Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4+ T cells. The loss of TFEB in Treg cells leads to reduced Treg accumulation and impaired Treg function in mouse models of cancer and autoimmune disease. TFEB intrinsically regulates genes involved in Treg cell differentiation and mitochondria function while it suppresses expression of proinflammatory cytokines independently of its established roles in autophagy. This coordinated action is required for mitochondria integrity and appropriate lipid metabolism in Treg cells. These findings identify TFEB as a critical regulator for orchestrating Treg generation and function, which may contribute to the adaptive responses of T cells to local environmental cues.

Organic Fluorophores with Large Stokes Shift for the Visualization of Rapid Protein and Nucleic Acid Assays.

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).

A Novel Cell Membrane-Associated RNA Extraction Method and Its Application in the Discovery of Breast Cancer Markers.

Cell membrane-associated RNA (mem-RNA) has been demonstrated to be cell-specific and disease-related and are considered as potential biomarkers for disease diagnostics, drug delivery, and cell screening. However, there is still a lack of methods specifically designed to extract mem-RNA from cells, limiting the discovery and applications of mem-RNA. In this study, we propose the first all-in-one solution for high-purity mem-RNA isolation based on two types of magnetic nanoparticles, named MREMB (Membrane-associated RNA Extraction based on Magnetic Beads), which achieved ten times enrichment of cell membrane components and over 90% recovery rate of RNA extraction. To demonstrate MREMB's potential in clinical research, we extracted and sequenced mem-RNA of typical breast cancer MCF-7, MDA-MB-231, and SKBR-3 cell lines and non-neoplastic breast epithelial cell MCF-10A. Compared to total RNA, sequencing results revealed that membrane/secreted protein-encoding mRNAs and long noncoding RNAs (lncRNAs) were enriched in the mem-RNA, some of which were significantly overexpressed in the three cancer cell lines, including extracellular matrix-related genes COL5A1 and lncRNA TALAM1. The results indicated that MREMB could enrich membrane/secreted protein-coding RNA and amplify the expression differences of related RNAs between cancer and non-neoplastic cells, promising for cancer biomarker discovery.

SIRT3/GLUT4 signaling activation by metformin protect against cisplatin-induced ototoxicity in vitro.

Cisplatin is highly effective for killing tumor cells. However, as one of its side effects, ototoxicity limits the clinical application of cisplatin. The mechanisms of cisplatin-induced ototoxicity have not been fully clarified yet. SIRT3 is a deacetylated protein mainly located in mitochondria, which regulates a variety of physiological processes in cells. The role of SIRT3 in cisplatin-induced hair cell injury has not been founded. In this study, primary cultured cochlear explants exposed to 5 µM cisplatin, as well as OC-1 cells exposed to 10 µM cisplatin, were used to establish models of cisplatin-induced ototoxicity in vitro. We found that when combined with cisplatin, metformin (75 µM) significantly up-regulated the expression of SIRT3 and alleviated cisplatin-induced apoptosis of hair cells. We regulated the expression of SIRT3 to explore the role of SIRT3 in cisplatin-induced auditory hair cell injury. Overexpression of SIRT3 promoted the survival of auditory hair cells and alleviated the apoptosis of auditory hair cells. In contrast, knockdown of SIRT3 impaired the protective effect of metformin and exacerbated cisplatin injury. In addition, we found that the protective effect of SIRT3 may be achieved by regulating GLUT4 translocation and rescuing impaired glucose uptake caused by cisplatin. Our study confirmed that upregulation of SIRT3 may antagonize cisplatin-induced ototoxicity, and provided a new perspective for the study of cisplatin-induced ototoxicity.

The PERK/ATF4/CHOP signaling branch of the unfolded protein response mediates cisplatin-induced ototoxicity in hair cells.

Cisplatin is a widely used chemotherapeutic agent. However, its clinical application remains limited due to the high incidence of severe ototoxicity. It has been reported that the unfolded protein response (UPR) is involved in cisplatin-induced ototoxicity. However, the specific mechanism underlying its effect remains unclear. Therefore, the present study aimed to explore the sequential changes in the key UPR signaling branch and its potential pro-apoptotic role in cisplatin-induced ototoxicity. The hair cell-like OC-1 cells were treated with cisplatin for different periods and then the expression levels of the UPR- and apoptosis-related proteins were determined. The results showed that the apoptotic rate of cells was gradually increased with prolonged cisplatin treatment. Furthermore, the sequential changes in three UPR signaling branches were evaluated. The expression levels of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were gradually increased with up to 12 h of cisplatin treatment. The aforementioned expression profile was consistent with that observed for the apoptosis-related proteins. Subsequently, the proportion of apoptotic cells was notably decreased in CHOP-silenced hair cell-like OC-1 cells following treatment with cisplatin. Moreover, we found significant hair cells loss and a higher level of CHOP in cisplatin-treated cochlear explants in a time-dependent manner. Overall, the present study demonstrated that the protein kinase RNA­like endoplasmic reticulum kinase (PERK)/ATF4/CHOP signaling branch could play an important role in cisplatin-induced cell apoptosis. Furthermore, the current study suggested that CHOP may be considered as a promising therapeutic target for cisplatin-induced ototoxicity.

