[The characteristics of neutrophil extracellular traps produced by all-trans retinoic acid-induced dHL-60 under PMA stimulation].

Extracellular traps released by neutrophils (neutrophil extracellular traps, NETs) are a double-edged sword, and understanding the mechanism of NET formation is of great significance for disease treatment. However, the short lifespan, the large individual differences, and the inability to perform gene editing render it difficult to decipher NET formation using neutrophils. It is necessary to find a model cell to replace neutrophils to study the mechanism of NET formation. In this study, we used different concentrations (0, 0.1, 1, and 10 µmol/L) of all-trans retinoic acid (ATRA) to differentiate HL-60 cells for different days (1, 3, 5, and 7 days). By detecting the cell viability and nuclear morphology of cells, we confirmed that HL-60 cells were differentiated to neutrophil-like cells (dHL-60) after treated with ATRA for at least 5 days. Using immunofluorescence staining to detect the formation of NETs, we demonstrated that dHL-60 cells differentiated for 5 days with 1 µmol/L ATRA could generate NETs comparable to those produced by neutrophils upon phorbol 12-myristate 13-acetate (PMA) stimulation, without histone H3 citrullination. Furthermore, the formation of NETs by dHL-60 cells were NADPH-dependent and PAD4-independent, consistent with neutrophils. Taken together, these observations suggest that dHL-60 cells differentiated with 1 µmol/L ATRA for 5 days can be used as a model cell for neutrophils to study the mechanism of NET formation.

Wnt10a/ß-catenin signalling is involved in kindlin-1-mediated astrocyte activation in a chronic construction injury rat model.

The activation of spinal astrocytes and release of neuroinflammatory mediators are important events in neuropathic pain (NP) pathogenesis. In this study, we investigated the role of Wnt10a/ß-catenin signalling in kindlin-1-mediated astrocyte activation using a chronic constriction injury (CCI) NP rat model. Using kindlin-1 overexpression and knockdown plasmids, we assessed hyperalgesia, changes in spinal astrocyte activation and the release of inflammatory mediators in a NP rat model. We also performed coimmunoprecipitation, Western blotting and real-time polymerase chain reaction (PCR) to characterize the underlying mechanisms of kindlin-1 in astrocyte cultures in vitro. Kindlin-1 was significantly upregulated in CCI rats and promoted hyperalgesia. Moreover, we observed increased kindlin-1, Wnt10a and glial fibrillary acidic protein (GFAP; biomarker for astroglial injury) levels and the release of inflammatory mediators in NP rats (p < 0.05). Inhibiting GFAP in vitro led to decreased kindlin-1 levels, prevented astrocyte activation, decreased Wnt10a level and the release of inflammatory mediators (p < 0.05). Coimmunoprecipitation showed that kindlin-1 can interact with Wnt10a. We showed that kindlin-1-mediated astrocyte activation was associated with Wnt10a/ß-catenin signalling and the downstream release of inflammatory mediators in a CCI NP rat model. Our findings provide novel insights into the molecular mechanisms of kindlin-1-mediated astrocyte activation after CCI.

Time- and dose-dependent correlations between patient-controlled epidural analgesia and intrapartum maternal fever.

BACKGROUND: To investigate the relationship between intrapartum maternal fever and the duration and dosage of patient-controlled epidural analgesia (PCEA). METHODS: This observational study included 159 pregnant women who voluntarily accepted PCEA. During labor, patients with body temperature ≥ 38 °C were classified into the Fever group, (n = 42), and those with body temperature < 38 °C were classified into the No-fever group (n = 117). The outcome measures included the duration of PCEA, number of PCEA, and total PCEA amount. Body temperature and parturient variables, including interpartum fever status and the duration of any fever were monitored. RESULTS: The total PCEA duration and total PCEA amount in the Fever group were significantly higher than the corresponding values in the No-fever group (both, p < 0.05). The duration of fever was weakly correlated with the duration of PCEA (R2 = 0.08) and the total PCEA amount (R2 = 0.05) (both, p < 0.05). The total and effective PCEA were higher in the Fever group than in the No-fever group (both, p < 0.05). The total PCEA duration and total PCEA amount were positively correlated with the incidence of fever (both, p < 0.05). The diagnostic cutoff value for fever was 383 min, with a sensitivity of 78.6% and specificity of 57.3%. The mean temperature-time curves showed that parturients who developed fever had a steeper rise in temperature. CONCLUSIONS: This study showed that there were weak time- and dose-dependent correlations between PCEA and maternal fever during delivery. A total PCEA duration exceeding 6.3 h was associated with an increase in the duration of maternal intrapartum fever.

