Hydrophobization of Ribonucleic Acids for Facile Systemic Delivery and Multifaceted Cancer Immunotherapy.

Ribonucleic acids (RNAs) enable disease-related gene inhibition, expression, and editing and represent promising therapeutics in various diseases. The efficacy of RNA relies heavily on the presence of a secure and effective delivery system. Herein, we found that RNA could be hydrophobized by cationic lipid and ionizable lipid and conveniently coassemble with amphiphilic polymer to achieve micelle-like nanoparticles (MNP). The results of the study indicate that MNP exhibits a high level of efficiency in delivering RNA. Besides, the MNP encapsulating siRNA that targets CD47 and PD-L1 remarkably blocked these immune checkpoints in a melanoma tumor model and elicited a robust immune response. Moreover, the MNP encapsulating the mRNA of OVA achieved antigen translation and presentation, leading to an effective antitumor immunoprophylaxis outcome against OVA-expressing melanoma model. Our findings suggest that RNA hydrophobization could serve as a viable approach for delivering RNA, thereby facilitating the exploration of RNA therapy in disease treatment.

Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma.

Cholangiocarcinoma often remains undetected until advanced stages due to the lack of reliable diagnostic markers. Our goal was to identify a unique secretory protein for cholangiocarcinoma diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. We conducted bulk RNA-seq analysis to identify genes specifically upregulated in cholangiocarcinoma but not in most other cancers, benign hepatobiliary diseases, and chronic liver diseases focusing on exocrine protein-encoding genes. Single-cell RNA sequencing examined subcellular distribution. Immunohistochemistry and enzyme-linked immunosorbent assays assessed tissue and serum expression. Diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. Inter-alpha-trypsin inhibitor heavy chain family member five (ITIH5), a gene encoding an extracellular protein, is notably upregulated in cholangiocarcinoma. This elevation is not observed in most other cancer types, benign hepatobiliary diseases, or chronic liver disorders. It is specifically expressed by malignant cholangiocytes. ITIH5 expression in cholangiocarcinoma tissues exceeded that in nontumorous bile duct, hepatocellular carcinoma, and nontumorous hepatic tissues. Serum ITIH5 levels were elevated in cholangiocarcinoma compared with controls (hepatocellular carcinoma, benign diseases, chronic hepatitis B, and healthy individuals). ITIH5 yielded areas under the ROC curve (AUCs) from 0.839 to 0.851 distinguishing cholangiocarcinoma from controls. Combining ITIH5 with carbohydrate antigen 19-9 (CA19-9) enhanced CA19-9's diagnostic effectiveness. In conclusion, serum ITIH5 may serve as a novel noninvasive cholangiocarcinoma diagnostic marker.

Trust (in)congruence, open innovation, and circular economy performance: Polynomial regression and response surface analyses.

Engaging partner firms in open innovation is critical to overcoming internal resource/capability constraints to achieve firm and supply chain circular economy (CE) performance, yet scholars have not examined this link empirically. Further, while researchers have repeatedly emphasized trust as a key driver of open innovation performance, little is known from a dyadic trust perspective (e.g., congruence vs. incongruence, high-high congruence vs. low-low congruence). To fill these gaps, we propose a theoretical model based on the social exchange theory (SET) and test it using a dyadic dataset of listed Chinese manufacturing firms. The results suggest that 1) rather than unilateral trust from the focal firm or its partners, trust congruence is more predictive of successful open process and product innovations, 2) regarding congruence types (low-low vs. high-high), congruence at higher levels of trust facilitates open product innovation more than low-low trust congruence; interestingly, such an effect is not significant for open process innovation, 3) open process innovation has a positive influence on the focal firm's CE performance, but its impact on supply chain CE performance is not statistically significant, and 4) open product innovation has a significantly positive impact on the focal firm and supply chain CE performance. Our findings still hold after analyzing time-lagged models and alternative measurements as robustness checks. Our study provides meaningful theoretical contributions to the literature and useful, practical insights for managing inter-organizational relationships, open innovation, and CE performance.

Protective effect of quercetin on lung epithelial cell bystander-effect in the conditioned medium model of lung cancer metastasis induced by radiation.