Effects of early cognitive rehabilitation training on cognitive function and quality of life in critically ill patients with cognitive impairment: A randomised controlled trial.

BACKGROUND: Patients often develop cognitive dysfunction during admission to the ICU and after being transferred out of the ICU, which leads to physical disorders, sleep disorders, and psychological stress.Cognitive rehabilitation training can significantly improve patients' planning, decision-making ability, and executive function. OBJECTIVE: The aim of this study was to explore the role of early cognitive rehabilitation training in improving cognitive impairment in critically ill patients. METHODS: This study was a prospective, randomised, controlled clinical trial conducted from January 2017 to June 2021. Critically ill patients with cognitive impairment admitted to the Department of Intensive Care Medicine of The Third Hospital of Mianyang were randomly divided into the control (n = 68) and intervention groups (n = 68). Cognitive rehabilitation training (including digital operating system training, music therapy, aerobic training, and mental health intervention) was applied to the patients in the intervention group for 6 months, while the control group did not receive any cognitive intervention. Before 3 and 6 months after enrolment, the Montreal Cognitive Assessment and the 36-Item Short Form Health Survey Scale were used to evaluate cognitive function and quality of life, respectively, in both groups. RESULTS: A total of 136 critical patients were included in the final analysis. There were no significant differences in sex, age, years of education, complications, intensive care unit hospitalisation time, mechanical ventilation time, or the total score of the Montreal Cognitive Assessment scale when transferred out of the intensive care unit in 24 hours between the two groups. Six months later, the results of the follow-up showed that the cognitive function score in the intervention group was significantly higher than that in the control group (26.69 ± 2.49 vs. 23.03 ± 3.79). The analysis of quality of life showed that the scores in all areas in the intervention group improved. There were significant differences in physical functioning (69.02 ± 8.14 vs. 63.38 ± 11.94), role physical (62.02 ± 12.18 vs. 58.09 ± 8.83), general health (46.00 ± 15.21 vs. 40.38 ± 13.77), vitality (61.00 ± 11.01 vs. 54.38 ± 13.80), social functioning (70.00 ± 10.29 vs. 64.41 ± 13.61), role emotional (78.00 ± 8.00 vs. 72.15 ± 12.18), and mental health (71.00 ± 12.33 vs. 55.37 ± 10.76) between the two groups (P < 0.05). CONCLUSION: Early cognitive rehabilitation training can improve cognitive impairment in critically ill patients and their quality of life.

Association of plasma lead, cadmium and selenium levels with hearing loss in adults: National Health and Nutrition Examination Survey (NHANES) 2011-2012.

To determine the association between hearing loss and environmental Pb, Cd and Se exposure, a total of 1503 American adults from National Health and Nutrition Examination Survey (NHANES) (2011-2012) were assessed. The average of four audiometric frequencies (0·5, 1, 2 and 4 kHz) was used to identify speech-frequency hearing loss (SFHL), while the average of 3 audiometric frequencies (3, 4 and 6 kHz) was used to identify high-frequency hearing loss (HFHL). HFHL adjusted OR determined by comparing the highest and lowest blood Pb and Cd quartiles were 1·98 (95 % CI: 1·27, 3·10) and 1·81 (95 % CI: 1·13, 2·90), respectively. SFHL was significantly associated with blood Cd with the OR = 2·42 for the highest quartile. When further stratified by age, this association appeared to be limited to adults aged 35-52 years. After stratified by gender, except for Pb and Cd, we observed that blood Se showed a dose-dependent association with SFHL in men. In women, only Cd showed a dose-dependent association with speech and high-frequency hearing loss. Hearing loss was positively associated with blood levels of Pb and Cd. Additionally, our study provided novel evidence suggesting that excessive Se supplement would increase SFHL risk in men.