Effectiveness of analgesia with hydromorphone hydrochloride for postoperative pain following surgical repair of structural congenital malformations in children: a randomized controlled trial.

BACKGROUND: Effective postoperative analgesia is needed to prevent the negative effects of postoperative pain on patient outcomes. To compare the effectiveness of hydromorphone hydrochloride and sufentanil, combined with flurbiprofen axetil, for postoperative analgesia in pediatric patients. METHODS: This prospective randomized controlled trial included 222 pediatric patients scheduled for repair of a structural congenital malformation under general anesthesia. Patients were randomized into 3 groups: hydromorphone hydrochloride 0.1 mg/kg (H1), hydromorphone hydrochloride 0.2 mg/kg; (H2) or sufentanil 1.5 µg/kg (S). Analgesics were diluted in 0.9% saline to 100 ml and infused continuously at a basic flow rate of 2 mL per h. The primary outcome measure was the Face, Legs, Activity, Cry, and Consolability (FLACC) pain score. Secondary outcomes included heart rate (HR), respiration rate (RR), SpO2, Ramsay sedation scores, scores on the Paediatric Anaesthesia Emergence Delirium (PAED) scale, adverse reactions, parent satisfaction with analgesia. RESULTS: The FLACC score was significantly lower in H1 and H2 groups compared to S. The Ramsay sedation score was significantly higher in H1 and H2 groups compared to S. Recovery time was shorter in H1 group compared to patients H2 group or S group. There were no significant differences in the PAED scale, HR, RR, SpO2, adverse reactions, satisfaction of parents with analgesia, or length and cost of hospital stay. CONCLUSIONS: Hydromorphone hydrochloride is a more effective analgesic than sufentanil for postoperative pain in pediatric patients following surgical repair of a structural congenital malformation, however, hydromorphone hydrochloride and sufentanil had similar safety profiles in this patient population. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-INR-17013935). Clinical trial registry URL: Date of registration: December 14, 2017.

[LPS stimulating neutrophils firmly adhered to ICAM-1 to form extracellular traps depends on integrin Mac-1 and cytoskeletal proteins].

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither ß2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.

Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway.

Context: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle.Objective: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism.Materials and methods: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25-80 µg/mL cisplatin and/or 5-80 µM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA.Results: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 µg/mL NB and 40 µg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner.Discussion and conclusions: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic.

Kindlin-1 is a key protein in hyperbaric oxygen therapy for the treatment of neuropathic pain.

Background: Hyperbaric oxygen therapy is increasingly used in adjuvant therapies to treat neuropathic pain. However, the specific targets of hyperbaric oxygen treatment in neuropathic pain remain unclear. Recently, we found that hyperbaric oxygen therapy produces an antinociceptive response via the kindlin-1/wnt-10a signaling pathway in a chronic pain injury model in rats. Methods: The rats received an intraperitoneal injection of AAV-FERMT1 or an adeno-associated virus control vector 20 days before the chronic constriction injury operation. During five consecutive days of hyperbaric oxygen treatment, mechanical withdrawal threshold and thermal withdrawal latency tests were performed. Then, kindlin-1 expression was examined by real-time polymerase chain reaction and Western blot analysis. Meanwhile, the activation of glial cells and the production of TNF-α, IL-1ß, and fractalkine were also determined. Results: Our findings demonstrated that hyperbaric oxygen therapy inhibited the chronic constriction injury­induced increase in kindlin-1 expression. Furthermore, overexpression of kindlin-1 reversed the antinociceptive effects of hyperbaric oxygen therapy. The observed hyperbaric oxygen­induced reductions in glial cell activation and neuroinflammation, as indicated by the production of TNF-α, IL-1ß, and fractalkine, were also prominently diminished in the group with kindlin-1 overexpression. Conclusions: Our findings demonstrate that kindlin-1 is a key protein in the action of hyperbaric oxygen therapy in the treatment of neuropathic pain. Indeed, interference with kindlin-1 may be a drug target for reducing the neuroinflammatory responses of the glial population in neuropathic pain.

Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain. METHODS: Rats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and ß-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA. RESULTS: Our findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI). CONCLUSIONS: Our findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.

The NO-cGMP-PKG signal transduction pathway is involved in the analgesic effect of early hyperbaric oxygen treatment of neuropathic pain.

BACKGROUND: Hyperbaric oxygen (HBO) has the potential to relieve neuropathic pain. The purpose of this study was to determine whether the NO-cGMP-PKG signaling pathway is involved in the analgesic effects of early hyperbaric oxygen treatment of neuropathic pain in rats. METHODS: Rats were randomly grouped for establishment of chronic constriction injury (CCI) models. Intrathecal catheters were inserted and 2.5ATA HBO therapy was administered from day 1 post-surgery for 60 minutes daily, continuously for 5 days; menstruum NS, DMSO, NO synthase(NOS) nonspecific inhibitor (L-NAME), soluble guanylyl cyclase(sGC) inhibitor (ODQ) and protein kinase G(PKG) inhibitor (KT5823) were administered intrathecally 30 minutes prior to HBO therapy. Pain-related behaviors in rats were observed at specific time points. Western blot and real-time RT-PCR were used to observe the expressions of PKG1 mRNA and protein in the spinal dorsal horn. RESULTS: Compared with the CCI group, HBO could significantly relieve mechanical and thermal hyperalgesia in rats. After intrathecal administration of L-NAME, ODQ and KT5823, effects of HBO on relieving hyperalgesia in rats were reversed (P < 0.05 vs. HBO), and expression of PKG1 mRNA and protein decreased in the spinal dorsal horn of the animals (P < 0.05 vs. HBO). CONCLUSIONS: Early HBO therapy could significantly improve symptoms of hyperalgesia of neuropathic pain in rats, possibly via activation of the NO-cGMP-PKG signaling transduction pathway.

Intrathecal Administration of Tempol Reduces Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Increasing SOD Activity and Inhibiting NGF Expression.

We investigate the antinociceptive effect of intrathecal and intraperitoneal tempol administration in a rat model of chronic constriction injury (CCI)-induced neuropathic pain and explore the underlying antinociceptive mechanisms of tempol. Rats were randomly assigned to four groups (n = 8 per group): sham group, CCI group, Tem1 group (intrathecal injection of tempol), and Tem2 group (intraperitoneal injection of tempol). Neuropathic pain was induced by CCI of the sciatic nerve. Tempol was intrathecally or intraperitoneally administered daily for 7 days beginning on postoperative day one. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. Structural changes were examined by hematoxylin and eosin staining, toluidine blue staining, and electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using the thiobarbituric acid and nitroblue tetrazolium methods, respectively. Nerve growth factor (NGF) expression levels were determined by immunohistochemistry and Western blot. Intrathecal, but not intraperitoneal, injection of tempol produced a persistent antinociceptive effect. Intraperitoneal injection of tempol did not result in high enough concentration of tempol in the cerebrospinal fluid. Intrathecal, but not intraperitoneal, injection of tempol inhibited CCI-induced structural damage in the spinal cord reduced MDA levels, and increased SOD activities in the spinal cord. Furthermore, intrathecal, but not intraperitoneal, injection of tempol further downregulated the expression of NGF in the spinal cord following CCI, and this effect was blocked by p38MAPK inhibitor. Intrathecal injection of tempol produces antinociceptive effects and reduces CCI-induced structural damage in the spinal cord by increasing SOD activities and downregulating the expression of NGF via the p38MAPK pathway. Intraperitoneal administration of tempol does not exhibit antinociceptive effects.

Cooling treatment on the reduction of category II fetal tracings.

