BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective:To observe and analyze the levels of vitamin D（VD） and their influencing factors in children undergoing adenoidectomy and/or tonsillectomy. Methods:A total of 147 children who received adenoidectomy and/or tonsillectomy in our hospital from November 2018 to March 2019 were selected as the experimental groups, gender and age matched 147 healthy children of the same period were selected as the control group. The differences of VD levels between the two groups were compared, the factors affecting VD levels were investigated, and patients with VD deficiency/insufficiency in the experimental groups were followed up postoperatively. Results:The VD levels of the experimental groups were（19.6±6.6） ng/mL and those of the control groups were （22.5±6.5）ng/mL, which was significantly different （P<0.01）. The experimental groups were divided into inflammation groups and Sleeping disorder breathing（SDB）groups. The VD levels of the two groups were （19.1±6.7）ng/mL and （21.9±6.4）ng/mL, which was significantly different （P<0.05）. Regression analysis showed that VD levels were negatively correlated with age, body mass index （BMI）, adenoid hypertrophy, tonsil hypertrophy and Anti-streptolysin O（ASO）levels （P<0.05）. VD values were remeasured one year postoperatively in 23 of 72 children in the VD deficiency/deficiency groups, and there was a statistically significant difference between preoperative and postoperative VD values[（14.3±3.9）ng/mL and （17.1±5.5） ng/mL, respectively, P<0.05]. There was a significant difference in postoperative VD value between the inflammation groups and the SDB groups[ （15.6±5.9） ng/mL and （20.5±2.1） ng/mL, respectively, P<0.05]. Conclusion:Children who underwent adenoidectomy and/or tonsillectomy had lower VD levels than healthy children.VD levels decreased with increasing age,BMI and ASO values,and associated with the size of adenoid and tonsil. Preoperative VD levels were lower in the inflammation groups, adenoidectomy and/or tonsillectomy improved VD deficiency/insufficiency status, and postoperative elevation of VD levels was more pronounced in the SDB groups.
Humans ; Tonsillectomy ; Adenoidectomy ; Vitamin D/blood* ; Vitamin D Deficiency ; Male ; Female ; Postoperative Period ; Child ; Case-Control Studies ; Child, Preschool

Objectives:To explore the clinical characteristics of children with adenoid hypertrophy (AH) and laryngopharyngeal reflux (LPR) by detecting the expression of pepsin in adenoids as a standard for AH with LPR.Methods:A total of 190 children who were admitted for surgical treatment due to AH were included in the study. The main clinical symptoms of the patients were recorded, and the degree of adenoid hypertrophy was evaluated. Before the surgery, Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were used to evaluate the reflux symptoms. After the surgery, pepsin immunohistochemical staining was performed on the adenoid tissue, and according to the staining results, the patients were divided into study group (pepsin staining positive) and control group (pepsin staining negative). SPSS 19.0 software was used for statistical analysis. Quantitative data conforming to normal distribution between the two groups were tested by two-independent sample t test, and quantitative data with skewed distribution were tested by Mann-Whitney U test. Results:The positive rate of pepsin staining in the 190 AH patients was 78.4% (149/190). The study group had higher levels of preoperative symptoms such as erythema and/or congestion of the pharynx(2.1±0.7 vs. 1.8±0.6, t=2.23), vocal cord edema[1.0(0, 1.0) vs. 1.0(0, 1.0), Z=2.00], diffuse laryngeal edema[0(0, 1.0) vs. 0(0, 0), Z=2.48], posterior commissure hypertrophy[(1.4±0.6 vs. 1.1±0.5), t=2.63], and a higher total score on the RFS scale than the control group(6.2±2.7 vs. 5.0±2.6, t=2.47), with statistical differences ( P<0.05). The sensitivity and specificity of RFS score in diagnosing AH with LPR were 24.8% and 80.5%, respectively. When RFS>5 was used as the positive threshold, the sensitivity and specificity of RFS score in diagnosing AH with LPR were 61.1% and 58.5%, respectively. There was a statistical difference in the number of positive cases of RFS score between the study group and the control group(91 vs. 17, χ2=5.04, P=0.032). Conclusions:LPR is common in AH children. Children with AH and LPR have specific performance in electronic laryngoscopy, such as erythema with edema in the pharynx, posterior commissure hypertrophy, and vocal cord edema.

Objective:Pediatric chronic sinusitis （CRS） is a common disease within the field of otolaryngology-head and neck surgery. Due to the immaturity of sinus development and immune competence in children, its etiology and pathophysiology are complex, and its clinical features and outcomes differ significantly from those in adult patients. Currently, there are issues in the diagnosis and treatment of pediatric CRS, particularly in areas such as antibiotic use and surgical interventions, owing to a lack of sufficient attention. In recognition of this, the Chinese Rhinopathy Research Cooperation Group developed this expert consensus based on a systematic review of the latest literatures from both domestic and international sources, with reference to the latest evidence-based medical evidence worldwide, and in combination with their own clinical experience. The consensus covers various aspects including epidemiology, predisposing factors, pathophysiology, diagnosis and differential diagnosis, as well as treatment strategies such as medical therapy and surgical intervention. It aims to standardize the clinical diagnosis and treatment of pediatric CRS, improve clinical efficacy and patient satisfaction, reduce clinical expenditures, and decrease the occurrence of adverse reactions.
Humans ; Sinusitis/therapy* ; Chronic Disease ; Child ; Consensus ; Anti-Bacterial Agents/therapeutic use*

