Baseline Severity and Disease Duration Can Predict the Response to Allergen-specific Immunotherapy in Allergic Rhinitis.

Allergen-specific immunotherapy (AIT) has confirmed its efficacy in improving the symptoms of allergic rhinitis. However, no reliable biomarkers have been identified to predict the efficacy of AIT were found. We aimed to find clinical and immunological markers to predict efficacy in children after 2 years of sublingual immunotherapy (SLIT). A total of 285 children diagnosed with allergic rhinitis were recruited. The clinical efficacy was evaluated by comparing endpoint and baseline symptom and medication scores (SMS). Baseline clinical and immunological markers (serum total and specific immunoglobulin [Ig]E) and their correlation with clinical efficacy were analyzed. Of the 285 children recruited, 249 completed the 2-year SLIT program. After 2 years of SLIT, 68.3% of the children showed a significant response. Children in the Remarkable Response Group had the highest baseline SMS and most extended disease duration, followed by the Effective Relief and Unresponsive Group. Correlation analysis demonstrated that SMS improvement was positively correlated with baseline SMS (r=0.67) and disease duration (r=0.35). SMS improvement was not correlated with age, body mass index, total or specific IgE levels, or their ratios. Our results show that baseline SMS and disease duration can predict the efficacy of SLIT. Our study can guide the selection of suitable candidates for SLIT.

Inhibitory Effect of Apolipoprotein A-I on Eosinophils in Allergic Rhinitis in vitro and in vivo.

Purpose: Eosinophils have pivotal roles in the development of allergic rhinitis (AR) through the release of cytotoxic substances. Apolipoprotein A-I (Apo-AI) exhibits a strong inhibitory effect on eosinophil infiltration in allergic diseases. Nevertheless, the precise impact of Apolipoprotein A-I on eosinophils remains uncertain. Methods: Our study recruited a total of 15 AR children and 15 controls. The correlation between Apo-AI expression and the counts of blood eosinophils was examined. Flow cytometry was employed to assess the role of Apo-AI in eosinophil apoptosis and adhesion. The Transwell system was performed to conduct the migration assay. An animal model using AR mice was established to test the effect of Apo-AI on eosinophils. Results: Serum Apo-AI were negatively related to eosinophils counts and eosinophil chemotactic protein levels in AR. Apo-AI exerts a pro-apoptotic effect while also impeding the processes of adhesion, migration, and activation of eosinophils. The apoptosis triggered by Apo-AI was facilitated through the phosphoinositide 3-kinase (PI3K) pathway. The chemotaxis and activation of eosinophils, which are influenced by Apolipoprotein A-I, are regulated through the PI3K and MAPK signaling pathways. Apo-AI treated mice presented with decreased blood and nasal eosinophilic inflammation as well as down-regulated eosinophil related cytokines. Conclusion: Our findings provide confirmation that Apo-AI exhibits inhibitory effects on the function of eosinophils in allergic rhinitis. This suggests that Apo-AI holds potential as a therapeutic target for future treatment strategies.

Apolipoprotein A-I inhibited group II innate lymphoid cell response mediated by microRNA-155 in allergic rhinitis.

Background: Group 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting TH2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, has anti-inflammatory effects on neutrophils, monocytes, macrophages, and eosinophils. However, its effects on ILC2s are not well characterized. Objective: We aimed to investigate the effect of Apo-AI on the proliferation and function of ILC2s as well as its possible mechanism. Methods: The protein expression of Apo-AI and the percentage of ILC2s in peripheral blood between 20 allergic rhinitis patients and 20 controls were detected by ELISA and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function was detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI in vivo. Results: Elevated expression of Apo-AI was observed in allergic rhinitis patients. Apo-AI promotes ABCA1 expression by ILC2s, which can be inhibited by anti-Apo-AI. Apo-AI decreased ILC2 proliferation and the microRNA levels of GATA3 and RORα from ILC2s. The miR-155 overexpression promoted the upregulation of GATA3 and type II cytokines from ILC2s, while the addition of Apo-AI or miR-155 inhibitor significantly inhibited expression of GATA3 and type II cytokines by ILC2s. Apo-AI-/- mice showed as enhanced allergen-induced airway inflammation. The miR-155 inhibitor can reverse the enhanced allergen-induced airway inflammation in Apo-AI-/- mice, while miR-155 mimics can reverse the decreased allergen-induced airway inflammation in Apo-AI-treated mice. Conclusion: Apo-AI suppressed the proliferation and function of ILC2s through miR-155 in allergic rhinitis. Our data provide new insights into the mechanism of allergen-induced airway inflammation.