OBJECTIVES: Epidural-related maternal fever increases the incidence of Category II fetal tracings. To compare the effectiveness of low-flow oxygen inhalation and cooling treatment for parturients with Category II fetal tracings caused by epidural-related maternal fever. METHODS: We investigated 200 pregnant women who accepted epidural analgesia during labor and had body temperature exceeding 38 °C during labor. Among the patients, 99 and 101 were randomly allocated to receive cooling treatment group (control group) and oxygen inhalation (oxygen group), respectively. The primary outcome was the incidence of Category II fetal heart rate tracings. RESULTS: The incidence of Category II fetal heart rate tracings in the control group was significantly higher than that in the oxygen group. However, no significant differences were noted between the two groups in terms of the Apgar scores; amniotic fluid turbidity; or maternal outcomes, including cesarean section rate, forceps delivery rate, lateral resection rate, manual removal of placenta rate, the amount of intrapartum hemorrhage, and hemorrhage at postpartum 2 h. Oxygen inhalation therapy was more effective than cooling treatment in reducing the incidence of Category II tracings. CONCLUSION: Low-flow and short-term oxygen inhalation for parturients with epidural-related maternal fever reduces the incidence of Category II fetal heart rate tracings, but had no significant influence on the mode of delivery or neonatal outcomes.

Biodegradable magnesium and zinc composite microspheres with synergistic osteogenic effect for enhanced bone regeneration.

Biodegradable polymer microspheres in bone tissue engineering have become appealing as their non-invasive advantages in irregular damage bone repair. However, current microspheres used in BTE still lack sufficient osteogenic capacity to induce effective bone regeneration. In this study, we developed osteogenic composite microspheres concurrently loaded with magnesium oxide (MgO) and zinc oxide (ZnO), both of which are osteogenic active substances, using a facile and scalable emulsification method. The osteogenic composite microspheres exhibited a sequential yet complementary release profile characterized by a rapid release of Mg2+ and a gradual release of Zn2+ in a physiological environment, thereby maintaining the concentration of bioactive ions at a sustained high level. As a result, the combination of Mg2+ and Zn2+ in the composite microspheres led to a synergistic enhancement in biomimetic mineralization and the upregulation in the expression of osteogenic-related genes and proteins at the cellular level. Through a critical-sized calvarial rate defect model, the osteogenic composite microspheres were demonstrated to have strong osteogenic ability to promote new bone formation via ultrasonic imaging, histological and immunohistochemical evaluations. In sum, these osteogenic composite microspheres as microcarriers of Mg2+ and Zn2+ have great potential in the delivery of therapeutic ions for treating bone defects.

The relationship between epidural analgesia and intrapartum maternal fever and the consequences for maternal and neonatal outcomes: a prospective observational study.

AIM: To use continuous real-time monitoring of maternal core body temperature during labor and investigate the association between epidural analgesia, intrapartum maternal fever, and maternal and neonatal outcomes. METHODS: Among 201 pregnant women attending our institution for a vaginal in-hospital delivery, 159 women received epidural analgesia and 42 women did not receive epidural analgesia. Women's core body temperature was continuously monitored for the duration of labor using a smartphone/iPad-connected wireless thermometer positioned in an axilla. The primary outcome was a change in maternal core body temperature during labor. Among women receiving epidural analgesia, maternal and neonatal outcomes were compared in women who developed an intrapartum fever and those who had no intrapartum temperature elevation. RESULTS: Of the women receiving epidural analgesia, 26.4% (n = 42/159) developed intrapartum fever ≥38 °C compared to 7.1% (n = 3/42) of women not receiving epidural analgesia. Among those receiving epidural analgesia, women who developed intrapartum fever had a significantly longer first stage of labor and a higher incidence of cesarean section, assisted vaginal delivery, intrapartum hemorrhage, and turbid amniotic fluid compared to women with no intrapartum temperature elevation. Neonates of women who developed intrapartum fever had lower 1- and 5-min Apgar scores compared to neonates of women with no intrapartum temperature elevation; however, the difference was not significant. CONCLUSION: This study used a precise and accurate method to monitor core body temperature among women receiving epidural analgesia. Results showed that the use of epidural analgesia during labor was associated with intrapartum maternal fever in all stages of labor. Fever after epidural analgesia was associated with adverse maternal outcomes, independent of neonatal complications.

