Expansion of primary chondrocytes in two-dimensional monolayer culture causes progressive dedifferentiation and limits cartilage tissue engineering. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is primarily known as a secreted aggrecanase, but its intracellular role under cellular stress remains unclear. We propose that expansion-induced mechanical and oxidative stress redistributes ADAMTS4 to intracellular ribonucleoprotein complexes, where it suppresses HMOX1 post-transcriptionally. RNA sequencing after ADAMTS4 silencing, intracellular RNA immunoprecipitation sequencing, and interactome analysis collectively support an association between ADAMTS4 and HMOX1 RNA. ADAMTS4 may contact HMOX1 RNA directly as an unconventional RNA-binding protein or indirectly through canonical RNA-binding proteins, thereby weakening the Nrf2/HO-1 cytoprotective axis and accelerating dedifferentiation. This model links extracellular matrix remodeling to intracellular RNA regulation and suggests a dual function for ADAMTS4. If validated, it may provide new strategies for preserving the chondrocyte phenotype during expansion.

Chondrocytes play a pivotal role in cartilage tissue engineering. ADAMTS4 gene encodes aggrecanase-1, which is known to affect chondrocyte biology by regulating aggrecan degradation. However, the molecular mechanism by which ADAMTS4 regulates chondrocyte phenotype remains unclear. To comprehensively investigate Adamts4-regulated genes in primary rat costal chondrocytes, we conducted siRNA-mediated Adamts4 knockdown alongside RNA sequencing (RNA-seq), co-immunoprecipitation coupled with mass spectrometry (CO-IP/MS), and enhanced RNA immunoprecipitation sequencing (iRIP-seq). Our results demonstrated that Adamts4 knockdown did not affect chondrocyte apoptosis. However, Adamts4 silencing markedly changed the expression levels of numerous genes linked to cell differentiation and cell cycle progression. CO-IP/MS experiments showed that Adamts4 extensively interacted with RNA-binding proteins (RBPs) in rat chondrocytes. iRIP-seq data suggested that Adamts4 bound to a large number of transcripts, especially those with AU-rich motifs at coding regions. Most interestingly, we found three genes Hmox1, Acan, and Col2a1, which were deregulated upon Adamts4 silencing and enriched in the Adamts4 RIP samples. Altogether, these results indicate that Adamts4 knockdown remarkably modulates the transcriptomic profile of rat chondrocytes. Interactions with RBPs or target mRNAs might contribute to Adamts4-mediated alterations in gene expression. These findings warrant further investigation of the crucial target genes of ADAMTS4 in the regulation of human chondrocyte behaviors.

This case series study evaluates the effectiveness and safety of stapokibart in treating patients with refractory palmoplantar pustulosis.

The aim of this study was to review 120 cases of laryngeal cancer at the Department of Ears, Nose, and Throat (ENT) from 2010 to 2015 and to summarize and discuss the related symptoms and psychological nursing experience of patients with laryngeal cancer. The accumulation of experience and the continuous improvement in nursing techniques have focused on the nutritional aspects and psychosocial support of patients with larynx cancer. Providing systematic, comprehensive and individualized psychological and nutritional nursing interventions is critical for laryngeal cancer patients, and will promote rehabilitation, improve long-term quality of life, and increase patient satisfaction.

Obstructive sleep apnea (OSA) is manifested as periodic collapse of the upper airway during sleep. Otitis media is a spectrum of infectious and inflammatory diseases involving the middle ear. In this study, we sought to determine the causal effect of OSA on otitis media using a bidirectional, two-sample Mendelian randomization (MR) analysis. We analyzed the data from two different, extensive genome-wide association studies (GWAS) and selected OSA-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Bidirectional MR analysis was conducted using the inverse-variance weighted (IVW) method. To ensure the robustness of the results, alternative sensitivity analysis procedures were performed, including MR-Egger, the MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. In the forward MR analysis, OSA was correlated with an increased risk of acute suppurative otitis media (odds ratio, 1.164; 95% confidence interval, 1.056–1.283; P = 0.002) and suppurative and unspecified otitis media (odds ratio, 1.150; 95% confidence interval, 1.059–1.249; P < 0.001). All reverse MR analyses showed that otitis media had no causal effect on OSA (P > 0.05). The MR analysis supports that OSA contributes to the development of otitis media. Thus, managing OSA may be beneficial in treating otitis media.

