Comparative study of biomarkers for the early identification of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in infectious mononucleosis.

BACKGROUND AND AIM: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. METHODS: We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. RESULTS: Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 µg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. CONCLUSIONS: IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.

Baicalein exerts anxiolytic and antinociceptive effects in a mouse model of posttraumatic stress disorder: Involvement of the serotonergic system and spinal delta-opioid receptors.

Post-traumatic stress disorder (PTSD) is a serious mental disease featured by a stress dysfunction that occurs after an individual has faced intense mental stress, often accompanied by anxiety and chronic pain. Currently, the mainstream drug for PTSD is serotonin reuptake inhibitors (SSRIs), however, their pain management for patients is limited. Baicalein, a Chinese traditional herbal medicine, has shown promising results in treating anxiety, depression, and pain. In this study, we found that baicalein may alleviate single prolonged stress (SPS)-induced PTSD-like behaviors in mice without altering baseline nociceptive sensitivity or activity. Meanwhile, baicalein increased the noradrenaline (NE) and serotonin (5-HT) content and decreased the ratio of 5-hydroxyindoleacetic acid (5-HIAA)/5-HT by inhibiting the activity of monoamine oxidase A (MAO-A) in SPS-induce mice. The anxiolytic and antinociceptive effects induced by baicalein were totally abolished by 5-HT depleting agents. Moreover, the anxiolytic effects of baicalein could be abolished by the 5-HT1A receptor antagonist WAY-100635, and the analgesic effects could be abolished by delta-opioid receptor antagonists in the spinal. Taken together, our study provides compelling evidence that baicalein reversed anxiety-like behaviors and neuropathic pain in PTSD through serotonergic system and spinal delta-opioid receptors.

Inhibition of Phosphodiesterase 2 Ameliorates Post-Traumatic Stress-Induced Alcohol Intake Disorder by Regulating cAMP/cGMP Signaling.

BACKGROUND: Post-traumatic stress disorder (PTSD) is the prevalent psychiatric disorder that induces alcohol use disorders (AUD) such as abnormal alcohol intake and anxiety. However, little is known about whether phosphodiesterase 2 (PDE2)-cAMP/cGMP signaling is involved in PTSD-induced AUD. METHODS: The present study used single-prolonged stress (SPS) to mimic PTSD that induced increases in ethanol intake and preference (2-bottle choice test) and anxiety-like behavior (elevated-plus maze test and novelty suppressed feeding test). PDE2 inhibitor Bay 60-7550 (Bay) was administered to the mice and protein kinase A (PKA) inhibitor H89 and PKG inhibitor KT5823 were micro-injected into dorsolateral striatum (DLS) and central amygdala (CA) of mice to determine whether the effects of Bay on anxiety-like behavior in SPS mice are brain region dependent. RESULTS: PDE2 inhibitor Bay rescued SPS-induced decreases in open arm entries and open arm time exposure in elevated-plus maze test and reversed increased latency to feed in the novelty suppressed feeding test. Moreover, SPS-induced ethanol use disorder was reversed by Bay as evidenced by decreased ethanol intake and preference without changing total fluid intake in the SPS mice after treatment with Bay. However, Bay did not change the ethanol metabolism or sucrose or quinine intake and preference. The locomotor activity was not affected after treatment with Bay. Interestingly, microinjection of PKA or PKG inhibitor H89 or KT5823 into DLS prevented the effects of Bay on alcohol intake and preference and cAMP-response element binding proteins phosphorylation and brain derived neurotrophic factor expression in DLS but not on the anxiety-like behavior in SPS mice. Microinjection of these inhibitors into CA prevented Bay-induced anxiolytic-like effects and cAMP-response element binding proteins phosphorylation and brain derived neurotrophic factor levels in CA but did not affect ethanol intake in SPS mice, indicating that the effects of Bay on different behaviors are brain region dependent. CONCLUSIONS: These findings support the hypothesis that PDE2-cAMP/cGMP signaling may differentially mediate PTSD-induced AUD and anxiety-like behavior.