To investigate the protective effect of Quercetin (Que) on lung epithelial cells (BEAS-2B) induced bystander effect (RIBE) after heavy ion irradiation of A549 cells. A549 cells were irradiated with 2 Gy X heavy ion rays to obtain a conditioned medium. BEAS-2B was incubated with a conditioned medium or Que. CCK-8 assay was used to screen the optimal effective concentration of Que and detect cell proliferation. Cell number was measured by cell counter and apoptosis rate was measured by flow cytometry. HMGB1 and ROS levels were measured by ELISA. Western blot was used to detect the protein expression of HMGB1, TLR4, p65, Bcl-2, Bax, Caspase3 and Cleaved Caspase3. The growth and proliferation rate of BEAS-2B decreased while the apoptosis rate increased after conditioned medium stimulation, and Que intervention inhibited this effect. The expression of HMGB1 and ROS increased after conditioned medium stimulation, and this effect was inhibited by Que intervention. In addition, the conditioned medium increased the levels of proteins of HMGB1, TLR4, p65, Bax, Caspase3 and Cleaved Caspase 3, and decreased levels of Bcl-2 protein, but Que intervention decreased the levels of HMGB1, TLR4, p65, Bax, Caspase3 and Cleaved Caspase 3proteins, and increased levels of Bcl-2 protein. The RIBE of BEAS-2B induced by irradiation of A549 is associated with HMGB1TLR4/NF-κB signaling pathway in conditioned medium inducing apoptosis by activating ROS, and Que may block RIBE-induced apoptosis by regulating HMGB1/TLR4/NF-κB pathway.

Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy with the second highest mortality and the third highest morbidity worldwide. However, the overall survival of patients is unsatisfactory, thus requiring more effective clinical strategies. Celastrol (CLT), a natural bioactive compound, has been reported to induce reactive oxygen species (ROS)-mediated apoptosis to exhibit significant antitumor effects against CRC. However, the poor water solubility, low targeting ability, and bioavailability of CLT have limited its application, and CLT-induced protective autophagy weakens its therapeutic efficiency. RESULTS: We designed a targeted chemo-phototherapy nanoplatform (HCR NPs) to improve the application of CLT. The codelivery of IR820 and CLT in HCR NPs solved the water-soluble problem of CLT and enhanced apoptosis via IR820-mediated hyperthermia. In addition, hydroxychloroquine (HCQ) conjugated to hyaluronic acid (HA) not only increased the active targeting of HCR NPs but also inhibited CLT-induced protective autophagy to exacerbate apoptosis, thus achieving an amplified antitumor effect. Importantly, the HCR NPs exhibited an excellent therapeutic effect on CRC both in vitro and in vivo. CONCLUSION: The HCR NPs presented in this study may not merely provide a new reference for the clinical application of CLT but also result in an attractive strategy for CRC treatment.

Hybrid DAER Based Cross-Modal Retrieval Exploiting Deep Representation Learning.

Information retrieval across multiple modes has attracted much attention from academics and practitioners. One key challenge of cross-modal retrieval is to eliminate the heterogeneous gap between different patterns. Most of the existing methods tend to jointly construct a common subspace. However, very little attention has been given to the study of the importance of different fine-grained regions of various modalities. This lack of consideration significantly influences the utilization of the extracted information of multiple modalities. Therefore, this study proposes a novel text-image cross-modal retrieval approach that constructs a dual attention network and an enhanced relation network (DAER). More specifically, the dual attention network tends to precisely extract fine-grained weight information from text and images, while the enhanced relation network is used to expand the differences between different categories of data in order to improve the computational accuracy of similarity. The comprehensive experimental results on three widely-used major datasets (i.e., Wikipedia, Pascal Sentence, and XMediaNet) show that our proposed approach is effective and superior to existing cross-modal retrieval methods.

Peripheral Nerve Denervation in Streptozotocin-Induced Diabetic Rats Is Reduced by Cilostazol.

