Supramolecular prodrug of SN38 based on endogenous albumin and SN38 prodrug modified with semaglutide side chain to improve the tumor distribution.

To improve the biodistribution of the drug in the tumor, a supramolecular prodrug of SN38 was fabricated in situ between endogenous albumin and SN38 prodrug modified with semaglutide side chain. Firstly, SN38 was conjugated with semaglutide side chain and octadecanedioic acid via glycine linkers to obtain SI-Gly-SN38 and OA-Gly-SN38 prodrugs, respectively. Both SI-Gly-SN38 and OA-Gly-SN38 exhibited excellent stability in PBS for over 24 h. Due to the strong binding affinity of the semaglutide side chain with albumin, the plasma half-life of SI-Gly-SN38 was 2.7 times higher than that of OA-Gly-SN38. Furthermore, with addition of HSA, the fluorescence intensity of SI-Gly-SN38 was 4 times higher than that of OA-Gly-SN38, confirming its strong binding capability with HSA. MTT assay showed that the cytotoxicity of SI-Gly-SN38 and OA-Gly-SN38 was higher than that of Irinotecan. Even incubated with HSA, the SI-Gly-SN38 and OA-Gly-SN38 still maintained high cytotoxicity, indicating minimal influence of HSA on their cytotoxicity. In vivo pharmacokinetic studies demonstrated that the circulation half-life of SI-Gly-SN38 was twice that of OA-Gly-SN38. SI-Gly-SN38 exhibited significantly reduced accumulation in the lungs, being only 0.23 times that of OA-Gly-SN38. The release of free SN38 in the lungs from SI-Gly-SN38 was only 0.4 times that from OA-Gly-SN38 and Irinotecan. The SI-Gly-SN38 showed the highest accumulation in tumors. The tumor inhibition rate of SI-Gly-SN38 was 6.42% higher than that of OA-Gly-SN38, and 8.67% higher than that of Irinotecan, respectively. These results indicate that the supramolecular prodrug delivery system can be constructed between SI-Gly-SN38 and endogenous albumin, which improves drug biodistribution in vivo, enhances tumor accumulation, and plays a crucial role in tumor growth inhibition.

Enhancing SN38 prodrug delivery using a self-immolative linker and endogenous albumin transport.

Enhancing the delivery and release efficiency of hydroxyl agents, constrained by high pKa values and issues of release rate or unstable linkage, is a critical challenge. To address this, a self-immolative linker, composed of a modifiable p-hydroxybenzyl ether and a fast cyclization adapter (N-(ortho-hydroxyphenyl)-N-methylcarbamate) was strategically designed, for the synthesis of prodrugs. The innovative linker not only provides a side chain modification but also facilitates the rapid release of the active payloads, thereby enabling precise drug delivery. Particularly, five prodrug model compounds (J1, J2, J3, J5 and J6) were synthesized to evaluate the release rates by using ß-glucuronic acid as trigger and five hydroxyl compounds as model payloads. Significantly, all prodrug model compounds could efficiently release the hydroxyl payloads under the action of ß-glucuronidase, validating the robustness of the linker. And then, to assess the drug delivery and release efficiency using endogenous albumin as a transport vehicle, J1148, a SN38 prodrug modified with maleimide side chain was synthesized. Results demonstrated that J1148 covalently bound to plasma albumin through in situ Michael addition, effectively targeting the tumor microenvironment. Activated by ß-glucuronidase, J1148 underwent a classical 1, 6-elimination, followed by rapid cyclization of the adapter, thereby releasing SN38. Impressively, J1148 showed excellent therapeutic efficacy against human colonic cancer xenograft model, leading to a significant reduction or even disappearance of tumors (3/6 of mice cured). These findings underscore the potential of the designed linker in the delivery system of hydroxyl agents, positioning it at the forefront of advancements in drug delivery technology.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Transcriptome Sequencing Analysis of circRNA in Skeletal Muscle between Fast- and Slow-Growing Chickens at Embryonic Stages.