The Current State of the Art in PARP Inhibitor-Based Delivery Nanosystems.

Poly (adenosine diphosphate [ADP]-ribose) polymerases inhibitors (PARPi), the first clinically approved drug that exhibits synthetic lethality, are moving to the forefront of cancer treatments. Currently, the oral bioavailability of PARPi is quite low; thus, it is a major challenge to effectively and safely deliver PARPi during clinical cancer therapy. Nanotechnology has greatly advanced the development of drug delivery. Based on the basic characteristics and various forms of nanoparticles, drug delivery systems can prolong the time that drugs circulate, realize the controlled release of drugs, provide drugs with an active targeting ability, and spatiotemporally present combination treatment. Furthermore, nanosystems may not only enhance drug efficiency but also reduce adverse side effects. This review focuses on strategies involving nanoparticle-based delivery for PARPi, including single administration and codelivery with other agents. We believe that nanosystems have great potential in advancing PARPi efficacy for cancer therapy.

Conjoint Fascial Sheath Suspension for Severe Blepharoptosis through Palpebral Margin Incision.

BACKGROUND: Conjoint fascial sheath suspension can achieve pleasing surgical efficacy and dynamic eyelid movement in the treatment of severe ptosis. In recent years, the palpebral margin incision technique has been applied for double-eyelid blepharoplasty, which is characterized by inconspicuous scarring, short convalescence, and natural-looking outcome. However, studies of the application of this technique in the treatment of ptosis are scarce. This article aims to evaluate the efficacy and safety of conjoint fascial sheath suspension for treating severe blepharoptosis through palpebral margin incision. METHODS: From March 2019 to January 2021, 32 patients (37 eyelids) underwent treatment with the modified technique. Preoperatively, levator muscle function and margin reflex distance 1 were documented. Correction effects, symmetry results, and complications were also evaluated postoperatively. RESULTS: Adequate or normal correction was achieved in 33 eyelids (89.2%), and 31 patients (96.9%) obtained good or fair symmetry results. Common complications were undercorrection and conjunctival prolapse, which were both observed in four eyelids (10.8%), followed by overcorrection and hematoma. CONCLUSIONS: The modified technique provides physical eyelid elevation and inconspicuous scarring and is effective for treating severe ptosis. Satisfactory functional and esthetic results could be obtained simultaneously without severe complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Impact of arabinoxylan on characteristics, stability and lipid oxidation of oil-in-water emulsions: Arabinoxylan from wheat bran, corn bran, rice bran, and rye bran.

To investigate the impact of arabinoxylan (AX) on the physical and oxidative stability of oil-in-water emulsions, AX from wheat bran, corn bran, rice bran, or rye bran was incorporated into the production of whey protein isolate-stabilised emulsions. Decreased interfacial charge and increased mean particle diameters were recorded in all fresh emulsions with 0.1%-0.5% AX, as recorded by the ζ-potential and particle size measurement, indicating the adsorption of AX onto the oil droplets. No phase separation was observed in all emulsions with ≤0.3% AX after 14-day storage in dark. Spectrophotometric analysis demonstrated that all AX lowered the peroxide value and thiobarbituric acid reactive substance concentration in emulsions, with AX from rice bran being slightly more effective. Consequently, AX has the potential to be used as a natural interfacial antioxidant in emulsions, and the antioxidant capacity of AX varies with its source.

A viscoelastic PEGylated poly(glycerol sebacate)-based bilayer scaffold for cartilage regeneration in full-thickness osteochondral defect.