Background: There is a lack of effective treatment for idiopathic unilateral vocal fold paralysis (IUVFP). A better phonation was reported by patients after laryngeal nerve stimulation during our clinical examination.Objectives: This study aims to investigate immediate effect of recurrent laryngeal nerve (RLN) stimulation on phonation in patients with IUVFP.Material and MethodsSixty-two patients with clinically identified IUVFP underwent RLN stimulation with needle electrodes. Laryngoscopy, acoustic analysis, and voice perception assessment were performed for quantitative comparison of vocal function and voice quality before and after the intervention.Results: Laryngoscopic images showed a larger motion range of the paralyzed vocal fold (p < .01) and better glottal closure (p < .01) after RLN stimulation. Acoustic analysis revealed that the dysphonia severity index increased significantly (p < .01) while the jitter and shimmer decreased after the intervention (p < .05). According to perceptual evaluation, RLN stimulation significantly increased RBH grades in patients with IUVFP (p < .01). Furthermore, the improvement in voice perception had a moderate positive correlation with the decrease in the glottal closure.Conclusions and Significance: This study shows a short-term improvement of phonation in IUVFP patients after RLN stimulation, which provides proof-of-concept for trialing a controlled delivery of RLN stimulation and assessing durability of any observed responses.

Objective:Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation. Methods:We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis. Results:More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST, PAX8-AS1, CASC15, LINC01618, and DLX6-AS1. The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation. Conclusions:We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation.

Background The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized. Methods This study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners. Results We found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration. Conclusions These findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.

Objectives:This study was designed to explore the relationship between Helicobacter pylori (Hp) infection and reflux laryngopharyngitis (RLP) and to evaluate the outcome of anti-Hp therapy in improving RLP symptoms.Methods:A total of 410 patients with RLP were enrolled and tested for Hp infection. The association of Hp infection with reflux symptom index (RSI) and reflux finding score (RFS) was determined. Hp-positive patients received either a proton pump inhibitor (PPI) omeprazole alone (control group) or a combination regimen (experimental group) consisting of omeprazole, mosapride citrate, amoxicillin, and clarithromycin. Therapeutic outcomes were compared 4 weeks later.Results:Of the 410 participants, 290 were Hp-positive and 120 Hp-negative. Both RSI and RFS were significantly higher in Hp-positive patients than in Hp-negative patients. Hp infection status was positively correlated with RSI (P < 0.05) and RFS (P < 0.05). The overall response rate was higher in the experimental group than in the control group. Both the groups had a significant reduction in RSI and RFS after therapy, with a greater improvement in the experimental group (P < 0.05).Conclusion:Our findings establish a link between Hp infection and RLP. Anti-Hp therapy improves RSI and RFS in RLP patients. Therefore, Hp eradication drugs may be added to the PPI-based regimen in the treatment of RLP.

Objective:To assess the efficacy and toxicity of nimotuzumab combined with neoadjuvant or induction che-motherapy for head and neck squamous cell carcinoma (HNSCC).Methods:Patients received intravenous nimo-tuzumab (400 mg, weekly for 1-3 weeks) combined with chemotherapy (5-fluorouracil/paclitaxel/docetaxel +nedaplatin/cisplatin for 1-2 cycles), prior to definitive surgical resection, radiotherapy or other treatments. Theprimary endpoint was the objective response rate (ORR). The secondary endpoints were tumor downstaging,complete response rate (CRR), partial response rate (PRR), disease control rate (DCR), R0 resection rate, patho-logical complete response (pCR), larynx preservation rate, overall survival (OS), progression-free survival (PFS),and safety.Results:A total of 71 HNSCC patients with T1-4N0-2M0were enrolled. After neoadjuvant/inductionchemotherapy, the ORR in patients with hypopharyngeal and laryngeal cancer was 100% and 76.1%, respectively.The DCR was 100% in both groups. The T downstaging in patients with hypopharyngeal and laryngeal cancerwas 64.0% and 50.0%, the N downstaging was 28.0% and 2.2% (p= 0.001), respectively. At the early stage andlocally advanced stage, the T downstaging was 66.7% and 50.0%, the N downstaging was 0% and 16.0% (p=0.128), respectively. The R0 resection rate and pCR in 39 patients receiving surgery were 94.9% and 20.5%, respec-tively. The larynx preservation rate was 73.2%. The median PFS was 29.2 months in patients with laryngeal can-cer. A mild rash occurred in a single patient and no grade 4 adverse events were encountered.Conclusion:Nimotuzumab combined with neoadjuvant or induction chemotherapy achieved similar short-term efficacyand less adverse events compared with previous studies. The N downstaging rate in patients with hypopharyngealcancer was significantly higher compared with patients with laryngeal cancer