Skeletal muscle growth has always been the focus of the broiler industry, and circRNAs play a significant role in this process. We collected leg muscles of slow- and fast-growing Bian chicken embryos in the study at 14 (S14 and F14) and 20 (S20 and F20) days for RNA-seq. Finally, 123 and 121 differentially expressed circRNAs (DECs) were identified in S14 vs. F14 and S20 vs. F20, respectively. GO enrichment analysis for DECs obtained important biological process (BP) terms including nicotinate nucleotide biosynthetic process, nicotinate nucleotide salvage, and NAD salvage in S20 vs. F20 and protein mannosylation in S14 vs. F14. KEGG pathway analysis showed Wnt signaling pathway, Tight junction, Ubiquitin mediated proteolysis, and Notch signaling pathway were enriched in the top 20. Based on the GO and KEGG analysis results, we found some significant host genes and circRNAs such as NAPRT and novel_circ_0004547, DVL1 and novel_circ_0003578, JAK2 and novel_circ_0010289, DERA and novel_circ_0003082, etc. Further analysis found 19 co-differentially expressed circRNAs between the two comparison groups. We next constructed a circRNA-miRNA network for them, and some candidate circRNA-miRNA pairs related to skeletal muscle were obtained, such as novel_circ_0002153-miR-12219-5p, novel_circ_0003578-miR-3064-3p, and novel_circ_0010661-miR-12260-3p. These results would help to reveal the mechanism for circRNAs in skeletal muscle and also provide some guidance for the breeding of broilers.

Analysis of genome and methylation changes in Chinese indigenous chickens over time provides insight into species conservation.

Conservation of natural resources is a vital and challenging task. Numerous animal genetic resources have been effectively conserved worldwide. However, the effectiveness of conservation programmes and the variation information of species have rarely been evaluated. Here, we performed whole-genome and whole-genome bisulfite sequencing of 90 Chinese indigenous chickens, which belonged to the Tibetan, Wenchang and Bian chicken breeds, and have been conserved under different conservation programmes. We observed that low genetic diversity and high DNA methylation variation occurs during ex situ in vivo conservation, while higher genetic diversity and differentiation occurs during in situ conservation. Further analyses revealed that most DNA methylation signatures are unique within ex situ in vivo conservation. Moreover, a high proportion of differentially methylated regions is found in genomic selection regions, suggesting a link between the effects of genomic variation and DNA methylation. Altogether our findings provide valuable information about genetic and DNA methylation variations during different conservation programmes, and hold practical relevance for species conservation.

Transcriptome Integration Analysis at Different Embryonic Ages Reveals Key lncRNAs and mRNAs for Chicken Skeletal Muscle.

The growth and development of skeletal muscle at embryonic stages are vital and it directly affects the growth performance of chickens. Long non-coding RNA (lncRNA) plays an important role in this process. In the experiment, we collected the leg muscles of fast- and slow-growing Bian chickens both at 14- and 20-day embryo ages (14E and 20E) for RNA-seq. Finally, 292 and 347 differentially expressed (DE) lncRNAs were identified in F14vsF20 and S14vsS20, and 1,295 and 1,560 DE mRNAs were also screened, respectively. Then we constructed lncRNA-mRNA networks for the two groups, respectively, and found that 6 of the top 10 lncRNAs ranked with degree are same. GO analysis showed that 12 of the top 20 terms were same in the two comparison groups and most of them were related to energy metabolisms, such as cellular respiration and aerobic respiration. KEGG enrichment revealed that up to 16 pathways of the top 20 in F14vsF20 were same as that of S14vsS20 and most of them were related to growth, including citrate cycle (TCA cycle) and oxidative phosphorylation. Further analysis showed that there were 602 and 102 same DE mRNAs and DE lncRNAs between the two comparison groups. We then identified 442 lncRNA-mRNA pairs, including 201 mRNAs and 32 lncRNAs. Protein-Protein Interactions (PPI) network was predicted for the 201 mRNAs and three core networks were obtained using the plug-in MCODE of Cytoscape. Then the function of genes in the three core networks was further analyzed with ClueGo and they were mainly enriched in six groups of biological processes. On this basis, combined with KEGG pathways and lncRNA-mRNA networks, we identified several candidate lncRNAs and mRNAs. Among them, lncRNAs mainly include TCONS_00061389, TCONS_00025495, TCONS_00017622, TCONS_00216258 and TCONS_00084223, and mRNAs include PLK1, BUB1, TTK, NDUFS7 NDUFAB1, PDHA1, CDK1, SDHA, ACO2 and MDH1. The results would provide a foundation for further experiments on the role of lncRNAs in the regulation of muscle development. And it could also contribute to further clarify the regulatory mechanism of chicken skeletal muscle.

Identification of crucial circRNAs in skeletal muscle during chicken embryonic development.

