Biological activity of a new recombinant human coagulation factor VIII and its efficacy in a small animal model.

Deficiency in human coagulation factor VIII (FVIII) causes hemophilia A (HA). Patients with HA may suffer from spontaneous bleeding, which can be life-threatening. Recombinant FVIII (rFVIII) is an established treatment and prevention agent for bleeding in patients with HA. Human plasma-derived FVIII (pdFVIII), commonly used in clinical practice, is relatively difficult to prepare. In this study, we developed a novel B-domain-deleted rFVIII, produced and formulated without the use of animal or human serum-derived components. rFVIII promoted the generation of activated factor X and downstream thrombin, and, similar to that of other available FVIII preparations, its activity was inhibited by FVIII inhibitors. In addition, rFVIII has ideal binding affinity to human von Willebrand factor. Activated FVIII (FVIIIa) could be degraded by activated protein C and lose its procoagulant activity. In vitro, commercially available recombinant FVIII (Xyntha) and pdFVIII were used as controls, and there were no statistical differences between rFVIII and commercial FVIII preparations, which demonstrates the satisfactory efficacy and potency of rFVIII. In vivo, HA mice showed that infusion of rFVIII rapidly corrected activated partial thromboplastin time, similar to Xyntha. Moreover, different batches of rFVIII were comparable. Overall, our results demonstrate the potential of rFVIII as an effective strategy for the treatment of FVIII deficiency.

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.

Intravenous lidocaine simultaneously infused with sufentanil to accelerate gastrointestinal function recovery in patients after thoracolumbar surgery: a prospective, randomized, double-blind controlled study.

PURPOSE: Postoperative gastrointestinal dysfunction is one of the common complications of surgery, especially after surgery for a thoracolumbar spinal fracture. Intravenous lidocaine is a potential method to improve postoperative gastrointestinal function in surgical patients, reduce opioid use and shorten hospital stays. The purpose of this study is to explore the effect of intravenous lidocaine on the recovery of gastrointestinal function in patients after thoracolumbar surgery. METHODS: In this study, 48 eligible patients undergoing elective thoracolumbar spine fractures resection and internal fixation surgery were enrolled to receive intravenous injections of lidocaine in different concentrations during the perioperative period. Patients were randomly divided into three groups: control group (group A), low concentration of lidocaine group (group B) and high concentration of lidocaine group (group C), 16 patients in each group. First postoperative exhaust time, numbers of bowel sound at preoperative and postoperative 3, 6, 12, 24 h, pain scores at postoperative 0, 3, 6, 12, 24, 48 h, total sufentanil use in PACU and perioperative periods, postoperative hospital stay and analgesic remedy within postoperative 48 h were recorded and compared. The primary endpoints include: the time of first flatus passage after the operation, the number of bowel sounds per minute counted with stethoscope at 30 min before anesthesia induction and at 3, 6, 12 and 24 h postoperative. The secondary endpoints included: the pain scores at PACU (after entering into PACU), 3, 6, 12, 24 and 48 h postoperative, the amount of sufentanil administrated by intravenous push during operation and the numbers of patients needed rescuing sufentanil in PACU, and the numbers of patients needed administration of gastric motility drugs or non-steroidal analgesics at ward within 48 h postoperation, length of hospital stay (from the first day after surgery to discharge from hospital) and the incidence of adverse reactions. RESULTS: Compared with group A, the first postoperative exhaust time in group B and C occurred much earlier (23.3 ± 11.0 h vs. 16.0 ± 6.6 h, 16.6 ± 5.1 h, P < 0.05). Compared with preoperation, the numbers of bowel sound significantly increased at 24 h postoperatively in group B, while group B at 6 h and group C at 6 and 24 h postoperatively had significantly more active bowel sounds compared to group A (P < 0.05). There were no remarkable differences in VAS scores within 12 h postoperatively among three groups, and however, significantly lower VAS scores were found at 12, 24 and 48 h postoperatively in group C when comparing to Group A (p < 0.05). There was no statistical significance in the incidence of postoperative flatulence and nausea and vomiting, the number of patients needed rescuing sufentanil in PACU, the length of postoperative hospital stay and the number of patients requiring non-steroidal analgesics at ward within 48 h postoperation. CONCLUSIONS: Intravenous lidocaine infusion together with patient-controlled analgesia of sufentanil expedited the early recovery of gastrointestinal function and improved analgesic quality of sefentanyl in patients undergoing thoracolumbar surgeries.