Background and Objective: Our previous study demonstrated that consistent treatment of oral cilostazol was effective in reducing levels of painful peripheral neuropathy in streptozotocin-induced type I diabetic rats. As diabetic neuropathy is characterized by hyperglycemia-induced nerve damage in the periphery, this study aims to examine the neuropathology as well as the effects of cilostazol treatments on the integrity of peripheral small nerve fibers in type I diabetic rats. Materials and Methods: A total of ninety adult male Sprague-Dawley rats were divided into the following groups: (1) naïve (control) group; (2) diabetic rats (DM) group for 8 weeks; DM rats receiving either (3) 10 mg/kg oral cilostazol (Cilo10), (4) 30 mg/kg oral cilostazol (Cilo30), or (5) 100 mg/kg oral cilostazol (Cilo100) for 6 weeks. Pain tolerance thresholds of hind paws toward thermal and mechanical stimuli were assessed. Expressions of PGP9.5, P2X3, CGRP, and TRPV-1 targeting afferent nerve fibers in hind paw skin and glial cells in the spinal dorsal horn were examined via immunohistochemistry and immunofluorescence. Results: Oral cilostazol ameliorated the symptoms of mechanical allodynia but not thermal analgesia in DM rats. Significant reductions in PGP9.5-, P2X3-, CGRP, and TRPV-1-labeled penetrating nerve fibers in the epidermal layer indicated denervation of sensory nerves in the hind paw epidermis of DM rats. Denervation significantly improved in groups that received Cilo30 and Cilo100 in a dose-dependent manner. Cilostazol administration also suppressed microglial hyperactivation and increased astrocyte expressions in spinal dorsal horns. Conclusions: Oral cilostazol ameliorated hyperglycemia-induced peripheral small nerve fiber damage in the periphery of diabetic rats and effectively mitigated diabetic neuropathic pain via a central sensitization mechanism. Our findings present cilostazol not only as an effective option for managing symptoms of neuropathy but also for deterring the development of diabetic neuropathy in the early phase of type I diabetes.

[3+1+1+1] Annulation to the Pyridine Structure in Quinoline Molecules Based on DMSO as a Nonadjacent Dual-Methine Synthon: Simple Synthesis of 3-Arylquinolines from Arylaldehydes, Arylamines, and DMSO.

A [3+1+1+1] annulation of arylamines, arylaldehydes, and dimethyl sulfoxide (DMSO) to the pyridine structure in quinolines using DMSO as a nonadjacent dual-methine (═CH-) synthon is disclosed. In this annulation, arylamines provide two carbon atoms and one nitrogen atom, arylaldehydes furnish one carbon atom, and DMSO provides two nonadjacent methines (═CH-) to the pyridine ring in quinoline molecules. This annulation provides a simple approach for the synthesis of 3-arylquinolines from readily available substrates in useful yields. On the basis of the control experiments and the literature, a plausible mechanism is proposed.

Regioselective Synthetic Approach to Higher Alkenes from Lower Alkenes with Sulfoxides in the Fe3+/H2O2 System via Direct Alkylation or Arylation of the Csp2-H Bond on the C═C Bond of Alkenes.

The regioselective synthetic approach to higher alkenes from lower alkenes by using sulfoxides as alkyl or aryl reagents in the Fe3+/H2O2 system has been developed. This reaction realized direct alkylation or arylation of alkenes. In this reaction, sulfoxides afforded one Csp3 or Csp2 atom to the C═C bond of alkenes; one new Csp2-Csp3 bond or Csp2-Csp2 bond was formed. Nearly 40 products including di-, tri-, and tetra-substituted products were regioselectively synthesized. Both aliphatic and aromatic alkenes could participate in this reaction. Moreover, not only dimethyl sulfoxide but also three other sulfoxides can be applied to this reaction, including diethyl, dibenzyl, and diphenyl sulfoxide. The mechanism studies showed that this reaction may experience a coupling process via radical addition-elimination and the Fe3+/H2O2 system made the sulfoxides offered one alkyl or aryl radical to the C═C bond of alkenes.

Trachway® flexible stylet facilitates the correct placement of double-lumen endobronchial tube: a prospective, randomized study.