BACKGROUND: Chicken provides humans with a large amount of animal protein every year, in which skeletal muscle plays a leading role. The embryonic skeletal muscle development determines the number of muscle fibers and will affect the muscle production of chickens. CircRNAs are involved in a variety of important biological processes, including muscle development. However, studies on circRNAs in the chicken embryo muscle development are still lacking. RESULTS: In the study, we collected chicken leg muscles at 14 and 20-day embryo ages both in the fast- and slow-growing groups for RNA-seq. We identified 245 and 440 differentially expressed (DE) circRNAs in the comparison group F14vsF20 and S14vsS20 respectively. GO enrichment analysis for the host genes of DE circRNAs showed that biological process (BP) terms in the top 20 related to growth in F14vsF20 were found such as positive regulation of transcription involved in G1/S phase of mitotic cell cycle, multicellular organismal macromolecule metabolic process, and multicellular organismal metabolic process. In group S14vsS20, we also found some BP terms associated with growth in the top 20 including actomyosin structure organization, actin cytoskeleton organization and myofibril assembly. A total of 7 significantly enriched pathways were obtained, containing Adherens junction and Tight junction. Further analysis of those pathways found three crucial host genes MYH9, YBX3, IGF1R in both fast- and slow-growing groups, three important host genes CTNNA3, AFDN and CREBBP only in the fast-growing group, and six host genes FGFR2, ACTN2, COL1A2, CDC42, DOCK1 and MYL3 only in the slow-growing group. In addition, circRNA-miRNA network also revealed some key regulation pairs such as novel_circ_0007646-miR-1625-5p, novel_circ_0007646-miR-1680-5p, novel_circ_0008913-miR-148b-5p, novel_circ_0008906-miR-148b-5p and novel_circ_0001640-miR-1759-3p. CONCLUSIONS: Comprehensive analysis of circRNAs and their targets would contribute to a better understanding of the molecular mechanisms in poultry skeletal muscle and it also plays an important guiding role in the next research.

Comparative Analysis of miRNA Expression Profiles in Skeletal Muscle of Bian Chickens at Different Embryonic Ages.

MicroRNAs (miRNAs) are widely involved in the growth and development of skeletal muscle through the negative regulation of target genes. In order to screen out the differentially expressed miRNAs (DEMs) associated with skeletal muscle development of Bian chickens at different embryonic ages, we used the leg muscles of fast-growing and slow-growing Bian chickens at the 14th and 20th embryonic ages (F14, F20, S14 and S20) for RNA-seq. A total of 836 known miRNAs were identified, and 121 novel miRNAs were predicted. In the F14 vs. F20 comparison group, 127 DEMs were screened, targeting a total of 2871 genes, with 61 miRNAs significantly upregulated and 66 miRNAs significantly downregulated. In the S14 vs. S20 comparison group, 131 DEMs were screened, targeting a total of 3236 genes, with 60 miRNAs significantly upregulated and 71 miRNAs significantly downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the predicted target genes were significantly enriched in 706 GO terms and 6 KEGG pathways in the F14 vs. F20 group and 677 GO terms and 5 KEGG pathways in the S14 vs. S20 group. According to the interaction network analysis, we screened five coexpressed DEMs (gga-miR-146a-3p, gga-miR-2954, gga-miR-34a-5p, gga-miR-1625-5p and gga-miR-18b-3p) with the highest connectivity degree with predicted target genes between the two comparison groups, and five hub genes (HSPA5, PKM2, Notch1, Notch2 and RBPJ) related to muscle development were obtained as well. Subsequently, we further identified nine DEMs (gga-let-7g-3p, gga-miR-490-3p, gga-miR-6660-3p, gga-miR-12223-5p, novel-miR-327, gga-miR-18a-5p, gga-miR-18b-5p, gga-miR-34a-5p and gga-miR-1677-3p) with a targeting relationship to the hub genes, suggesting that they may play important roles in the muscle development of Bian chickens. This study reveals the miRNA differences in skeletal muscle development between 14- and 20-day embryos of Bian chickens from fast- and slow-growing groups and provides a miRNA database for further studies on the molecular mechanisms of the skeletal muscle development in Bian chickens.

Prevalence and risk factors of allergic rhinitis and asthma in the southern edge of the plateau grassland region of northern China: A cross-sectional study.