Novel "Z" Technique to Overcome Warping of Costal Cartilage.

BACKGROUND: Dorsal augmentation with costal cartilage is generally used for aesthetic rhinoplasty. However, the tendency of costal cartilage to warp may jeopardize the aesthetic outcome. OBJECTIVES: The aim of this study was to describe a new "Z" technique to overcome the warping of costal cartilage after implantation and to evaluate the efficacy of this technique in vitro. METHODS: A total of 31 pairs of porcine costal cartilage grafts (40 mm × 10 mm × 5 mm) were obtained and kept in Dulbecco's Modified Eagle Medium (Sigma-Aldrich, St. Louis, MO) to maintain cell viability. Paired grafts were obtained and randomly allocated for preparation by the accordion technique and the "Z" technique. Standardized photographs (obtained immediately after operation and at 4 weeks) were used for warping analysis. Biomechanical testing was performed to measure the graft's capacity to resist deformation by an external force. RESULTS: Cell viability of the grafts at 4 weeks was comparably good in the accordion group and the Z group (61.88% ± 4.47% vs 67.48% ± 7.03%, P = 0.55). Warping angle was comparable between the 2 groups (P > 0.01). The capacity to resist external force was significantly better in the Z group; the force needed to cause deformation was 3.98 ± 1.04 N in the Z group vs 1.61 ± 0.47 N in the accordion group in lateral view (P < 0.0001), and 1.33 ± 0.41 N vs 0.96 ± 0.24 N, respectively, in frontal view (P = 0.0013). CONCLUSIONS: The "Z" technique appears to be a simple and effective method to minimize the tendency of costal cartilage to warp after implantation.

Septal Extension Grafts in Rabbit Models: A Comparative Study Between Costal and Conchal Cartilage Grafts.

BACKGROUND: The septal extension graft (SEG) has become the preferred augmentation rhinoplasty technique for Asian people due to its superiority in correcting tip projection and rotation. OBJECTIVES: The aim of this study was to build a rabbit model for SEG surgery and to compare the postoperative stability of nasal tip support provided by bilateral batten costal and conchal cartilage extension grafts. METHODS: Twenty rabbits underwent SEG surgery with either bilateral batten costal cartilage graft (Group A) or bilateral batten conchal cartilage graft (Group B). Serial photographs were obtained to evaluate the change of the nasal tip shape and graft shape. The observed indices include tip projection, tip angle, shape of extension graft, and histologic features of the extension graft. RESULTS: Twelve weeks after the operation, 1 costal extension graft in Group A (1/10) and 3 conchal extension grafts in Group B (3/10) were reabsorbed. The costal cartilage graft showed better exterior results than conchal cartilage graft in terms of tip projection and angle relapse rate (13.01% vs 25.02% and 15.18% vs 28.73%; P < .05). The costal cartilage graft maintained its structure better than the conchal cartilage graft. A greater degree of calcification and more fibrous capsules around the extension graft were found in Group A. CONCLUSIONS: A rhinoplasty rabbit model was established to compare costal and conchal autologous cartilages for SEG. This model may serve as a training tool for rhinoplasty surgeons. The costal cartilage extension graft is more reliable in terms of stability and should be given more attention.

Effect of lidocaine perioperative infusion on chronic postsurgical pain in patients undergoing thoracoscopic radical pneumonectomy.