Defects of either articular cartilage or subchondral bone would destroy the structural integrity and functionality of the joint. Reconstruction of osteochondral defects requires difunctional scaffolds that simultaneously induce cartilage and subchondral bone morphogenesis, however, high-performance cartilage reconstructive scaffolds remain a considerable challenge. In this study, a solvent-free urethane crosslinking and spontaneous pore-forming procedure under room temperature was proposed and optimized to produce PEGylated poly(glycerol sebacate) (PEGS) scaffolds with controllable crosslinking degrees and hierarchical macro-/micro-porosities. Based on the economical and feasible preparative approach, the viscoelastic PEGS-12h with low crosslinking degree was demonstrated to significantly stimulate chondrogenic differentiation, maintain chondrocyte phenotype and enhance cartilage matrix secretion compared to elastic polymer with high crosslinking degree, emphasizing the importance of matrix viscoelasticity in cartilage regeneration. On this basis, the viscoelastic low-crosslinked PEGS-12h was combined with the well-acknowledged osteoinductive mesoporous bioactive glass (MBG) to construct a difunctional PEGS/MBG bilayer scaffold, and evaluated in a full-thickness osteochondral defect model in vivo. The PEGS/MBG bilayer scaffold successfully reconstructed well-integrated articular hyaline cartilage and its subchondral bone in 12 weeks, exhibiting extraordinary regenerative efficiency. The results indicated that the viscoelastic PEGS scaffold and PEGS/MBG bilayer scaffold proposed in this study made an excellent candidate for cartilage and osteochondral regeneration, and was expected for clinical translation in the future.

MBG scaffolds containing chitosan microspheres for binary delivery of IL-8 and BMP-2 for bone regeneration.

Biomimetic delivery of chemokines and growth factors based on stem cell recruitment and endochondral ossification, as the key steps in natural regenerative process, has been an area of intense research in recent years. An inflammatory chemokine, interleukin-8 (IL-8), was recently reported with high recruitment efficiency of bone marrow stem cells, chondrogenic inductivity and immune regulatory functions. In this study, the effect of IL-8 action duration on bone morphogenetic protein-2 (BMP-2)-induced bone regeneration was studied to achieve an optimal synergism of these two proteins. Herein, a mesoporous bioactive glass (MBG)-based scaffold with BMP-2 entrapment and IL-8-loaded chitosan microspheres (CMs) was developed. The MBG scaffold with size-matched mesopores was adopted for the long-term sustained delivery of BMP-2; and CMs with different sizes, prepared using a modified ionotropic gelation method, were customized to match the optimal action time of IL-8. The results indicated that CMs of 100 µm diameter and medium crosslinking density exhibited an 85% release of IL-8 in 7 days and the MBG substrate exhibited a long-term sustained release of BMP-2. Furthermore, the binary delivery system exhibited excellent biocompatibility and synergistically enhanced osteoinductivity. In an in situ bone regeneration model of a rabbit radius large segmental defect, the system efficiently accelerated the whole regenerative process, with the highest bone formation amount from an early stage and the highest degree of regenerative completion. Since delivery systems for multiple cytokines have been in great demand due to the requirement of complicated biological processes, we believe that this new binary delivery system could be customized to design other dual delivery systems for improving bone-repairing biomaterials with higher regenerative efficiency.

Lasing behavior modulation for ZnO whispering-gallery microcavities.

Four configurations of whispering-gallery-mode (WGM) microcavities were designed and fabricated to modulate the optically pumped lasing characteristics by polymer modification on hexagonal ZnO microrod surfaces. On the basis of the total internal reflection (TIR) at the boundary of microcavities, the lasing characteristics were improved by raising the relative refractive index. Considering the different reflective conditions at various side surfaces, the typical lasing mode equation for whispering-gallery microcavity was modified to adapt for general situation even with unsymmetrical structure, and then employed to discuss the observed lasing behaviors, in the polyvinylcarbazole (PVK) modified ZnO microrods, such as mode position, mode numbers and quality factor. The optical field distributions for TE modes of the four configurations were also simulated by 2-dimensional finite difference time-domain (FDTD) method. The simulation agreed well with the experimental results to support the resonance mechanism.

Optical properties of a planar metamaterial with chiral symmetry breaking.

The optical properties of a planar metamaterial with gammadion-shaped chiral symmetry breaking holes array have been investigated both theoretically and experimentally. The results indicate that the introduction of the chiral symmetry breaking causes the split of the transmission peak and exerts large influence on the optical rotation and circular dichroism. Our metamaterials might have potential applications in future design of plasmonic devices.