BACKGROUND: The prevalence rates of allergic rhinitis (AR) and asthma in the border region of China may be different from those in the central region of plateau grasslands. A survey was performed to investigate the prevalence and risk factors for AR, asthma, and AR combined with asthma among adults (age ≥ 20 years) residing in the southern border of plateau grasslands in northern China. METHODS: From May to August 2018, a cross-sectional survey was completed by subjects that were selected using a cluster random sampling method. The subjects completed a questionnaire and were administered skin prick tests (SPTs). Risk factors for AR, asthma, and AR combined with asthma were examined by multivariate logistic regression analyses. RESULTS: A total of 1815 adult subjects in the selected region completed study. The prevalence rates of physician-diagnosed AR, asthma, and AR combined with asthma were 13.9% (253), 9.8% (177), and 2.9% (52), respectively. Among the patients with AR, 20.6% were found to have concurrent asthma; among the patients with asthma, 29.4% were found to have concurrent AR. Artemisia and Humulus pollen were the most common sensitizing pollen types. Approximately 70% of subjects with AR and <30% of asthma patients were sensitized to Artemisia and Humulus pollen. Symptoms of AR and asthma mainly appeared during August. A multivariable logistic regression analysis identified sensitization pollen as an independent risk factor for both AR and AR combined with asthma (AR: OR = 16.23, 95% CI: 10.15-25.96; AR combined with asthma: OR = 6.16, 95% CI: 1.28-29.66). An age >40 years old, family history of asthma, moderate-to-severe AR, adverse food reactions, and mold allergies were independent risk factors for AR combined with asthma. CONCLUSIONS: This study identified the prevalence rates of AR and asthma in the southern borders of the plateau grassland in northern China (>1500 m above sea level). Sensitization pollen is an independent risk factor for AR and AR combined with asthma.

Safety of semi-depot house dust mite allergen extract in children and adolescents with allergic rhinitis and asthma.

Aim: Multicenter study to investigate the safety of mite extract product Novo-Helisen Depot, Strengths 1 to 3 (NHD3), as subcutaneous immunotherapy (SCIT), in Chinese children and adolescents with allergic rhinitis (AR) and allergic asthma (AA). Patients & methods: We evaluated SCIT-related adverse events (AEs) during NHD3 14-week initial therapy in children (5-11 years) and adolescents (12-17 years) with perennial symptomatic AR and AA. Results: Among 3600 injections in 250 patients, 361/3600 (10.0%) injections caused SCIT-related AEs in 96/250 (38.4%) patients, 321/3600 injections (8.9%) caused local reactions in 89/250 (35.6%) and 40/3600 injections (1.1%) caused systemic reactions in 23/250 (9.2%). Conclusion: Initial SCIT treatment using NHD3 was safe and well tolerated in Chinese children and adolescents with AR and AA.

Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.

Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs. Methods: Artemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders. Results: Artemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT. Conclusion: Serum LTA4H may be a potential biomarker for early prediction of an effective AIT.

[Analysis of sensitization characteristics of artemisia pollen in the Inner Mongolian grassland region of China].

Objective:The distribution and sensitization characteristics of the pollen of artemisia were analyzed in the grasslands of Inner Mongolian. Method:A face-to-face questionnaires survey about the distribution and sensitization characteristics of the pollen of artemisia was performed together with pollen skin prick tests（SPTs） and measurements of the daily pollen count in 6 region（Xilinhot, Erenhot, Duolun, Tongliao, Jarud, Kailu） in the grasslands of Inner Mongolian. Result:A total of 6043 subjects completed the study. The prevalence of artemisia hay fever was 14.38%（869/6043）. The highest prevalence was found in the 18-39 age group（43.27%, 376/869）. Subjects from urban areas showed higher prevalence of AR than from rural areas（61.22% vs. 38.78%, P<0.01）. There were significant regional differences in the prevalence of AR（P<0.01） among the six areas investigated. The main clinical symptoms of artemisia hay fever were sneezing（96.78%） and itchy nose（91.60%）. The main clinical symptoms of ocular were itchy（68.58%）. Among associated symptoms of artemisia hay fever, fatigue and somnolence were common. The peak season of artemisia hay fever was in August. The season of onset of artemisia hay fever coincides with the peak time of pollen dispersal of artemisia. The SPT positive of artemisia pollen in the investigated 6043 people was 23.98%. Among comorbidities, allergic conjunctivitis accounts for 70.77% （615）, food allergy accounts for 85.85% （746）, asthma accounts for 9.55% （83）. Conclusion:The prevalence of artemisia hay fever in grassland of northern china stays at a high level. It is very important to control artemisia hay fever.