BACKGROUND: Thoracoscopic radical pneumonectomy is associated with a high incidence of postoperative chronic pain. Studies on the benefits of lidocaine intravenous infusion during the perioperative period were still controversial in thoracoscopic surgery. METHODS: Sixty-four lung cancer patients scheduled for thoracoscopic radical pneumonectomy were randomly divided into two groups: normal saline group (control group) or lidocaine group. In the lidocaine group, 1.5 mg/kg lidocaine was administered during the anesthesia induction, and 2 mg·kg-1·h-1 lidocaine was continuously intravenous infused until the end of the surgery. After the surgery, a mixture of 2 µg/kg sufentanil and 10 mg/kg lidocaine was continuously intravenous infused by postoperative patient-controlled intravenous analgesia pump (100 ml). In the control group, the same volume of normal saline was administered according to the calculation of lidocaine during anesthesia induction, maintenance and postoperative patient-controlled intravenous analgesia. The primary outcome was the incidence of chronic postoperative pain at 3 months after the surgery. The secondary outcomes include the incidence of chronic postoperative pain at 6 months after the surgery; the effect of lidocaine on postoperative pain within the first 24 and 48 h; total amount of sufentanil administered during entire procedure and the number of PCA triggers within 48 h after surgery. RESULTS: Compared with the control group, the incidence of chronic pain at 3 months after the surgery was significantly lower (13 cases, 46.4% vs. 6 cases, 20.7%, p < 0.05), but no significant difference at 6 months between two group. The cumulative dosage of sufentanil in perioperative period was significantly lower (149.64 ± 18.20 µg vs. 139.47 ± 16.75 µg) (p < 0.05), and the number of PCA triggers (8.21 ± 4.37 vs. 5.83 ± 4.12, p < 0.05) was significantly greater in the control group. The NRS pain scores at 24 h (1.68 ± 0.72 vs. 1.90 ± 0.86) and 48 h (1.21 ± 0.42 vs. 1.20 ± 0.41) after the operation were no significant difference. CONCLUSION: Perioperative infusion lidocaine significantly reduced the number of PCA triggers and the incidence of chronic postoperative pain at 3 months after the thoracoscopic radical pneumonectomy. TRIAL REGISTRATION: http://www.chictr.org.cn : ChiCTR1900024759, frist registration date 26/07/2019.

Association between ABO blood groups and postoperative pain in children after adenotonsillectomy: a prospective cohort study.

BACKGROUND: It has been known that ABO blood groups are linked to the phenotypes of certain diseases; however, and the relationship between ABO blood groups and postoperative pain have not been extensively studied, especially in children. This study was to investigate whether there would be an association between the four major ABO blood groups and postoperative pain, as indicated by the differences in pain scores and rescue fentanyl requirements among blood groups in children after adenotonsillectomy. METHODS: A total of 124 children, aged 3-7 years, ASA I or II, and undergoing elective adenotonsillectomy were enrolled in the study. Postoperative pain was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and the rescue fentanyl requirement in post anesthesia care unit (PACU) was analyzed. Pediatric Anesthesia Emergence Delirium (PAED) score and the duration of PACU were recorded. The postoperative nausea and vomiting (PONV) within 24 h were documented. RESULTS: Among four blood type groups, no significant differences were observed regarding surgery time, and the gaps of fentanyl given at the anesthesia induction and the first rescue fentanyl injection in PACU. However, patients from AB and B blood groups had significantly higher pain score at initial CHEOPS assessment and consequently, higher consumption of rescue fentanyl during PACU stay. A significantly higher percentage of patients had received > 1 µg/kg rescue fentanyl. Higher PAED scores were also observed in AB and B blood groups. CONCLUSION: Paediatric patients with AB and B blood type had higher postoperative CHEOPS pain score and required significantly more fentanyl for pain control than those with A and O blood type after T&A. The initial scores of PAED in patients with AB and B blood type were also higher than that in patients with A and O blood type.

Effect of intravenous administration of lidocaine on the ED50 of propofol induction dose during gastroscopy in adult patients: A randomized, controlled study.