目的 探讨TLR4/NF-κB通路在慢性鼻-鼻窦炎(CRS)伴鼻息肉(CRSwNP)和不伴鼻息肉(CRSsNP)的黏膜上皮修复机制中的作用.方法 收集2018年3月-2021年9月就诊于西安交通大学附属医院耳鼻咽喉科的30例CRS患者的鼻筛窦黏膜上皮组织.将CRS患者组织分为CRSsNP组和CRSwNP组,每组10例.对照组组织来源于进行视觉性鼻整形术的患者.HE染色、免疫组化法检测各组患者鼻黏膜组织病理学改变以及TLR4、NF-κB的表达;将各组鼻粘膜上皮细胞进行离体培养,分别以4种因素(空白对照组;EGF组:添加50 ml 5 ng/ml EGF;TLR4/NF-κB组:依次添加5 ng/ml TLR4和NF-κB培养24 h后,添加5 ng/ml EGF;PDTC组:添加5 ng/ml信号通路抑制剂PDTC培养12 h后,添加5 ng/ml TLR4和NF-κB培养12 h后,添加5 ng/ml EGF)刺激各组鼻粘膜上皮细胞,CCK-8法、ELISA检测各组鼻黏膜上皮细胞的增殖以及IL-β、1L-5的表达.结果 与CRSsNP组相比,CRSwNP组的鼻窦CT评分明显升高(P<0.05);与对照组患者相比,CRSsNP组、CRSwNP组TLR4、NF-κB的表达量升高(P<0.05);与CRSsNP组相比,CRSwNP组TLR4、NF-κB的表达量升高(P<0.05);CCK-8和ELISA法实验结果:与对照组相比,CRS组鼻粘膜上皮细胞的增殖基线降低,IL-β、IL-5的水平升高(P<0.05);与CRSsNP组相比,CRSwNP组鼻粘膜上皮细胞的增殖基线升高,IL-β、IL-5的水平升高(P<0.05);对照组和CRS组加入EGF后,与空白对照相比,鼻粘膜上皮细胞的增殖基线明显升高,IL-β、IL-5的水平降低(P<0.05);加入TLR4和NF-κB后,与空白对照相比,鼻粘膜上皮细胞的增殖基线降低,IL-β、IL-5的水平升高(P<0.05);加入PDTC后,EGF诱导细胞增值的作用明显有所恢复,IL-β、IL-5的水平明显有所降低(P<0.05).结论 TLR4/NF-κB信号通路影响CRS中CRSsNP和CRSwNP两者鼻粘膜上皮细胞损伤后的修复,抑制TLR4/NF-κB信号通路能明显增强CRS患者鼻粘膜上皮细胞的增殖作用.

目的 观察西吡氯铵含片联合PPI制剂治疗反流性咽喉炎的临床疗效.方法 本研究为回顾性研究,根据纳入及排除标准选取病例,比较PPI与PPI联合西吡氯铵的治疗效果.对照组共纳入102例,给予埃索美拉唑镁肠溶片治疗,晨起口服剂40mg 1次/d;观察组共纳入83例,给予埃索美拉唑镁肠溶片+西吡氯铵含片,前者剂量同对照组,后者剂量2mg,每日3次.在治疗4周和8周后,对比两组临床疗效,RSI及RFS.结果 两组的性别、年龄、病程、治疗前RSI和RFS无明显差异(P>0.05).治疗4周后及治疗8周后,观察组疗效较对照组疗效好(P=0.02,P=0.01).观察组治疗4周后、8周后RSI及RFS较对照组明显低(P=0.00,P=0.00).结论 PPI联合西吡氯铵对反流性咽喉炎的治疗作用相比单一应用PPI的效果更佳,在临床工作中值得推广和使用.

目的 探讨小钳口 LigaSure在腮腺深浅叶良恶性肿瘤切除术中的应用.方法 前瞻性的纳入西安交通大学第二附属医院耳鼻咽喉头颈外科病院2016年1月—2018年12月行腮腺来源肿瘤接受手术的47例患者,分为利用LigaSure切除(A组)27例及电刀结合传统刀片切除(B组)20例.对两组间的手术时间、术中出血量、术后48 h引流量及术后并发症进行比较.结果 A组的手术时间(85.56±43.94)min与B组(123.00±44.14)min相比,明显缩短(P＜0.05);两组术中出血量[(46.67±42.34)mLvs(75.00±49.92)mL]比较,差异具有统计学意义(P＜0.05);两组术后引流量[(38.15±17.16)mL vs(63.25±21.59)mL]比较,差异有统计学意义(P＜0.05);两组间术后并发症各参数无统计学差异.浅叶切除中A组和B组手术时间[(70.00±17.54)min vs(104.00±25.58)min],术中出血量[(33.81±21.79)mL vs(54.67±19.32)mL]及术后引流量[(32.62±11.36)mL vs(54.33±8.84)mL]比较,差异均具有统计学意义(P均＜0.05).腮腺全切(包括扩大切除)术中使用LigaSure的患者手术时间,术中出血量及术后引流量与对照组比较,差异均无统计学意义(P均＞0.05).结论 小钳口 LigaSure在切除腮腺良恶性肿瘤的应用是安全的,与传统手术方式相比尤其在浅叶手术中LigaSure有出血少,手术时间短等优势.