Artemisia Annua sublingual immunotherapy for seasonal allergic rhinitis: A multicenter, randomized trial.

BACKGROUND: Artemisia annua is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for Artemisia annua-induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for Artemisia annua-related AR. METHODS: This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 Artemisia annua-sensitized eligible patients were randomized in a ratio of 2:1 to receive Artemisia annua-SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced. RESULTS: Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 ± 0.47 vs 1.88 ± 0.42, P < 0.0001 in full analysis set [FAS]; 1.49 ± 0.52 vs 1.95 ± 0.46, P < 0.0001 in per protocol set [PPS]); representing a 22.3% and 23.6% reduction, respectively, relative to placebo. In specifically Artemisia annua monosensitized patients, mean daily CSMRS reductions were demonstrated as 24.1% and 27.0% in the FAS and PPS populations, respectively, when comparing the active treatment to placebo treatment. Similarly, SLIT decreased dTNSS in peak pollen period by 19.0% in FAS and 22.3% in PPS, respectively, relative to placebo. In coincidence, dRMS in peak pollen period was reduced by 22.0% in FAS and 26.0% in PPS. 65.8% patients in SLIT group experienced treatment-related AEs, none of which was serious. CONCLUSION: This study indicates that SLIT with Artemisia annua drops is an effective and safe treatment option in Chinese patients with Artemisia Annua-induced AR.

[Distribution characteristics of Chinese medicine resources in Turpan Basin, Xinjiang].

Based on the results of the fourth national survey of traditional Chinese medicine resources in Turpan city, Xinjiang, this study counted the types of traditional Chinese medicine resources in Turpan Basin. The spatial distribution differences of traditional Chinese medicine resources in Turpan Basin of Xinjiang were analyzed by using grid technology, trend surface analysis, global spatial autocorrelation analysis, and local spatial autocorrelation analysis, so as to clarify the overall change trend and aggregation degree of traditional Chinese medicine resources in Turpan Basin in horizontal and vertical directions. The results showed the following: in the horizontal direction, the species richness of traditional Chinese medicine resources in the central part of Turpan Basin was high, and there were great differences in the species richness of traditional Chinese medicine resources in Turpan Basin under different grid sizes. The spatial scale effect of the richness of traditional Chinese medicine resources in Turpan Basin is obvious. Among them, under the 30 km×30 km scale, the richness of the types of Chinese medicine resources shows a high spatial correlation, and the richness of the types of Chinese medicine resources at 5 km×5 km scale presents a near random distribution state, and the richness of the types of Chinese medicine resources at 80, 90, and 100 km scale sits negatively related. Vertical direction, Chinese medicine resources appear rich at the range of-154-150 m and 900-1 050 m following by range of 1 050-1 200 m.

MicroRNA-625 inhibits cell invasion and epithelial-mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma.

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC. MATERIALS AND METHODS: LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3'-UTR of SOX4. RESULTS: The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells. CONCLUSIONS: Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease.

Chinese Guideline on allergen immunotherapy for allergic rhinitis.

The present document is based on a consensus reached by a panel of experts from Chinese Society of Allergy (CSA) and Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G). Allergen immunotherapy (AIT), has increasingly been used as a treatment for allergic rhinitis (AR) globally, as it has been shown to provide a long-term effect in improving nasal and ocular symptoms, reducing medication need, and improving quality of life. AIT is currently the only curative intervention that can potentially modify the immune system in individuals suffering from AR and prevent the development of new sensitization and the progression of disease from AR to asthma. Although the use of AIT is becoming more acceptable in China, to date no AR immunotherapy guideline from China is available for use by the international community. This document has thus been produced and covers the main aspects of AIT undertaken in China; including selection of patients for AIT, the allergen extracts available on the Chinese market, schedules and doses of allergen employed in different routes of AIT, assessment of effect and safety, patients' administration and follow-up, and management of adverse reactions. The Chinese guideline for AR immunotherapy will thus serve as a reference point by doctors, healthcare professionals and organizations involved in the AIT of AR in China. Moreover, this guideline will serve as a source of information for the international community on AIT treatment strategies employed in China.

The impact of lncRNA MG3 on laryngeal cancer cell growth, cycle, and apoptosis related factors.