WHAT IS KNOWN AND OBJECTIVE: Propofol provides a prominent sedation effect in gastroscopy. However, sedation with propofol alone during gastroscopy might result in circulatory and respiratory depression. This study aimed to test the hypothesis that the addition of intravenous lidocaine to propofol-based sedation could decrease the ED50 of propofol induction dose during gastroscopy in adult patients while the respiratory and haemodynamic stability were not compromised. METHODS: Patients undergoing gastroscopy were randomly enrolled into lidocaine + propofol (L + P) group or normal saline + propofol (NS + P) group. Subjects were initially administered intravenous bolus of 1.5 mg/kg lidocaine in L + P group or equivalent volume of 0.9% saline in NS + P group. Anaesthesia was then induced with a single bolus of 1.0 µg sufentanil followed by injection of propofol in all patients. The induction dose of propofol for each individual patient was determined by the protocol of Dixon "up-and-down" method for both groups. The primary end point was the ED50 of propofol induction dose. RESULTS: Totally, 48 patients were enrolled and completed this study. Compared with the NS + P group, the ED50 of propofol induction dose was significantly reduced in the L + P group (2.01 mg/kg vs. 1.69 mg/kg) (U = 61.5, p < 0.001). WHAT IS NEW AND CONCLUSION: The addition of intravenous lidocaine significantly reduced the ED50 of propofol induction dose during gastroscopy in adult patients. TRIAL REGISTRATION: The present clinical trial was registered at http://www.chictr.org.cn/ (registration No. ChiCTR1900024025, 23 June 2019).

The association of the optimal bolus of dexmedetomidine with its favourable haemodynamic outcomes in adult surgical patients under general anaesthesia.

AIMS: Dexmedetomidine is highly specific α2-adrenoceptor agonist. A single bolus of dexmedetomidine can achieve clinical therapeutic effect. Therefore, it is essential to know the safety margin between the clinical effectiveness dosages of dexmedetomidine and its side effect. METHODS: A total of 42 patients who underwent elective thyroidectomy were enrolled in this study. Dexmedetomidine was given as a single bolus injection 30 min towards the end of surgery. The up-and-down sequential schedule was used in this study. The starting dose of dexmedetomidine was set at 0.1 µg/kg in the first patient and the next patient would then receive a dose of dexmedetomidine decremented by 0.05 µg/kg if the prior patient's baseline heart rate (HR) had a decrease of ≥20% and/or mean arterial blood pressure (MAP) increase or decrease of ≥20%, otherwise, the following patient would receive an incremental 0.05 µg/kg dose of dexmedetomidine. The analytic techniques of linear, linear-logarithmic, exponential regressions and centred isotonic regression were used to determine the ED50 of dexmedetomidine and the residual standard errors were calculated for the comparison of goodness of fit among the different models. RESULTS: The median (interquartile range [range]) lowest HR was 57 beats/min (53-63.3[46-76]) with an average HR decrease of 8.0 beats/min (5-13 [4 to 23]). The median (interquartile range [range]) highest MAP was 98 mmHg (91.8-105 [83-126]) with a MAP increase of 10.0 mmHg (6.8-18.0 [2-24]). The ED50 (95% confidence interval) from 4 different statistical approaches (linear, linear-logarithmic, exponential regressions and centred isotonic regression) were 0.262 µg/kg (0.243, 0.306), 0.252 µg/kg (0.238, 0.307), 0.283 µg/kg (0.238, 0.307), and 0.278 µg/kg, respectively. Among the 4 models, the exponential regression had the least residual standard error (0.03618). CONCLUSION: The ED50 derived from 4 statistical models for an intravenous bolus of dexmedetomidine without significant haemodynamic effects was distributed in a narrow range of 0.252-0.283 µg/kg, and the exponential regression was the model to best match the study data.

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 propofol-sparing effect of intravenous lidocaine in elderly patients undergoing colonoscopy: a randomized, double-blinded, controlled study.