BACKGROUND: The mainstream facilitation of one-lung ventilation is using double-lumen endobronchial tubes. However, it is more difficult to be positioned properly and more likely to cause airway injuries. How to place double-lumen endobronchial tubes rapidly and correctly is important for thoracic anesthesiologists. METHODS: One hundred eight patients with an American Society of Anesthesiologists physical status of I to III were 20 years of age or over, and required one-lung ventilation for thoracic surgery. They were randomly assigned to the conventional technique group (n = 36), the flexible fiberoptic bronchoscopy group (n = 36), or the Trachway® flexible stylet group (n = 36). The primary endpoint was the time needed for intubation. T1, the time from the tip of the blade passing between the patient's lips to identification of the vocal cords; and T2, the time from identification of the vocal cords to the bronchial lumen was in the correct position. RESULTS: T1 had no significant difference between groups, but T2 was significantly shorter in the Trachway® flexible stylet group (p < 0.0001) and longer in the conventional technique group (p < 0.0001). CONCLUSIONS: Using Trachway® flexible stylet for correct placement of double-lumen endobronchial tubes not only significantly shortened the intubation time, but also reduced incidence of carinal injuries. It is an alternative, and a choice with good safety. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02364622, 18/02/2015, Retrospectively registered.

Persistent Postsurgical Pain in Oral Cancer Patients Reconstructed with Anterolateral Thigh Free Flap.

Background and Objectives: The anterolateral thigh (ALT) flap is widely used in head and neck reconstruction, but the postoperative thigh sensory function lacks sufficient evaluation. The present study reports the postsurgical pain and cancer-related quality of life (QoL) in different stages of oral cancer patients receiving anterolateral thigh (ALT) flap reconstruction. Materials and Methods: Patients were subgrouped into postoperative early-, mid-, and late-recovery stages (postoperative 0.5-1 years, 1-2 years, and above 2 years) according to the time point of assessment. The QoL was examined using the EORTC C-30. Postsurgical donor and receipt site pain was evaluated through subjective reports and sensory tests. Results: Ninety-four patients were included in the final analysis. The functional and global health-related QoL significantly improved with time after surgery. However, spontaneous pain was reported in 57.7%, 72.3%, and 42% of patients in early-, mid-, and late-recovery stages, mainly in donor sites rather than in receipt sites. The highest incidence of donor site pain after ALT flap reconstruction in oral cancer surgery was in the mid-recovery stage but remained high in the late-recovery stage (56.8% and 36.7%, respectively). Conclusions: The postsurgical pain in the donor site might persist to or exhibit delayed onset one to two years postoperatively but is much improved after postoperatively two years later. A longer postsurgical follow-up for over two years for pain and sensory dysfunction is indicated.

Unexpected Annulation between 2-Aminobenzyl Alcohols and Benzaldehydes in the Presence of DMSO: Regioselective Synthesis of Substituted Quinolines.

An unexpected annulation among 2-aminobenzyl alcohols, benzaldehydes, and DMSO to quinolines has been disclosed. For the reported annulation between 2-aminobenzyl alcohols and benzaldehydes, the change of the solvent from toluene to DMSO led to the change of the product from the diheteroatomic cyclic benzoxazines to monoheteroatomic cyclic quinolines. This annulation can be used to synthesize regioselectively different substituted quinolines by the choice of different 2-amino alcohols, aldehydes, and sulfoxides as substrates. Interestingly, introducing substituent groups to the α-position of sulfoxides resulted in the interchange of the positions between benzaldehydes and sulfoxides in the product quinolines. On the basis of the control experiments and literatures, a plausible mechanism for this annulation was proposed.

Two C═C Bond Participation in Annulation to Pyridines Based on DMF as the Nonadjacent N and C Atom Donors.

Two C═C bond participation in annulation to pyridines using N,N-dimethylformamide (DMF) as the N1 and C4 synthons has been carried out. In this reaction, DMF contributed one N atom and one C atom to two disconnected positions of pyridine ring, with no need for an additional nitrogen source. Two C═C bonds in two molecules of substituted styrenes offered four carbon atoms in the presence of iodine and persulfate. With the optimized conditions in hand, both symmetric and unsymmetric diaryl-substituted pyridines were obtained in useful yields. On the basis of relevant literature and a series of control experimental results, a possible mechanism was proposed in this work, which may demonstrate how DMF provides both N1 and C4 sources.