Laryngeal cancer is a common head and neck malignant tumor. Long non-coding RNA (lncRNA) is a kind of RNA at the length more than 200 nucleotides that cannot code protein. They widely exist in the human genome. Maternally expressed gene 3 (MG3) is a kind of lncRNA that is associated with various malignant tumors development. This study explores the influence of MG3 on laryngeal cancer Hep-2 cell growth, cycle, and apoptosis related factors. Hep2 cells transfected by MG3 were treated as experimental group, while untransfected Hep2 cells were treated as control. MG3 expression was tested by real time PCR. Cell proliferation was evaluated by MTT assay. Cell cycle was determined by flow cytometry. Bcl-2, Bax, and survivin protein levels were detected by Western blot. MG3 expression significantly increased in Hep2 cells compared with control (P < 0.05). Hep2 cell OD value and cell percentage in S phase were obviously declined, while cell apoptosis were markedly enhanced (P < 0.05). OD value and cell percentage in S phase apparently reduced in 12 h, 24 h, and 48 h from experimental group (P < 0.05). Bcl-2 and survivin protein downregulated, while Bax protein elevated in experimental group following time extension (P < 0.05). MG3 overexpression inhibited laryngeal cancer Hep2 cell proliferation and arrested cell cycle with time dependence, which may achieve by suppressing Bcl-2 and survivin protein, and facilitating Bax protein expression.

[Expression and significance of phosphated signal transducer and activator of transcription 3 and p53 protein in laryngeal squamous cell carcinoma].

OBJECTIVE: To investigate the expression and clinical significance of phosphated signal transducer and activator of transcription 3 (p-STAT3) and p53 protein in laryngeal squamous cell carcinoma (LSCC), and the relationship between the two genes. METHOD: Formalin-fixed and paraffin-embedded tissues, which came from 60 cases of LSCC and 32 samples of normal mucosa over 2.0 cm away from tumor margin in 32 patients with total or subtotal laryngectomy were detected for the expression of p-STAT3 and p53 protein by in SP immunohistochemistry. Micro-image analysis system was used to determine the optical density,and the result was analyzed statistically. RESULT: There is over expression of p-STAT3 and p53 protein in LSCC. The expression of p-STAT3 and p53 protein in LSCC was associated with clinical stage and lymph nodal metastases (P < 0.05). There was a positive correlation between the expression of p-STAT3 and P53 protein. The correlation coefficient (r) was 0.6558 (P < 0.01). CONCLUSION: The expression of p-STAT3 and p53 protein may play an important role in the tumorigenesis,metastases and poor prognosis of LSCC. There was a positive correlation between the over expression of p-STAT3 and p53 protein in LSCC.

[Automobile tyre colloidal particle induced allergic damage of respiratory system in traffic policemen and its allergenicity].

OBJECTIVE: To explore the damage of respiratory system in the traffic policemen induced by automobile tyre colloidal particle and its allergenicity. METHODS: The respiratory system symptoms in 445 traffic policemen working outside their offices and 243 controls were investigated and their pulmonary ventilation function index such as FVC, FEV(1.0), MMF and V(50) were determined. The specific IgE antibody of automobile tyre colloidal particle of their serum was determined and the skin-prick test of automobile tyre colloidal particle antigen was performed. Sixty-six traffic policemen working outside their offices and 5 controls with the positive of IgE antibody among them were detected by nasal mucosa provocation test. Sixty-six traffic policemen working outside their offices with the positive of IgE antibody were determined by Terbutaline inhalation test. RESULTS: The positive rate of respiratory system symptoms of traffic policemen such as cough, stethocatharsis, short breath, nasal obstruction, sneeze and nose running was 38.02%, 27.03%, 20.00%, 23.08%, 27.47%, 32.09% and 34.95% respectively and significantly higher than those of the control with significant difference (P < 0.01) or (P < 0.05). The positive rate of specific IgE antibody of automobile tyre colloidal particle, skin- prick test and nasal mucosa provocation test was 14.51%, 23.73% and 54.55% respectively with significant difference (P < 0.01) and (P < 0.05). The percentage, the actual figure compared with the prediction figure, of the index of pulmonary ventilation function (FVC, FEV(1.0) MMF and V(50)) of traffic policemen were significantly lower than those of the control. Terbutaline inhalation test in 66 positive subjects of specific IgE antibody of automobile tyre colloidal particle was positive in 44 subjects, accounting for 9.67% in all policemen investigated. CONCLUSION: The automobile tyre colloidal particle is one of etiological factors that induce pulmonary ventilation function damage and could result in allergic asthma of traffic police.