). Technical success, improvement of jaundice, complications, duration of stent patency, and overall survival were evaluated. RESULTS: Technical success was achieved in all patients in the two groups. The serum bilirubin level decreased more rapidly 1 week after the procedures in the SBS group than in the SIS group (P = 0.02). Although the total complication rate did not differ between the two groups, cholangitis was found to be more frequent in the SIS group (P = 0.04). The median stent patency was significantly longer in the SBS group (149 days) than in the SIS group (75 days; P = 0.02). The median overall survival did not significantly differ between the two groups (SBS vs. SIS, 155 days vs. 143 days; P > 0.05). CONCLUSIONS: Percutaneous transhepatic bilateral stenting using either the SBS or SIS technique is safe and effective in the management of malignant hilar biliary obstruction. However, SBS offers a quicker improvement of jaundice, a lower incidence of cholangitis after the procedure, and a longer stent patency period than SIS.

The pH-dependent elastic properties of nanoscale DNA films and the resultant bending signals for microcantilever biosensors.

The diverse mechanical properties of nanoscale DNA films on solid substrates have a close correlation with complex detection signals of micro-/nano-devices. This paper is devoted to formulating several multiscale models to study the effect of pH-dependent ionic inhomogeneity on the graded elastic properties of nanoscale DNA films and the resultant bending deflections of microcantilever biosensors. First, a modified inverse Debye length is introduced to improve the classical Poisson-Boltzmann equation for the electrical potential of DNA films to consider the inhomogeneous effect of hydrogen ions. Second, the graded characteristics of the particle distribution are taken into consideration for an improvement in Parsegian's mesoscopic potential for both attraction-dominated and repulsion-dominated films. Third, by the improved interchain interaction potential and the thought experiment about the compression of a macroscopic continuum DNA bar, we investigate the diversity of the elastic properties of single-stranded DNA (ssDNA) films due to pH variations. The relevant theoretical predictions quantitatively or qualitatively agree well with the relevant DNA experiments on the electrical potential, film thickness, condensation force, elastic modulus, and microcantilever deflections. The competition between attraction and repulsion among the fixed charges and the free ions endows the DNA film with mechanical properties such as a remarkable size effect and a non-monotonic behavior, and a negative elastic modulus is first revealed in the attraction-dominated ssDNA film. There exists a transition between the pH-sensitive parameter interval and the pH-insensitive one for the bending signals of microcantilevers, which is predominated by the initial stress effect in the DNA film.

The prediction probabilities for emergence from sevoflurane anesthesia in children: A comparison of the perfusion index and the bispectral index.

BACKGROUND: Predicting recovery of consciousness is one of the most essential functions of anesthesia depth monitors in anesthesia practice. Perfusion index and bispectral index are 2 indicators of the anesthesia depth monitoring with different working principles. The progression of the anesthesia emergence stages reflected by those monitors has not been well understood, especially in pediatric patients. The goals of this study were to compare the prediction probabilities of perfusion index and bispectral index in predicting awakening and in differentiating the different levels of arousal during emergence after sevoflurane anesthesia in children undergoing open inguinal hernia repairs. METHODS: Forty-five patients, aged 1 to 5 years, ASA Status I or II and scheduled for elective open inguinal hernia repairs under general anesthesia were enrolled. The perfusion index and bispectral index were monitored simultaneously during anesthesia recovery. The University of Michigan Sedation Scale was applied to evaluate the clinical arousal levels during emergence. The prediction probability was used to assess the performance of perfusion index and bispectral index in predicting awakening and distinguishing different levels of arousal corresponding to the University of Michigan Sedation Scale during recovery. RESULTS: The prediction probability of perfusion index (PkPI-Awakening  = .81, 95% CI 0.73-0.89) in differentiating full consciousness from unconsciousness during recovery was comparable to that of bispectral index (PkBIS- Awakening  = .86, 95% CI 0.79-0.92) (P = .47). The prediction probability for perfusion index (PkPI-UMSS  = .61, 95% CI 0.55-0.73) and bispectral index (PkBIS-UMSS  = .64, 95% CI 0.53-0.69) had similar performance in distinguishing different University of Michigan Sedation Scale levels. CONCLUSION: Both the perfusion index and bispectral index performed comparably well in predicting awakening and different arousal levels when emerging from sevoflurane anesthesia in children.

Highly efficient mesophyll protoplast isolation and PEG-mediated transient gene expression for rapid and large-scale gene characterization in cassava (Manihot esculenta Crantz).