article: Effect of systemic rehabilitation nursing intervention on psychological status and postoperative recovery of laryngeal cancer patients in perioperative period - Minerva Medica 2022 December;113(6):1045-6 - Minerva Medica - Journals

目的:分析药物联合鼻内镜手术治疗变应性鼻炎(AR)伴鼻中隔偏曲的效果.方法:选取2017年1月—2019年11月我院收治的110例A R伴鼻中隔偏曲患者,随机分为单纯药物组(55例,枸地氯雷他定片+糠酸莫米松鼻喷雾剂)和药物手术联合组(55例,枸地氯雷他定片+糠酸莫米松鼻喷雾剂+鼻内镜下鼻中隔偏曲矫正术治疗),比较两组患者治疗效果、生活质量及1年复发率.结果:治疗后6、12个月两组生活质量评分均高于治疗前,且药物手术联合组生活质量评分高于单纯药物组,差异有统计学意义(P<0.05).药物手术联合组治疗总有效率高于单纯药物组,1年复发率低于单纯药物组,差异有统计学意义(P<0.05).结论:药物联合鼻内镜手术用于治疗AR伴鼻中隔偏曲患者效果显著,可在临床应用.

分析探讨分层培训模式在耳鼻咽喉头颈外科进修医师培养中的应用效果,为不断提高进修医师培养质量提供借鉴和参考.

Objective To determine the effect of personalized psychological interventions on the recovery of patients with sudden deafness. Methods Participants were 438 patients with sudden deafness who were randomly allocated to observation and control groups. Patients in the control group received routine nursing care and drug treatment. Patients in the observation group received personalized psychological interventions, routine nursing care and drug treatment. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) were used to measure anxiety and depression. The Simple Coping Style Questionnaire (SCSQ) and the Satisfaction With Life Scale (SWLS) were used to evaluate coping styles, attitude toward life and quality of life. Results Patients in both groups had similar SAS and SDS scores at the time of admission. After treatment, there was a significant difference in SAS and SDS scores between the observation and control groups, indicating that the observation group had less anxiety and depression. Both groups had increased SCSQ and SWLS scores following treatment, indicating improvements in positive coping and satisfaction with life. Conclusion Effective psychological interventions may change negative thoughts, increase response rate and improve quality of life.

Objective To compare the efficacy of two different treatment approaches for auricular pseudocyst. Methods This retrospective study reviewed data from patients with auricular pseudocyst that were treated with either anterior wall resection plus radiofrequency ablation compression (surgical group) or simple aspiration and compression suturing (control group). The following outcomes were compared between the two groups: therapeutic response (cure, good or none), duration of postoperative medication (antibiotics) use, duration of postoperative pain, duration of recovery of appearance and rate of complications (infection, auricular thickening, incision swelling and recurrence). Results A total of 386 patients were enrolled in the study: 218 in the surgical group and 168 in the control group. Duration of postoperative medication use, duration of postoperative pain, duration of recovery of appearance and rate of postoperative complications were significantly lower in the surgical group compared with the control group. The overall therapeutic response (cure and good response) was significantly greater in the surgical group than in the control group. Conclusion Auricular pseudocyst can be effectively treated by both of these methods, but anterior wall resection plus radiofrequency ablation compression might be more effective.

Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients. Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

Objective Previous studies have shown that patients with obstructive sleep apnea syndrome (OSAS) may have various vestibular abnormalities, and these mainly present as subclinical lesions. In this study, we attempted to combine ocular vestibular-evoked myogenic potentials (VEMPs) and cervical (VEMPs) to investigate vestibular dysfunction in patients with OSAS. Methods Thirty-eight patients with severe OSAS and 42 healthy controls were enrolled and divided into two groups according to results of polysomnography. All parameters of VEMP graphs were analyzed. Results The response rate of ocular VEMPs was significantly lower in patients with severe OSAS (85.5%) than in controls (96.4%). The mean n1 latency of patients with severe OSAS (10.6 ± 1.0 months) was significantly longer than that of controls (10.2 ± 1.1 months). With regard to cervical VEMP, p1-n1 amplitudes were significantly different between the groups. Other VEMP parameters were not significantly different between the groups. Conclusions VEMPs can potentially be used to evaluate vestibular system lesions at the early stage of OSAS, including not only the vestibular nerve, but also the otolith organs involved.