Periostin deficiency reduces diethylnitrosamine-induced liver cancer in mice by decreasing hepatic stellate cell activation and cancer cell proliferation.

Periostin is a critical extracellular regulator in the pathogenesis of liver disorders such as hepatosteatosis, non-alcoholic steatohepatitis, inflammation, and fibrosis. Periostin is also involved in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms of periostin in hepatic stellate cell (HSC) activation and tumor cell proliferation in the pathogenesis of HCC remain largely unknown. We demonstrate that periostin is markedly upregulated in diethylnitrosamine (DEN)-induced mouse HCC tissues and that periostin knockout impairs DEN-induced HCC development. Periostin is predominantly derived from activated HSCs and periostin deficiency in HSCs impairs HSC activation and inhibits HSC-promoted HCC cell proliferation in vitro and tumor growth in vivo. Mechanistically, periostin promotes HSC activation through the integrin-FAK-STAT3-periostin pathway and augments HCC cell proliferation by activating ERK. There are positive correlations between periostin and HSC activation and cell proliferation in HCC clinical samples. Collectively, our findings demonstrate that HSC-derived periostin promotes HCC development by enhancing HSC activation through an autocrine periostin-integrin-FAK-STAT3-periostin circuit and by augmenting HCC cell proliferation via the ERK pathway in a paracrine manner. Thus, periostin is a multifaceted extracellular regulator in the development of HCC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

miRNA biomarkers for predicting overall survival outcomes for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract. The loss and gain of miRNA function promote cancer development through various mechanisms. RNA sequencing (RNA-seq) and miRNAs sequencing data from the Cancer Genome Atlas (TCGA) was used to show the dysfunctional miRNAs microenvironment and to provide useful biomarkers for miRNAs therapy. Seven miRNAs were found to be independent prognostic factors of HNSCC patients in the training cohort. A total of 60 target genes for these miRNAs were predicted. Nine target genes (CDCA4, CXCL14, FLNC, KLF7, NBEAL2, P4HA1, PFKM, PFN2 and SEPPINE1) were correlated with patient's overall survival (OS) outcomes. We identified novel miRNAs markers for the prognosis of head and neck squamous cell carcinoma.

Effect of wearing personal protective equipment on acoustic characteristics and speech perception during COVID-19.

With the COVID-19 pandemic, the usage of personal protective equipment (PPE) has become 'the new normal'. Both surgical masks and N95 masks with a face shield are widely used in healthcare settings to reduce virus transmission, but the use of these masks has a negative impact on speech perception. Therefore, transparent masks are recommended to solve this dilemma. However, there is a lack of quantitative studies regarding the effect of PPE on speech perception. This study aims to compare the effect on speech perception of different types of PPE (surgical masks, N95 masks with face shield and transparent masks) in healthcare settings, for listeners with normal hearing in the audiovisual or auditory-only modality. The Bamford-Kowal-Bench (BKB)-like Mandarin speech stimuli were digitally recorded by a G.R.A.S KEMAR manikin without and with masks (surgical masks, N95 masks with face shield and transparent masks). Two variants of video display were created (with or without visual cues) and tagged to the corresponding audio recordings. The speech recording and video were presented to listeners simultaneously in each of four conditions: unattenuated speech with visual cues (no mask); surgical mask attenuated speech without visual cues; N95 mask with face shield attenuated speech without visual cues; and transparent mask attenuated speech with visual cues. The signal-to-noise ratio for 50 % correct scores (SNR50) threshold in noise was measured for each condition in the presence of four-talker babble. Twenty-four subjects completed the experiment. Acoustic spectra obtained from all types of masks were primarily attenuated at high frequencies, beyond 3 kHz, but to different extents. The mean SNR50 thresholds of the two auditory-only conditions (surgical mask and N95 mask with face shield) were higher than those of the audiovisual conditions (no mask and transparent mask). SNR50 thresholds in the surgical-mask conditions were significantly lower than those for the N95 masks with face shield. No significant difference was observed between the two audiovisual conditions. The results confirm that wearing a surgical mask or an N95 mask with face shield has a negative impact on speech perception. However, wearing a transparent mask improved speech perception to a similar level as unmasked condition for young normal-hearing listeners.

The prognostic significance of survivin expression in patients with HNSCC: a systematic review and meta-analysis.