Comparison of laryngeal mask airway and endotracheal tube in preterm neonates receiving general anesthesia for inguinal hernia surgery: a retrospective study.

BACKGROUND: Preterm neonates are at higher risk of developing inguinal hernia, and have an increased risk of perioperative adverse events. Laryngeal mask airway (LMA) is claimed to be associated to decreasing perioperative respiratory complications compared to endotracheal tube (ETT) in infants under one year of age receiving minor surgery; thus, we conducted a retrospective survey in former preterm neonates below 5000 g to compare the respiratory complications between LMA and ETT in general anesthesia for inguinal hernia surgeries. METHODS: The inclusion criteria were: gestational age at birth under 37 weeks, body weight at surgery below 5000 g, and receiving scheduled inguinal hernia repair under general anesthesia with LMA or ETT. Infants who were dependent on mechanical ventilation preoperatively were excluded. The postoperative respiratory complications including delayed extubation, re-intubation, and apnea within postoperative 24 h were compared between groups. RESULTS: From July 2014 to December 2017, 72 neonates were enrolled into final analysis. There were 57 neonates managed with LMA, and only 15 neonates intubated with ETT during the study period. The gestational age at birth and post-menstrual age at surgery showed no significant difference between groups, although in the ETT group, the body weight at birth and at surgery were lower, and more infants had history of severe respiratory distress syndrome and had received oxygen therapy within two weeks prior to surgery. Surprisingly, none one of the infants developed delayed extubation, re-intubation, or postoperative apnea in the LMA group. In the ETT group, 40 percent of the neonates could not be successfully extubated in the operation theater. CONCLUSION: In preterm neonates, even in those younger than 52 weeks post-menstrual age who undergoing inguinal hernia repair in their early infancy, LMA appears feasible and safe as the airway device during general anesthesia in specific patient group. However, anesthesiologist might prefer ETT rather than LMA in some complex situation. In neonates with lower body weight at birth and at surgery, and with a history of severe RDS and oxygen-dependence, further prospective study is required.

A Preliminary Study of Adjunctive Nonconvulsive Electrotherapy for Treatment-Refractory Depression.

Nonconvulsive electrotherapy (NET) defined as electrical brain stimulation administered like standard electroconvulsive therapy (ECT), but below seizure threshold, could be effective for patients with treatment-refractory depression (TRD) with fewer adverse neurocognitive outcomes. However, there is a lack of studies in Chinese patients with TRD. Thus, this study was conducted to examine the efficacy and safety of adjunctive NET for Chinese patients with TRD. Twenty TRD patients were enrolled and underwent six NET treatments. Depressive symptoms, response, and remission were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 1, 3, and 6 NET treatments. Neurocognitive function was assessed by the Wisconsin Card Sorting Test (WCST) at baseline and after the completion of six NET treatments. Mean HAMD-17 scores declined significantly from 26.2 to 10.4 (p < 0.001) after post-NET. The rates of response and remission were 60.0% (95% CI: 36.5-83.5) and 10.0% (95% CI: 0-24.4), respectively. Neurocognitive performance improved following a course of NET. No significant association was found between changes in depressive symptoms and baseline neurocognitive function. Adjunctive NET appeared to be effective for patients with TRD, without adverse neurocognitive effects. Randomized controlled studies were warranted to confirm these findings.

Therapeutic effects and modulatory mechanism of Alpiniae oxyphyllae Fructus in chronic intermittent hypoxia induced enuresis in rats.

OBJECTIVE: The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)-induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE). METHODS: Female rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3-adrenergic receptor (ß3-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group. RESULTS: Compared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P2X3 receptor and muscarinic M3 receptor were expressed at higher levels, and ß3-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P2X3 receptor and muscarinic M3 receptor and increased the expression of the ß3-AR. CONCLUSIONS: AOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3 adrenergic receptor.

Association of T lymphocyte immune imbalance and IL-10 gene polymorphism with the risk of obstructive sleep apnea in children with obesity.