BACKGROUND: Cassava (Manihot esculenta Crantz) is a major crop extensively cultivated in the tropics as both an important source of calories and a promising source for biofuel production. Although stable gene expression have been used for transgenic breeding and gene function study, a quick, easy and large-scale transformation platform has been in urgent need for gene functional characterization, especially after the cassava full genome was sequenced. METHODS: Fully expanded leaves from in vitro plantlets of Manihot esculenta were used to optimize the concentrations of cellulase R-10 and macerozyme R-10 for obtaining protoplasts with the highest yield and viability. Then, the optimum conditions (PEG4000 concentration and transfection time) were determined for cassava protoplast transient gene expression. In addition, the reliability of the established protocol was confirmed for subcellular protein localization. RESULTS: In this work we optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and PEG-mediated transient gene expression in cassava. The suitable enzyme digestion system was established with the combination of 1.6% cellulase R-10 and 0.8% macerozyme R-10 for 16 h of digestion in the dark at 25 °C, resulting in the high yield (4.4 × 107 protoplasts/g FW) and vitality (92.6%) of mesophyll protoplasts. The maximum transfection efficiency (70.8%) was obtained with the incubation of the protoplasts/vector DNA mixture with 25% PEG4000 for 10 min. We validated the applicability of the system for studying the subcellular localization of MeSTP7 (an H+/monosaccharide cotransporter) with our transient expression protocol and a heterologous Arabidopsis transient gene expression system. CONCLUSION: We optimized the main influencing factors and developed an efficient mesophyll protoplast isolation and transient gene expression in cassava, which will facilitate large-scale characterization of genes and pathways in cassava.

Effect of surface charge state on the surface stress of a microcantilever.

The surface charge state at a liquid-solid interface is important to the variations in the physical/chemical properties of adsorbate film such as surface stress and the ensuing tip deflection of the microcantilever. The well-known Stoney's equation, derived more than 100 years ago, conceals the film electrical properties with the replacement of substrate deformation induced by adsorptions of particles. This implicit expression provides a shortcut to circumvent the difficulty in identifying some film properties, however, it limits the capacity to ascertain the relation between surface stress variation and the surface charge state. In this paper, we present an analytical expression to quantify the cantilever deflection/surface stress and the film potential difference by combining the piezoelectric theory and Poisson-Boltzmann equation for electrolyte solution. This updated version indicates that the two linear correlations between surface stress and surface charge density or the bias voltage are not contradictory, but two aspects of one thing under different conditions. Based on Parsegian's mesoscopic interaction potential, a multiscale prediction for the piezoelectric coefficient of double-stranded DNA (dsDNA) film is done, and the results show that the distinctive size effect with variations in salt concentration and nucleotide number provides us with an opportunity to obtain a more sensitive potential-actuated microcantilever sensor by careful control of packing conditions.

Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion.

OBJECTIVES: Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. MATERIALS AND METHODS: Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman's rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. RESULTS: In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01)/clinical staging (r = -0.41, P<0.01)/tumor stage (r = -0.28, P = 0.02)/nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. CONCLUSION: Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.

Consequence of dexmedetomidine on emergence delirium following sevoflurane anesthesia in children with cerebral palsy.

Children with cerebral palsy can demonstrate irritability following emergence from general anaesthesia. As well, an elevated rate of emergence delirium (ED) in children has been associated with the application of sevoflurane. The current study's intent is to administer dexmedetomidine, in a single dosage administration, at the initial phase of sevoflurane based anesthesia with regard to the occurrence and severity of ED in children afflicted with cerebral palsy. Participating in the study (American Society of Anesthesiologists I-II) are eighty children ranging in ages two through twelve years. They would be anaesthetised with sevoflurane based anesthesia while undergoing lower limb surgical procedures. The participants were equally distributed to either Group c or Group D. Group C was administered 10 ml saline 0.9%, and Group D was administered dexmedetomidine 0.5 µg•kg(-1). Five minutes prior to commencement of the surgical procedures, the participants received the prescribed pharmaceutical dosages under the anesthesia of sevoflurane. In order to sustain the BIS values in a range of 45 and 55, at 60 second increments, endtidal sevoflurane concentrations (ETsev) were modified. After conclusion of the surgical procedures, in post anesthesia care unit (PACU), the frequency of ED was gauged with Aonos four point scale and the severity of ED was gauged with pediatric anesthesia emergence delirium scale upon admission (T0), after intervals of five minutes (T5), fifteen minutes (T15) and thirty minutes (T30). Extubation time, emergence time and length of at stay at the PACU were assessed. Relative to Group C, participants of Group D exhibited noticeably shortened times of emergence, extubation and PACU duration of stay. Prior to surgical incision, ETsev was elevated in the control group, (1.9±0.2 vs 1.6±0.3; P = 0.023) and amid the initial 20 minutes following the surgical incision (1.6±0.2 vs 1.1±0.2; P = 0.016). At intervals of commencement, T0, of five minutes (T5) and fifteen minutes T15, Group D exhibited lower occurrences and severity of ED than those participants in Group C. Dexmedetomidine, given as a bolus dose post induction, was effective in reducing the occurrence and severity of emergence delirium in children with cerebral palsy who were undergoing lower limb surgical procedures under sevoflurane anaesthesia.

Noninvasive cardiac output monitoring using bioreactance-based technique in pediatric patients with or without ventricular septal defect during anesthesia: in comparison with echocardiography.