Association between epidural-related maternal fever and short-and long-term prognosis of parturients: A prospective observational study.

We aimed to explore the association between epidural-related maternal fever (ERMF) and prognosis of parturients. 159 parturients who underwent vaginal delivery under labor epidural analgesia (LEA) received noninvasive continuous core body temperature monitoring. 122 of them completed the 42-day postpartum follow-up. Parturients with body temperature ≥38°C during labor were categorized as the Fever group, while the others were categorized as the No-Fever group. Compared to No-Fever group, Fever group had a greater proportion of primiparas, greater gestational age of parturients, and longer third stage of labor. The cesarean section and forceps delivery rates, and the amount of intrapartum hemorrhage in Fever group were significantly higher. There were no significant between-group differences with respect to puerperal infection, and amniotic fluid turbidity degree, neither significant between-group difference at 42-days postpartum. We found that ERMF was associated with some short-term outcomes. However, it showed no relation with long-term prognosis of the parturients at 42-days postpartum.

Mucosa-Like Conformal Hydrogel Coating for Aqueous Lubrication.

Mucosa is a protective and lubricating barrier in biological tissue, which has a great clinical inspiration because of its slippery, soft, and hydrophilic surface. However, mimicking mucosal traits on complex surface remains an enormous challenge. Herein, a novel approach to create mucosa-like conformal hydrogel coating is developed. A thin conformal hydrogel layer mimicking the epithelial layer is obtained by first absorbing micelles, followed by forming covalent interlinks with the polymer substrate via interface-initiated hydrogel polymerization. The resulting coating exhibits uniform thickness (≈15 µm), mucosa-matched compliance (Young's modulus = 1.1 ± 0.1 kPa) and lubrication (coefficients of friction = 0.018 ± 0.003), robust interfacial bonding against peeling (peeling strength = 1218.0 ± 187.9 J m-2 ), as well as high water absorption capacity. It effectively resists adhesion of proteins and bacteria without compromising biocompatibility. As demonstrated by an in vivo cynomolgus monkey model and clinical trial, applications of the mucosa-like conformal hydrogel coating on the endotracheal tube significantly reduce intubation-related complications, such as invasive stimuli, mucosal lesions, laryngeal edema, inflammation, and postoperative pain. This work offers a promising prototype for surface decoration of biomedical devices and holds great prospects for clinical translation to enable interventional operations with minimally invasive impacts.

Image-based deep learning in diagnosing the etiology of pneumonia on pediatric chest X-rays.

PURPOSE: Comparing the efficacy of a deep-learning model in classifying the etiology of pneumonia on pediatric chest X-rays (CXRs) with that of human readers. METHODS: We built a clinical-pediatric CXR set containing 4035 patients to exploit a deep-learning model called Resnet-50 for differentiating viral from bacterial pneumonia. The dataset was split into training (80%) and validation (20%). Model performance was assessed by receiver operating characteristic curve and area under the curve (AUC) on the first test set of 400 CXRs collected from different studies. For the second test set composed of 100 independent examinations obtained from the daily clinical practice at our institution, the kappa coefficient was selected to measure the interrater agreement in a pairwise fashion for the reference standard, all reviewers, and the model. Gradient-weighted class activation mapping was used to visualize the significant areas contributing to the model prediction. RESULTS: On the first test set, the best-performing classifier achieved an AUC of 0.919 (p < .001), with a sensitivity of 79.0% and specificity of 88.9%. On the second test set, the classifier achieved performance similar to that of human experts, which resulted in a sensitivity of 74.3% and specificity of 90.8%, positive and negative likelihood ratios of 8.1 and 0.3, respectively. Contingence tables and kappa values further revealed that expert reviewers and model reached substantial agreements on differentiating the etiology of pediatric pneumonia. CONCLUSIONS: This study demonstrated that the model performed similarly as human reviewers and recognized the regions of pathology on CXRs.

Highly improved aqueous lubrication of polymer surface by noncovalently bonding hyaluronic acid-based hydration layer for endotracheal intubation.