BACKGROUND: Survivin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here we conducted a comprehensive meta-analysis to better clarify they the precise prognostic and diagnostic value of survivin in head and neck squamous cell carcinoma (HNSCC). METHODS: Database of PubMed (Medline), Embase, and Web of Science were systematically searched for related published literature up to September 2020. Pooled hazards ratios (HR) and related 95% confidence intervals (CI) were used to estimate the association of survivin expression and survival outcomes in HNSCC patients. RESULTS: Twenty eight studies with 4891 patients were finally included in this meta-analysis, the pooled analysis indicated that the survivin expression was significantly correlated with poorer overall survival (OS) (HR, 2.02; 95% CI, 1.65-2.47, P < 0.001), and poorer disease-free survival (DFS)/ disease-specific survival (DSS) (HR = 2.03, 95%CI: 1.64-2.52, P < 0.001; HR = 1.92, 95%CI: 1.41-2.60, P < 0.001, receptively). Similar results were observed in subgroup analysis stratified by different cancer types, such as laryngeal squamous cell carcinoma (LSCC) (HR = 1.35, 95%CI: 1.05-1.74, P < 0.001), oral squamous cell carcinomas (OSCC) (HR = 2.45, 95%CI: 1.89-3.17, P < 0.001), nasopharyngeal carcinoma (NPC) (HR = 2.53, 95%CI: 1.76-3.62, P < 0.001) and HNSCC (HR = 1.52, 95%CI: 1.25-1.86, P < 0.001). Furthermore, ethnicity-stratified analysis indicated that survivin was significantly associated with poorer OS among both Asian and Non- Asian HNSCC patients (HR = 2.16, 95%CI: 1.76-2.66; HR = 1.56, 95%CI: 1.33-1.82, respectively). CONCLUSIONS: Our results suggested that survivin is predictors of worse prognosis in HNSCC patients. Hence, survivin is a potential therapeutic target for HNSCC.

The expression profiles and prognostic values of HSPs family members in Head and neck cancer.

BACKGROUND: Head and neck squamous cell carcinoma (HNSC) ranks as the sixth most common malignancy. The identification of highly specific and sensitive prognostic markers and potential drug targets can contribute to enhanced patient prognosis and individualized treatments. Heat shock proteins (HSPs) act as molecular chaperones and play a crucial role in maintaining cell homeostasis. Recently, research has indicated that HSPs also act as "evil chaperones" in cancer development. METHODS: In this study, we assessed the expression of HSPs in HNSC patients using the ONCOMINE, GEPIA, and UALCAN databases. Mutations of HSP genes were also analysed using the cBioPortal database. Additionally, the expression levels of HSPs were verified using the Human Protein Altas (THPA) database. RESULTS: We found that the expression levels of HSPH1, HSPD1, SERPINH1, HSPA4, and HSP90AA1 were significantly higher in tissues from HNSC patients compared with normal tissues. Moreover, HSPH1, HSPD1, SERPINH1, HSPA4 and HSP90AA1 expressions were linked to disease progression. Survival analysis with the GEPIA and OncoLnc databases indicated that upregulation of HSPH1, HSPD1, SERPINH1, HSPA4 and HSP90AA1 was related to poor overall survival (OS). CONCLUSION: This study suggests that the HSPH1, HSPD1, SERPINH1, HSPA4 and HSP90AA1 genes are potential clinical targets and prognostic biomarkers for patients with HNSC.

Bilayer Adsorption of Porphyrin Molecules Substituted with Carboxylic Acid atop the NN4A Network Revealed by STM and DFT.

Bottom-up technology is a bridge connecting a two-dimensional (2D) monolayer structure with a three-dimensional (3D) bulk structure. From 2D to 3D, it helps us to understand the driving force of an organization process to control the molecular arrangement in the 3D phase. Here, we aimed at the fabrication of multilayer nanostructures on solid substrates. Bis(3,5-diacidic)diazobenzene (NN4A) was chosen as one molecule because of its photosensitive azo group and carboxylic group possessing hydrogen bonding effect, while porphyrin molecules composed of different numbers and positions of carboxylic acid groups were used as the other component. It was found that the porphyrin molecules could adopt different adsorption configurations because of the influence of carboxylic groups, leading to different subsequent coassemblies on the solid surface. The NN4A/porphyrin systems underwent structural transformation when NN4A molecules were adsorbed on the highly oriented pyrolytic graphite surface with predeposited porphyrin. This work displayed an efficient method on the construction of multilayer nanostructures in the molecular surface engineering and provided a new way to construct 3D structures based on the molecular design.

Surface Separation and in Situ Structural Regulation of Photosensitive Oligomer in a Flexible Template.