Genetically engineered nano-melittin vesicles for multimodal synergetic cancer therapy.

Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody-melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio-synthetically fabricated, with the recombinant protein (hGC33 scFv-melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14-responsive manner at tumor sites, which reduced off-target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small-molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co-delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.

Bacterium detected by gram stain and drug sensitivity in Chinese children with acute sinusitis.

BACKGROUND: Acute rhinosinusitis (ARS) is one of the common diseases of upper respiratory tract infection in children. Bacterial infection is a significant aggravating factor in pediatric ARS. In this research, our goal was to detected the bacterial flora and antibiotic sensitivity of ARS in Chinese children. METHODS: We recruited 133 children with ARS between January 2020 and January 2022 from our hospital. Sinus secretion were collected and cultured for Gram stain as well as antimicrobial susceptibility tests. RESULTS: Moraxella catarrhalis, Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa were detected in order in children with ARS, of which 25% were negative for bacterial culture and 10% were positive for two strains. Amoxicillin and clavulanate potassium were useful for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Quinolones are useful for Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. CONCLUSIONS: This research updates the proportion of ARS bacterial infection in children in southern China and the antibiotic sensitivity.

Efficacy and immunological changes of sublingual immunotherapy in pediatric allergic rhinitis.

Background: Allergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes. Methods: This retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months-1 year), the 2 years group (1-2 years), and the 3 years group (2-3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry. Results: The total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly. Conclusion: Our results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes.

Interleukin-37b Suppressed ILC2s in Children with Allergic Rhinitis.

Background: Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear. Methods: We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18Rα, and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA. Results: We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18Rα, and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years' SLIT, especially in the good response group. Conclusion: Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR.

Application of digital design combined with 3D-printing technologies in dental autotransplantation / 口腔疾病防治

Objective@#To evaluate the therapeutic effect of dental autotransplantation with the application of digital design combined with 3D printing of donor tooth models and recipient alveolar fossa model preoperatively.@*Methods@# Twelve cases that could not be retained due to tooth fracture or extensive absorption of alveolar bone were recruited in the study. Cone-beam computed tomography (CBCT) data were imported into Mimics software for digital design, and the best-matched third molar was selected as the donor tooth. Replicas of the donor teeth and the recipient socket were printed out with three-dimensional (3D) printing technologies as a simulation model for recipient tooth socket preparation. During tooth autotransplantation, preparation of the recipient tooth socket and the donor tooth were guided by the 3D-printed replicas sequentially. Then, the donor tooth was implanted into the recipient tooth pocket. Patients were followed up at 3, 6 and 12 months after the operation, with CBCT examination to evaluate the status of bone reconstruction and periodontal ligaments at each time point. @*Results@#Twelve patients were transplanted with an autogenous third molar with the apical foramen completely closed. Among them, 7 patients had alveolar fossa infection before the operation, of which 1 had extensive resorption of the alveolar bone due to the infection. All 12 patients recovered well after the operation and were followed up for at least 12 months. In total, 11 caseswere successful in tooth autotransplantation with normal mastication, and 1 case had root resorption 14 months postoperation.@*Conclusion@#Digital design combined with 3D printing technology can assistin the selection of thebest-matched donor tooth and preparation of the recipient socket before tooth transplantation proceduresand reduce the extra-alveolar exposure time of the donor tooth and number of trial placementsintothe alveolar fossa. Thus, this combined strategy can effectively improve the outcome of dental autotransplantation.

[Magnetic Resonance Imaging Features and Their Pathological Mechanisms of Hashimoto's Encephalopathy].