BACKGROUND: Propofol provides a prominent sedation effect in colonoscopy. However, anesthesia and sedation induced with propofol in the elderly might result in cardiopulmonary complications, especially when it is combined with opoids in the regimen. This study aimed to test the hypothesis that the addition of intravenous lidocaine to propofol-based sedation could decrease the overall propofol requirement in elderly patients during colonoscopy while the procedural sedation satisfaction and the hemodynamic stability were not compromised. METHODS: Ninety-two patients undergoing colonoscopy were randomly enrolled into lidocaine+propofol (L + P) group or normal saline+propofol (NS + P) groups. Subjects received intravenous bolus of 1.5 mg/kg lidocaine followed by 4 mg kg- 1 h- 1 lidocaine continuous infusion in L + P group or equivalent volumes of normal saline for boluses and infusion in NS + P group. Anesthesia was induced with 2.5 µg sufentanil followed by injection of 1.2 mg kg- 1 propofol in all patients. A single supplemental bolus of 0.6 mg kg- 1 propofol was administered whenever MOAA/S score > 1 or had body movement during the colonoscopy. The recorded primary endpoints included: the total amount of propofol administered during entire procedure, the supplemental amount of propofol after induction, and the frequencies of boluses of supplemental propofol. RESULTS: A total of 79 patients were included in the final analysis. Compared with NS + P group, the total amounts of propofol (induction plus supplemental) were no significant differences in L + P group; however, the required supplemental propofol was less (69.9 ± 39.2 mg vs. 51.5 ± 38.6 mg) (P = 0.039); the average frequencies of boluses of supplemental propofol given after induction were lower (2.1 ± 1.1 vs. 1.4 ± 0.9) (P = 0.003); the calculated "unit propofol" infusion rate was lower (0.18 ± 0.05 vs. 0.14 ± 0.04 mg kg- 1 min- 1) (P = 0.002). CONCLUSIONS: The addition of intravenous lidocaine to propofol-based sedation resulted in a remarked reduction of supplemental propofol in the elderly during colonoscopy. TRIAL REGISTRATION: The present clinical trial was registered at http://www.chictr.org.cn on 11th March 2019 (registration No. ChiCTR1900021818).

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.

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.

Intravenous dexmedetomidine pre-medication reduces the required minimum alveolar concentration of sevoflurane for smooth tracheal extubation in anesthetized children: a randomized clinical trial.

BACKGROUND: It has been known that Dexmedetomidine pre-medication enhances the effects of volatile anesthetics, reduces the need of sevoflurane, and facilitates smooth extubation in anesthetized children. This present study was designed to determine the effects of different doses of intravenous dexmedetomidine pre-medication on minimum alveolar concentration of sevoflurane for smooth tracheal extubation (MACEX) in anesthetized children. METHODS: A total of seventy-five pediatric patients, aged 3-7 years, ASA physical status I and II, and undergoing tonsillectomy were randomized to receive intravenous saline (Group D0), dexmedetomidine 1 µg∙kg-1 (Group D1), or dexmedetomidine 2 µg∙kg-1 (Group D2) approximately 10 min before anesthesia start. Sevoflurane was used for anesthesia induction and anesthesia maintenance. At the end of surgery, the initial concentration of sevoflurane for smooth tracheal extubation was determined according to the modified Dixon's "up-and-down" method. The starting sevoflurane for the first patient was 1.5% in Group D0, 1.0% in Group D1, and 0.8% in Group D2, with subsequent 0.1% up or down in next patient based on whether smooth extubation had been achieved or not in current patient. The endotreacheal tube was removed after the predetermined concentration had been maintained constant for ten minutes. All responses ("smooth" or "not smooth") to tracheal extubation and respiratory complications were assessed. RESULTS: MACEX values of sevoflurane in Group D2 (0.51 ± 0.13%) was significantly lower than in Group D1 (0.83 ± 0.10%; P < 0.001), the latter being significantly lower than in Group D0 (1.40 ± 0.12%; P < 0.001). EC95 values of sevoflurane were 0.83%, 1.07%, and 1.73% in Group D2, Group D1, and Group D0, respectively. No patient in the current study had laryngospasm. CONCLUSION: Dexmedetomidine decreased the required MACEX values of sevoflurane to achieve smooth extubation in a dose-dependent manner. Intravenous dexmedetomidine 1 µg∙kg-1 and 2 µg∙kg-1 pre-medication decreased MACEX by 41% and 64%, respectively. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-IOD-17011601 , date of registration: 09 Jun 2017, retrospectively registered.