Surface-selective adsorption and separation are very important for the application of surface functional materials. In this study, a photosensitive diazo-macrocycle has been synthesized by the solvent method with a very low yield, which can adsorb onto the substrate surface modified with a template molecule. By using this flexible template on the graphite surface, a simple separation strategy for the macrocyclic molecule with specific shape and size from reaction mixtures was developed. Additionally, one of the two azo units in this trapped photosensitive macrocycle could convert from trans to cis conformation under UV irradiation due to the steric effect. Our results provide a new way to construct functional nanodevices using a surface flexible template as the separation and regulation medium.

Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model.

Endoplasmic reticulum (ER) stress arises when excessive improperly folded proteins accumulate in the ER lumen. When ER stress occurs, the unfolded protein response (UPR) is subsequently activated to restore ER proteostasis. However, severe ER stress leads to apoptosis. Recent studies have suggested that cisplatin cytotoxicity may be related to ER stress. The purpose of this study was to determine whether ER stress participates in cochlear cell apoptosis in a cisplatin-induced ototoxicity rat model and to also determine the possible relationship between ER stress and hearing loss. Our results revealed that treatment with cisplatin upregulated the expression of active caspase-12 in cochlear cells, which is indicative of cisplatin-induced activation of ER-specific apoptosis. Increased expression of C/EBP homologous protein (CHOP) and cleaved caspase-9 suggested a close relationship between severe ER stress and mitochondria-dependent apoptosis in the cochlear cells of cisplatin-treated rats. In addition, we found that tauroursodeoxycholic acid (TUDCA), a promoter of ER proteostasis, had a protective effect on cisplatin-induced hearing loss. These results demonstrate that ER stress is involved in the cisplatin-induced apoptosis of cochlear cells in vivo.

Matricellular protein periostin contributes to hepatic inflammation and fibrosis.

Periostin actively contributes to tissue injury, fibrosis, atherosclerosis, and inflammatory diseases; however, its role in hepatic fibrosis is unclear. Herein, we revealed that periostin expression was significantly up-regulated in carbon tetrachloride- and bile duct ligation-induced mice with acute and chronic liver fibrosis. Deficiency in periostin abrogated the development of liver fibrosis in mice. Carbon tetrachloride treatment significantly increased α-smooth muscle actin, fibronectin, and collagen I levels in wild-type mice, which were unaffected in periostin-knockout mice. Periostin-deficient mice showed a significantly reduced area of collagen deposition and decreased levels of serum alanine aminotransferase and aspartate aminotransferase compared with wild-type mice after 2 weeks of carbon tetrachloride administration. Chemokine ligand 2, IL-6, IL-1ß, tumor necrosis factor-α, and tissue inhibitor of metalloproteinases 1 mRNA levels were significantly lower in periostin-deficient mice than in wild-type mice after carbon tetrachloride treatment. Periostin colocalized with hepatic stellate cell-derived collagen I and α-smooth muscle actin in mouse acute and chronic fibrotic liver tissues. Transforming growth factor (TGF)-ß1 markedly induced periostin expression in primary mouse hepatic stellate cells. Periostin-deficient mice showed significantly lower levels of TGF-ß1 and TGF-ß2 compared with wild-type mice after carbon tetrachloride treatment. High levels of periostin in patients with acute or chronic hepatitis correlated with TGF-ß1 and TGF-ß2 expression in serum from patients with hepatitis. Data indicate that periostin is a novel mediator of hepatic fibrosis development.

Rapamycin alleviates cisplatin-induced ototoxicity in vivo.

BACKGROUND: Cisplatin-induced ototoxicity affects a high percentage of new cancer patients worldwide. The detailed mechanism of cisplatin-induced ototoxicity is not completely understood. We investigated whether rapamycin could protect rats from cisplatin-induced ototoxicity. METHODS: Forty-eight male Wistar rats were randomly divided into six groups. Three groups were intraperitoneally (IP) infused with cisplatin at a dose of 16 mg/kg and immediately injected with either dimethylsulfoxide (DMSO), rapamycin, or chloroquine (CQ). The remaining three groups were treated with rapamycin, CQ, or saline alone. The auditory brainstem response (ABR) test was performed to detect the rats' hearing status. Serum was isolated to measure the level of the oxidative marker malondialdehyde (MDA), the basilar membrane was prepared to count the outer hair cell loss, and soft tissue samples extracted from the cochleae were lysed to analyze the microtubule-associated protein light chain 3 (LC3) and Beclin-1. RESULTS: The rapamycin treatment significantly attenuated cisplatin-induced hearing loss, decreased oxidative stress, and alleviated the hair cell damage that was associated with the upregulation of the LC3-II/GAPDH ratio and increased Beclin-1 expression. CONCLUSION: Our results demonstrated that rapamycin has an otoprotective effect; it attenuates cisplatin-induced ototoxicity, probably by attenuating oxidative damage and inducing autophagy.