Hydration lubrication is the key responsible for the exceptionally low boundary friction between biosurfaces. However, it is a challenge to settle a hydration layer on a polymer surface via a noncovalent manner. Herein, we develop a highly lubricated coating absorbed onto the polymer surface via intermolecular association of hyaluronic acid (HA)-based micelles. A poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (Pluronic, F127) is recruited to complex with HA and further self-assembled to form a thick micelle layer. High water-retaining capacity of the HA/F127 coating enables the decorated surface with excellent hydrophilicity and boundary lubrication, where the coefficient of friction in aqueous media is reduced by 60% compared with the bare polymer surface. The HA/F127 coating suppresses nonspecific protein adsorption and exhibits good biocompatibility. More remarkably, an in vivo cynomolgus monkey model, demonstrates the utility of the HA/F127 coating in alleviating or preventing complications of endotracheal intubation, such as foreign irritation, airway mucosal damage, and inflammatory response. This cost-effective and scalable approach is suitable to manufacture interventional devices especially disposable medical devices with highly lubricated surface.

The effects of ropivacaine 0.0625% and levobupivacaine 0.0625% on uterine and abdominal muscle electromyographic activity during the second stage of labor.

BACKGROUND: This study investigated the effect of ropivacaine on uterine and abdominal muscle electromyographic activity during the second stage of labor. METHODS: A total of 161 patients, including 48 patients receiving 0.0625% ropivacaine for patient-controlled epidural analgesia (PCEA), 64 patients receiving 0.0625% levobupivacaine for PCEA, and 49 patients with no PCEA completed the study. Uterine and abdominal muscle electromyographic activity was continuously recorded from the abdominal surface during the second stage of labor. Maternal demographic and clinical characteristics, maternal and neonatal outcomes, and various electromyographic parameters were recorded. RESULTS: Second stage of labor was significantly prolonged (P=0.007) for levobupivacaine compared to ropivacaine or no PCEA. The root-mean-square and duration of uterine muscle electromyographic activity was significantly lower for levobupivacaine or ropivacaine compared to no PCEA. The root-mean-square and power of abdominal muscle electromyographic activity was significantly lower for levobupivacaine compared to ropivacaine or no PCEA; the peak frequency of abdominal muscle electromyographic activity was significantly higher for ropivacaine. Visual analogue scale pain scores in patients in the levobupivacaine group or ropivacaine group decreased significantly over time compared to patients in the no PCEA group. CONCLUSIONS: In conclusion 0.0625% ropivacaine does not suppress abdominal muscle electromyographic activity during the second stage of labor. Maternal and neonatal outcomes were similar in patients receiving ropivacaine or no PCEA.

Promoting osteoblast proliferation on polymer bone substitutes with bone-like structure by combining hydroxyapatite and bioactive glass.

Mimicking the structural features of natural bone has been demonstrated to bring pronounced advantages for mechanical reinforcement of polymeric orthopedic substitutes that are composed of bioinert polymer matrix and bioactive fillers. However, to trigger effective bone formation and implant integration, the bioactivity of bone substitutes plays a vital role. We hypothesized that the use of hydroxyapatite (HA) and bioactive glass (BG), compared to the use of HA alone, could improve the biological properties of polymer-based bone substitutes. Herein, high-density polyethylene (PE) composites loaded with HA and BG were fabricated using a modified injection molding machine that can provide intense shear flow to regulate the hierarchical structure of the composites. Morphological observation revealed that bone-like structures were formed in both HA/PE and BG/HA/PE composites, showing highly oriented interlocked shish kebabs. In addition, the bioactive fillers were distributed uniformly. Osteoblast proliferation was promoted by the combination of HA and BG. The mechanism was the upregulation of Runx2 expression (1.51 ±â€¯0.17) with BG and the activation of the TAZ/YAP (1.41/0.64) signaling pathway, which accelerated the generation of ossification-related proteins. BG can regulate microRNA to promote the mRNA expression of Runx2. The silencing of Runx2 expression can inhibit BG-induced osteoblast proliferation. These results suggest that the BG/HA/PE composites having a bone-like structure have high potential as bone substitutes to repair large bone defects.