Objective To analyze the routine and functional magnetic resonance imaging(MRI) features and their potential pathological mechanisms of Hashimoto's encephalopathy(HE). Methods The clinical data and routine and functional MRI images of 30 HE patients who were treated in our center from January 2010 to April 2017 were retrospectively reviewed. Among them,15 patients were examined with contrast-enhanced MRI,16 with diffusion-weighed imaging(DWI),8 with magnetic resonance angiography,2 with magnetic resonance spectroscopy,and 1 with both arterial spin labeled perfusion imaging and diffusion tensor imaging. Seven patients had consecutive clinical and imaging data. The distribution,MRI signals,and functional MRI features of HE were analyzed. Results Among 30 HE patients,routine MRI showed negative results in 8 cases and abnormal findings in 22 cases. Among 22 abnormal cases,9 were characterized by small cerebral vascular disease and 13 had non-specific abnormalities;of these 13 cases,12 had lesions mainly located at the supratentorial white matter,11 had multiple lesions,and 2 had lesions complicated with cerebellum atrophy. The lesions were focal or confluent,punctate or small patchy,showing abnormal signal intensity with iso-or hypo-intensity on T1-weighed imaging,hyper-intensity on both T2-weighed imaging and fluid-attenuated inversion recovery. Most of the lesions had no enhancement(12/15). Among 7 cases with abnormalities on DWI,hyper-intensity on DWI and hypo-intensity on apparent diffusion coefficient were seen in 3 sudden acute cases and hyper-intensity on DWI and increased apparent diffusion coefficient value in 4 sub-acute or slow onset cases. Three cases showed localized intracranial artery stenosis. In 2 cases,magnetic resonance spectroscopy revealed significant lower N-acetylaspartate peak,higher choline peak,and visible lactate peak or lipid peak. Of 7 cases with follow-up data,3 cases had no change,4 cases had changes including softening lesions(2/4),remitted and relapsed lesions(1/4),and rapid progression of brain atrophy with negative finding on the initial MRI(1/4). Conclusion Routine MRI combined with functional imaging can show the features of HE from different perspectives. Routine MRI shows multifocal or confluent lesions in the white matter,mostly without enhancement,while functional imaging may reveal pathological characteristics of different phases of acute or chronic ischemia and demyelinating changes of HE. Combined with clinical data,MRI can differentiate HE from other diseases based on routine and functional MRI appearances.

[Determination of acrylamide residue in cosmetics by isotope dilution-liquid chromatography-tandem mass spectrometry].

Abstract: A comprehensive analytical method based on isotope dilution-liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of acrylamide residue in cosmetics. Water-soluble cosmetic sample was extracted with water, and the extract was centrifuged, then the upper solution was cleaned up by an Oasis HLB solid phase extraction cartridge. Oil-soluble cosmetic sample was extracted by liquid-liquid partition with n-hexane and water. The qualitative and quantitative analyses were carried out for the analyte in the multiple reaction monitoring (MRM) mode after the chromatographic separation on a Waters Atlantis T3 column (150 mm x 2.1 mm, 3 microm). The quantification was performed with 13C3-acrylamide as internal standard. The limit of quantification (LOQ) for acrylamide was 0.1 mg/kg. The mean recoveries were 87.7%-95.8% at the spiked levels of 0.1-1.0 mg/kg with the intra-day precision less than 10% and the inter-day precision less than 12%. The method is suitable for the determination of acrylamide in cosmetics.

Renal function and serum albumin at the start of dialysis in 514 Chinese ESRD in-patients.

BACKGROUND: The dialysis population has grown rapidly in recent decades. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are scant data about the level of renal function and the relationship of renal function and serum albumin at the start of dialysis in Chinese ESRD patients. METHOD: We report the level of serum creatinine (Scr), glomerular filtration rate (GFR), and serum albumin (Salb) in 514 ESRD in-patients who began their dialysis treatment between January 2001 through December 2007 at two large dialysis centers in Changsha, Hunan, China. Data were obtained through reviewing the case records of all 514 patients. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. In addition, serum albumin was analyzed in relation to levels of predicted GFR. RESULTS: The mean (SD) and median predialysis serum creatinine was 1121.92 +/- 458.24 and 1032 micromol/L. The mean (SD) and median predicted GFR was 4.98 +/- 2.24 and 4.47mL/min/1.73m(2). The proportion of patients with predicted GFR of >10, 5 to 10, and <5 mL/min/1.73m(2) was 3.7, 36.2, and 60.1%, respectively. The mean predicted GFR was significantly lower among younger patients, uninsured patients, unemployed or farmer patients, patients who were employed, students, patients who selected hemodialysis, patients with ESRD caused by diseases other than diabetes, patients with BUN above the mean, and patients with hemoglobulin beneath the mean. Compared with patients who started with GFR >5mL/min, the patients who started with GFR

Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium.