PURPOSE: The purpose of this study is to determine the role of T lymphocyte immune imbalance and interleukin (IL)-10 gene polymorphism in the development of obstructive sleep apnea (OSA) in obese children. METHODS: One hundred obese children at high-risk and low-risk for OSA based upon a sleep questionnaire were selected. Peripheral blood T lymphocyte subsets were measured by flow cytometry, and plasma IFN-γ, IL-4, and IL-10 cytokines were detected by ELISA. The relationships between OSA and the above variables were analyzed. IL-10 gene polymorphisms were analyzed by DNA sequencing. RESULTS: Ninety subjects completed all the tests. Forty-two patients were diagnosed as OSA by PSG. Compared with non-OSA children, the levels of CD4+ T cells, IFN-γ, and IL-4 were increased (P < 0.05) whereas the numbers of CD4+ CD25+ Treg and NKT cells and the levels of IL-10 were reduced (P < 0.05). Multiple linear regression analysis showed that IL-10 level was negatively associated with OAHI (OR 0.352, 95% CI 0.286-0.540; P < 0.05). In multivariate analysis, IL-10 also had a strong negative association with OSA after adjustment for confounding factors from models 1 to 3. Correlative analysis showed that IL-10 levels had a positive association with CD4+ CD25+ Treg (r = 0.628, P < 0.01). Furthermore, the IL-10/A-1082G gene polymorphism correlated with OSA. CONCLUSIONS: T lymphocyte immune imbalance was associated with OSA and IL-10 may play an important protective role in the pathogenesis of OSA in obese children.

Obesity in children with different risk factors for obstructive sleep apnea: a community-based study.

This study investigated the association between obesity and obstructive sleep apnea (OSA) in preschool and school-age children. Parents of obese and randomly chosen normal weight children completed a questionnaire on sleep-related symptoms, demography, family, and medical history. All subjects were invited to undergo polysomnography (PSG). OSA cases were defined as obstructive apnea hypopnea index (OAHI) ≥1. A total of 5930 children were studied with 9.5% obese (11.9% boys/6.1% girls), 205/2680 preschool and 360/3250 school children. There were 1030 children (535 obese/495 normal weight) who underwent PSG. OSA was higher in obese children and obese school children had higher OAHI, arousal index, and shorter total sleep time. However, there was no positive correlation between OSA and body mass index (BMI). The main risk factors for OSA in preschool children were adenotonsillar hypertrophy and recurrent respiratory tract infection. The main cause for OSA in school children was a history of parental snoring and obesity. Mallampati scores and sleep-related symptoms were found to be associated with OSA in both preschool and school children. CONCLUSION: We demonstrated differential risk factors for OSA in obese children, which suggest that a different mechanism may be involved in OSA development in preschool and school-age children. WHAT IS KNOWN: Various risk factors have been reported in obese children with OSA owing to the different age and different study design. Obese children have a higher prevalence and severity of obstructive sleep apnea (OSA). OSA risk factors in obese children are affected by different ages and study designs. WHAT IS NEW: A differential prevalence and risk factors for obese preschool and school-age children with OSA has been demonstrated.

[Role of the Notch signaling pathway in development of acute liver failure in a mouse model].