Fibroblast activating protein (FAP) is an important biomarker of cancer associated fibroblasts and activated fibroblasts, which is highly expressed in activated fibroblasts of many tumor and fibrotic tissues, but not in normal tissues and non malignant lesions. Therefore, FAP has become an excellent target for diagnosis and treatment of tumors and other diseases. PET imaging and internal radiotherapy based on FAP inhibitor (FAPI) have been used in the diagnosis and treatment of many diseases, such as cancer and fibrosis. We first introduce the mechanism of disease occurrence and progression mediated by FAP and its clinical significance as a therapeutic target.Then,we systematically summarize the FAP probes labeled with 125I, 68Ga, 64Cu and other radionuclides, including their structural evolution, imaging, biodistribution and pharmacokinetic properties.After that, the reported strategies to improve the pharmacokinetic properties and target affinity of probes are summarized, including the use of squaramide linkers,modification with albumin binding agent,the development of dual-targeting probes.Finally, some suggestions for the future development of novel radioactive probes targeting FAP and the clinical application of classical probes are proposed.

Objective:To analyze the prevalence of allergic rhinitis in Chinese children from 2001 to 2021, in order to provide data support for the prevention and treatment of allergic rhinitis in children.Methods:"Allergic rhinitis" "children" "adolescent" "infant" "prevalence" "epidemiology" were used in the main search terms. The combination of Mesh words and free words was adopted. CNKI, CBM, VIP, WanFang Data, PubMed, Web of Science, Embase and The Cochrane Library for publications between January 1, 2001 and December 31, 2021 were searched systemically and data were extracted from eligible studies by two independent reviewers. Supplementary collection was made by identifying retrospective references from the included literature. After study quality assessment, Meta analysis was completed using Stata 16.0 software.Results:A total of 20 cross-sectional studies were included, involving 54 886 cases. Meta analysis results showed that the overall prevalence of allergic rhinitis among the participants was 18.46% (95% CI:14.34%-22.59%). Subgroup analysis showed that the prevalence of allergic rhinitis from 2012 to 2021 (19.75%) was higher than that from 2001 to 2011 (14.81%), and the difference was statistically significant ( P<0.001). The prevalence of different regions from high to low was East China (22.77%), North China (20.82%), Northwest China (17.77%), Central China (16.62%), Southwest China (16.33%), Northeast China (16.16%) and South China (7.29%) respectively, the difference was statistically significant ( P<0.001). The prevalence of male (20.73%) was higher than that of female (16.34%), and the difference was statistically significant ( P<0.001). The prevalence of Han nationality(17.31%) was higher than that of ethnic minorities (15.93%), and the difference was statistically significant ( P<0.001). Conclusion:The prevalence of allergic rhinitis in Chinese children is high and the prevalence in children varies by publication year, region, sex and nationality.

Objective:To analyze the prevalence of allergic rhinitis in Chinese children from 2001 to 2021, in order to provide data support for the prevention and treatment of allergic rhinitis in children.Methods:"Allergic rhinitis" "children" "adolescent" "infant" "prevalence" "epidemiology" were used in the main search terms. The combination of Mesh words and free words was adopted. CNKI, CBM, VIP, WanFang Data, PubMed, Web of Science, Embase and The Cochrane Library for publications between January 1, 2001 and December 31, 2021 were searched systemically and data were extracted from eligible studies by two independent reviewers. Supplementary collection was made by identifying retrospective references from the included literature. After study quality assessment, Meta analysis was completed using Stata 16.0 software.Results:A total of 20 cross-sectional studies were included, involving 54 886 cases. Meta analysis results showed that the overall prevalence of allergic rhinitis among the participants was 18.46% (95% CI:14.34%-22.59%). Subgroup analysis showed that the prevalence of allergic rhinitis from 2012 to 2021 (19.75%) was higher than that from 2001 to 2011 (14.81%), and the difference was statistically significant ( P<0.001). The prevalence of different regions from high to low was East China (22.77%), North China (20.82%), Northwest China (17.77%), Central China (16.62%), Southwest China (16.33%), Northeast China (16.16%) and South China (7.29%) respectively, the difference was statistically significant ( P<0.001). The prevalence of male (20.73%) was higher than that of female (16.34%), and the difference was statistically significant ( P<0.001). The prevalence of Han nationality(17.31%) was higher than that of ethnic minorities (15.93%), and the difference was statistically significant ( P<0.001). Conclusion:The prevalence of allergic rhinitis in Chinese children is high and the prevalence in children varies by publication year, region, sex and nationality.

The harm of pathogenic bacteria to humans has promoted extensive research on physiological processes of pathogens, such as the mechanism of bacterial infection, antibiotic mode of action, and bacterial antimicrobial resistance. Most of these processes can be better investigated by timely tracking of fluorophore-derived antibiotics in living cells. In this paper, we will review the recent development of fluorescent antibiotics featuring the conjugation with various fluorophores, and focus on their applica-tions in fluorescent imaging and real-time detection for various physiological processes of bacteria in vivo.

Src family kinase (SFK) highly expresses in many types of cancers,broadly adjusting their malignant behaviors.Paclitaxel is a widely used chemical agent.However,because of constant resistance,the effect of paclitaxel has been greatly attenuated.The present review summaries the recent research progress of the structure and adjustment of SFK and the molecular mechanism of paclitaxel resistance,as well as the regulation of SFK on paclitaxel resistance,in order to provide new references and evidences upon the paclitaxel-based tumor therapy.