Endoscopic vidian and vidian-branch neurectomy for refractory allergic rhinitis: A systematic review.

BACKGROUND: Endoscopic vidian neurectomy is expected to provide good therapeutic relief in patients with allergic rhinitis (AR) being refractory to medication therapy or conservative surgery. However, the evidence bases for its benefit remain debatable. In this study, we conducted a systematic review and meta-analysis to clarify the therapeutic role of various forms of vidian neurectomy in refractory AR. METHOD: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct a systematic review of primary studies that reported original patient data for endoscopic vidian neurectomy (EVN) and vidian-branch neurectomy, which includes selective vidian neurectomy (SVN) and posterior nasal neurectomy (PNN). The primary outcome was patient-reported outcome measures (PROMs), including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Visual Analog Scale (VAS), to assess an improvement in nasal symptom severity and quality of patient's life. The incidence of surgical complications and other objective outcomes were considered secondary outcomes. RESULTS: This review included 24 clinical studies involving 1677 patients with refractory AR, of which 510 patients in six studies had combined chronic rhinosinusitis with nasal polyps (CRSwNP) and 95 patients in one study had combined asthma. Postoperative PROMs were significantly better than preoperatively in almost all patients who underwent vidianp (RQLQ: standardized mean difference [SMD] = 2.66, 95% confidence interval [CI] = 2.40-2.92, p < 0.001; VAS: SMD = 5.15, 95% CI = 4.29-6.02, p < 0.001) or vidian-branch neurectomy (RQLQ in PNN: SMD = 3.29, 95% CI = 2.45-4.13, p < 0.001; VAS in PNN: SMD = 4.38, 95% CI = 3.41-5.34, p < 0.001), and were generally better than in the conservative treatment group. Dividing with 18 months as the cutoff point, a subgroup analysis of the follow-up period was conducted, and the results showed that both long-term and short-term postoperative patients had considerably reduced symptoms compared to the preoperative period. The two surgical procedures, SVN and PNN, attributed to vidian-branch neurectomy have extremely few complications. However, EVN is more likely to cause dry eyes and palatal numbness, with no other serious complications. In patients with AR and CRSwNP, vidian or selective vidian neurectomy combined with functional endoscopic sinus surgery (FESS) is more effective than conventional FESS (RQLQ: SMD = 2.17, 95% CI = 1.66-2.69, p < 0.001; VAS: SMD = 6.42, 95% CI = 4.78-8.06, p < 0.001). For patients who have both AR and asthma, SVN with pharyngeal branch excision is a potential treatment option. CONCLUSION: EVN and vidian-branch neurectomy (including SVN and PNN) are effective treatments, but the former has a higher risk of complications. Additionally, vidian-branch neurectomy with FESS is beneficial for patients with mixed CRSwNP. SVN is a potential approach for patients with coexisting AR and asthma.

Allergy in pathogenesis of Eustachian Tube Dysfunction.

Eustachian tube dysfunction (ETD) is a condition where the Eustachian tube (ET) fails to function normally, resulting in symptoms such as aural fullness, tinnitus, autophony, and hearing loss. ETD can further lead to middle ear diseases such as otitis media effusion and adhesive otitis media, which is becoming more common in the field of otology. Although the pathogenesis of ETD remains unclear, recent animal studies and clinical experiments have found allergic reactions and allergic diseases are closely related to the occurrence of ETD. As the mucosa of the ET is continuous with that of the nasopharynx and tympanic cavity, it is reasonable to assume that the immunological basis of the ET itself is similar to that of respiratory allergic diseases. However, due to the special anatomical location and complex pathogenesis of the ET, there is still no unified diagnostic gold standard. Additionally, there is an ongoing debate regarding whether ETD can be classified as a distinct disease or even an allergic disease. Furthermore, the effectiveness of anti-allergic therapy in patients with ETD is yet to be fully understood. Therefore, this review elaborates on the possible mechanisms of allergic reactions in the occurrence and development of ETD, and explores the potential role of anti-allergic therapy in managing this condition, in order to provide new insights into the pathogenesis and prevention of ETD.