OBJECTIVE: To investigate the role of the Notch signaling pathway, and the underlying mechanism, in development of acute liver failure (ALF) in a mouse model. METHODS: For in vivo analysis of the role of Notch signaling in ALF, a mouse model of ALF was generated by intraperitoneal injection of 3.0 g/kg D-galactosamine. Histological specimens were stained by hematoxylin-eosin, and then studied microscopically.Expression level of Jaggedl, Notchl, NICD, and Hes5 was measured by western blotting (for protein) and real time-PCR (for mRNA). The level of CD68 protein was detected by immunohistochemical staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-10, high mobility group box 1 (HMGB1) chromatin protein, and lipopolysaccharide (LPS) were measured by standard methods. For in vitro analysis of the molecular mechanism, the RAW264.7 macrophage cell line was cultured with LPS in the absence or presence of the Notch inhibitor DAPT, and the intracellular levels of Notch1, NICD, and Hes5 were measured by western blotting and real time-PCR and the extracellular levels of IL-10 and HMGB1 were detected in the supematant. RESULTS: Compared with unmodeled (normal control) mice, the ALF modeled mice showed higher levels of serum ALT (848.40+/-94.83 U/L vs. 38.99+/-9.63 U/L), AST (911.49+/-67.65 U/L vs. 55.28+/-7.50 U/L), HMGB1 (101.91+/-12.43 µg/L vs. 20.73+/-5.37 µg/L), 1L-10 (4 627.88+/-842.45 pg/mL vs. 1 064.92+/-238.46 pg/mL) and LPS (11.80+/-0.89 EU/mL vs. 0.58+/-0.12 EU/mL), as well as higher expression of Jagged1 (mRNA: 7.63+/-1.41 vs. 1.00+/-0.00; protein: 0.71+/-0.07 vs. 0.34+/-0.07), Notch1 (mRNA: 7.10+/-0.66 vs. 1.00+/-0.00; protein: 0.66+/-0.11 vs. 0.27+/-0.08), NICD (protein: 0.76+/-0.08 vs. 0.27+/-0.08), Hes5 (mRNA: 7.95+/-0.71 vs. 1.00+/-0.00; protein: 1.20+/-0.07 vs. 0.76+/-0.07), and CD68 (protein: 7 685.05+/-417.34 vs. 2 294.01+/-392.93) (all P<0.01). In vitro, LPS increased the extracellular levels of HMGB1 (7.44+/-0.63 vs. 0.21+/-0.05), IL-10 (315.19+/-79.13 vs. 59.19+/-23.30) and the intracellular expression of Notch1 (mRNA: 6.49+/-0.73 vs. 1.00+/-0.00), NICD (protein: 0.65+/-0.10 vs. 0.23+/-0.07), and Hes5 (mRNA: 7.30+/-0.85 vs. 1.00+/-0.00; protein: 0.96+/-0.10 vs. 0.54+/-0.07) (all P<0.01). DAPT treatment led to a decrease above the index serum levels of HMGB1 (6.22+/-0.71) and IL-10 (252.06+/-57.63), and of expression of Notch 1 (mRNA: 3.20+/-0.68), NICD (protein: 0.42+/-0.05), and Hes5 (mRNA: 4.72+/-0.67; protein: 0.84+/-0.09) (P<0.01 or <0.05). CONCLUSION: The Notch signaling pathway may plan an important role in the development of ALF upon activation of the pathway in macrophages by LPS and leading to promoted secretion of HMGB 1 and IL-10, with a greater effect on the former.

[Control study on antimicrobial resistance of invasive and non-invasive Streptococcus pneumoniae in children].

OBJECTIVE: To investigate the antimicrobial resistance of invasive and non-invasive Streptococcus pneumoniae (SP) strains in children and to provide a basis for proper use of antimicrobial drugs in the treatment of SP infection. METHODS: Seventy children who were diagnosed with invasive pneumococcal diseases (IPD) between January 2009 and December 2013 were enrolled, and 164 children with lower respiratory tract infection caused by SP were randomly selected as the control group. The samples from sterile sites (blood, cerebrospinal fluid, etc) of children with IPD, as well as the sputum samples of children in the control group, were collected for bacterial culture, and the drug susceptibility tests for isolated SP strains were conducted. RESULTS: A total of 82 invasive strains of SP were isolated from sterile sites of 70 children with IPD; 49 strains (60%) were isolated from blood, and 19 strains (23%) from cerebrospinal fluid. The detection rate of invasive SP strains decreased from 2009 to 2013 (P<0.01). The total detection rates of penicillin-nonsusceptible SP from the invasive and non-invasive strains were 27% and 17% respectively (P>0.05). Among invasive strains, the penicillin-nonsusceptible SP strains had significantly higher rates of insusceptibility to cefotaxime, ceftriaxone, and cefepime than the penicillin-susceptible SP (P<0.01). There were significant differences in the rates of insusceptibility to cefotaxime, ceftriaxone, and meropenem between the sensitive and non-sensitive SP strains (P<0.05). The multidrug resistance rates of the invasive and non-invasive SP strains were 89% and 93% respectively (P>0.05). CONCLUSIONS: Invasive SP can easily invade the blood in children, but the total detection rate has decreased year by year. The results of drug sensitivity tests have guiding significance for proper use of antimicrobial drugs for different SP infections.