BACKGROUND: We evaluated the use of bioreactance-based noninvasive cardiac output (CO) monitoring technique (NICOM(™), CO(NICOM)) in pediatric patients with or without ventricular septal defect (VSD) during anesthesia induction to determine its agreement with the measurements assessed by echocardiography (echo, CO(ECHO)). METHODS: Twenty-eight pediatric patients with normal heart anatomy (group NHA) and 32 with isolated ventricular septal defects (group VSD) were included in this study. The cardiac output was measured simultaneously in minute-by-minute using NICOM and echo (Simpson's rule) during anesthesia induction and intubation. Linear regression and revised Bland-Altman analyses were performed to evaluate the agreement by comparing the paired CO results. The mean percent error ((CO(ECHO)-CO(NICOM))/CO(ECHO) × 100%) was used to assess the impact of congenital heart disease on the agreement. RESULTS: The measurements of CO by NICOM and echo techniques were highly correlated in group NHA (γ = 0.96, P < 0.005) and VSD (γ = 0.84, P < 0.005). The mean bias (CO(ECHO) - CO(NICOM)) between the two methods was 0.03 and 0.31 l·min(-1) with the limits of agreement (LOA) -0.29 to +0.35 l·min(-1) and -0.44 to +1.05 l·min(-1), which include 96.9% (31/32) and 89.3% (25/28) of all patients' different data in group NHA and VSD, respectively. The median percent errors were significantly lower at all time points in group NHA than those in group VSD (all P < 0.05). CONCLUSION: In children without heart defects, the CO measured by NICOM shows a good agreement with the echo during anesthesia induction. The NICOM technique underestimates echo although a strong correlation exists between two methods in children with ventricular septal defect.

Nuclear translocation of MRP1 contributes to multidrug resistance of mucoepidermoid carcinoma.

Multidrug resistance-related protein 1 (MRP1 or ABCC1), a membrane-bound energy-dependent efflux transporter, is overexpressed in several kinds of multidrug-resistant cell lines and related to multidrug-resistance (MDR) of various cancers. In this study, we investigated whether MRP1 was involved in the chemoresistance of mucoepidermoid carcinoma (MEC). We demonstrated that down-regulation of MRP1 in MC3/5FU, a drug-resistant MEC cell line, by RNA interference increased the drug sensitivity of the cells to 5-fluorouracil, doxorubicin, pharmorubicin, bleomycin-A5, cis-platinum and taxol. However, no significant quantitative difference of MRP1 mRNA and protein expression was found between MC3/5FU cells and its parental cell line (MC3) as determined by RT-PCR and Western blot. Interestingly, MRP1 was translocated from the cytoplasmic membrane of the MC3 cells to the nuclei of MC3/5FU cells as revealed by indirect immunofluorescence staining. Furthermore, MRP1 down-regulation mainly decreased the nuclear expression of MRP1 rather than the cytoplasmic membrane expression. Our results suggested that MRP1 was involved in the chemoresistance of MEC and MRP1 may confer drug-resistance by a mechanism associated with its nuclear translocation.

Baicalin induces human mucoepidermoid carcinoma Mc3 cells apoptosis in vitro and in vivo.

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor in salivary glands and high-grade MEC in particular demonstrates little response to chemotherapy which has been used largely for palliative treatment of metastatic disease. Baicalin, one of the main active compounds of Scutellaria baicalensis, possesses anti-inflammatory, antioxidant and antitumor properties. In the present study, we investigated the growth inhibiting and apoptosis-inducing effects of baicalin on a highly metastatic human mucoepidermoid carcinoma cell line Mc3 for the first time. Baicalin exerted dose- and time-dependent antiproliferative potential against Mc3 cells as assessed by MTT assay. Baicalin treatment of Mc3 cells resulted in an accumulation of cells at the G0/G1 and G2/M phase with a concomitant decrease in cells processing to S phase as assessed by flow cytometry. Furthermore, baicalin induced apoptosis of Mc3 cells as determined by annexin V binding and PI dual staining, DNA fragmentation, nuclear condensation and in vivo tumor inhabitation. Rhodamine 123 assay indicated that baicalin caused cytotoxicity and induced apoptosis through decreasing the mitochondrial membrane potential in Mc3 cells. Our results suggest that baicalin seems to be very attractive as a new anticancer drug and a potential chemotherapeutic agent against human high-grade mucoepidermoid carcinoma.

[PTEN tumor suppressor gene combined with doxycycline inhibites telomerase activity in human mucoepidermoid carcinoma cell line].

OBJECTIVE: To investigate the effect of PTEN tumor suppressor gene combined with doxycycline on telomerase activity in human mucoepidermoid carcinoma cell line. METHODS: The wild-type PTEN tumor suppressor gene or empty vector was introduced into mucoepidermoid carcinoma cell line in vitro, then the cancer cells were treated with doxycycline. Cancer cell survival was determined by MTT assay. Telomerase activity was determined using telomerase repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA). RESULTS: Compared to the control cells, cancer cells transfected with the wild-type PTEN gene showed growth inhibition and increased sensitivity to doxycycyline, and the ratio of augment of drug sensitivity was 1.65-4.75. The telomerase activity in cancer cells treared with PTEN gene transfection or doxycycline alone decreased, however, telomerase activity in combined group decreased more remarkably. CONCLUSION: PTEN gene in combination with doxycycline has significant inhibitory effect on telomerase activity in cancer cells.