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.

Neurotoxicological consequence of long-term exposure to lanthanum.

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chronic renal failure (CRF), and the dosage is much higher than the daily intake of lanthanides. However, the effects of lanthanides on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether long-term lanthanum exposure results in persistent alternations in nervous system function. Wistar rats were exposed to lanthanum chloride (LaCl(3)) through oral administration at 0, 0.1, 2 and 40mg/kg concentration from 4 weeks through 6 months of age. Morris water maze test showed that lanthanum exposure at 40mg/kg could significantly impair the behavioral performance. To fully investigate the neurotoxicological consequence of lanthanum exposure, brain elemental distributions and neurochemicals were also investigated. The distributions of brain elements such as Ca, Fe and Zn were significantly altered after lanthanum exposure. Moreover, 40mg/kg LaCl(3) significantly inhibited the activity of Ca(2+)-ATPase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters were significantly decreased. These findings indicate that chronic exposure to lanthanum could possibly impair the learning ability and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in brain. Therefore, the application of lanthanide, especially in pharmacology, should be cautious.

Long-term effects of lanthanum intake on the neurobehavioral development of the rat.

The effects of subchronic exposure to lanthanum on rats' physical and neurobehavioral development were investigated. Wistar rats were exposed to lanthanum through oral administration at 0, 0.1, 2, and 40 mg/kg concentrations from gestation day 0 through 5 months of age. Prior to weaning of the pups, physical parameters and neurobehaviors were assessed, including body weight gain, pinna detachment, eye opening, surface righting reflex and swimming endurance. At 30 days of age, DNA concentration and protein/DNA ratio of the whole brain were determined. At 150 days of age, the Morris water maze test was carried out to study the memory and learning abilities of the rats. Differences were found in the body weight gain, surface righting reflex and swimming endurance. Moreover, lanthanum exposure significantly altered the DNA concentration and Protein/DNA in brain. The Morris water maze test showed that lanthanum exposure at 40 mg/kg significantly impaired memory and learning abilities. These findings indicate that lanthanum is a potential behavior teratogen. The information provided by this work should be considered in future applications of lanthanides.

Accumulation and distribution of samarium-153 in rat brain after intraperitoneal injection.

It is well known that rare earth elements (REEs) have come into extensive use in a number of fields. As a result, REEs are becoming closely related to human's daily life. However, until now, the distributions of REEs in the brain are not yet very clear. In this study, Sprague-Dawley male rats were intraperitoneally injected with 0.25 mL of (153)SmCl(3) solution (containing 10 microg Sm). The brains were perfused with saline to minimize the blood influence. The radioactivities of (153)Sm in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum, and cerebral cortex) were counted. The results suggested that Sm did enter into the brain. Although only about 0.0003% of the given dose was accumulated in the brain, Sm seemed to be remain in the brain for a long time. The highest amounts and lowest concentrations of (153)Sm were found in the cerebral cortex, and the highest concentrations of (153)Sm were found in the hypothalamus.

Distribution of ytterbium-169 in rat brain after intravenous injection.

It is well known that lanthanides have come into extensive and rapid use in a number of fields. As a result, more and more lanthanides are getting into the environment and food chains. However, the distributions of lanthanides in brain are not yet very clear. In this study, adult Sprague-Dawley male rats were intravenously injected with 0.5 ml of 169YbCl3 solution (containing 10 microg Yb). The brains were perfused with saline to minimize the blood influence. The radioactivities of 169Yb in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum and cerebral cortex) were counted. The results suggested that Yb did enter into the brain. Though only about 0.005% of the given dose was accumulated in the brain, Yb seemed to remain in the brain for long time. The highest specific activities were observed in the hypothalamus, hippocampus and cerebellum.