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.

Genome-Wide Identification, Expression, and Functional Analysis of the Sugar Transporter Gene Family in Cassava (Manihot esculenta).

The sugar transporter (STP) gene family encodes monosaccharide transporters that contain 12 transmembrane domains and belong to the major facilitator superfamily. STP genes play critical roles in monosaccharide distribution and participate in diverse plant metabolic processes. To investigate the potential roles of STPs in cassava (Manihot esculenta) tuber root growth, genome-wide identification and expression and functional analyses of the STP gene family were performed in this study. A total of 20 MeSTP genes (MeSTP1-20) containing the Sugar_tr conserved motifs were identified from the cassava genome, which could be further classified into four distinct groups in the phylogenetic tree. The expression profiles of the MeSTP genes explored using RNA-seq data showed that most of the MeSTP genes exhibited tissue-specific expression, and 15 out of 20 MeSTP genes were mainly expressed in the early storage root of cassava. qRT-PCR analysis further confirmed that most of the MeSTPs displayed higher expression in roots after 30 and 40 days of growth, suggesting that these genes may be involved in the early growth of tuber roots. Although all the MeSTP proteins exhibited plasma membrane localization, variations in monosaccharide transport activity were found through a complementation analysis in a yeast (Saccharomyces cerevisiae) mutant, defective in monosaccharide uptake. Among them, MeSTP2, MeSTP15, and MeSTP19 were able to efficiently complement the uptake of five monosaccharides in the yeast mutant, while MeSTP3 and MeSTP16 only grew on medium containing galactose, suggesting that these two MeSTP proteins are transporters specific for galactose. This study provides significant insights into the potential functions of MeSTPs in early tuber root growth, which possibly involves the regulation of monosaccharide distribution.

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.

To Pretreat or Not to Pretreat: Prophylactic Anticholinergic Administration Before Dexmedetomidine in Pediatric Imaging.

BACKGROUND: Dexmedetomidine (Dex) appears to be very effective as a sole sedative for pediatric imaging when used at high doses, but at an increased risk of transient hypertension, hypotension, and bradycardia. There are no clinical evidence/guidelines to guide anesthesia providers as to whether patients should be pretreated with an anticholinergic. The aim of this study was to demonstrate the changes in hemodynamic parameters after Dex sedation attributed to receiving or not receiving an anticholinergic pretreatment and compare for any differences or similarities. A subgroups analysis was performed in children with Down syndrome (DS). METHODS: In this retrospective descriptive study, we reviewed the records of 163 children receiving Dex anesthesia during MRI studies. Data analyzed included demographics, history of DS, and hemodynamics (heart rate [HR], systolic blood pressure [SBP], and diastolic blood pressure [DBP]) following Dex loading and infusion and the administration of an anticholinergic (atropine or glycopyrrolate). RESULTS: The mean age was 94.5 months, and 52 (32%) patients had DS. The generalized linear mixed-effects regression model showed a significant reduction in HR and SBP in all patients when no anticholinergic was administered compared with when it was administered. There was no significant change with DBP. During the scan period, the HR of the no-anticholinergic group decreased 26.6%, whereas that of the anticholinergic group decreased by only 16.7% from baseline (P < 0.01). The maximal SBP increased by a significantly greater percentage, compared with baseline, in the anticholinergic group in comparison with the no-anticholinergic group (20.2% vs 10.4%, respectively; P = 0.02). In the DS group, the difference in the maximal SBP change during the scan period was exaggerated, with a percentage increase that was 36 times larger in the anticholinergic group compared with the no-anticholinergic group (22% vs 0.6%, respectively; P< 0.01). CONCLUSIONS: Administration of a prophylactic anticholinergic with Dex shows no advantage other than a transient clinically insignificant increase in HR and SBP, and it may precipitate transient exaggerated SBP in more patients compared with not using a prophylactic anticholinergic.

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.