[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Case Reports of Low-Temperature Plasma Radiofrequency Treatment for Congenital Epiglottic Cysts in Neonates and Infants.

An uncommon benign condition in neonates, known as congenital epiglottic cyst, can lead to symptoms such as neonatal dyspnea, laryngeal stridor, and, in severe cases, even pose a potential threat of asphyxia-related mortality. A congenital epiglottic cyst is one of the neonatal emergencies. Fibrolaryngoscopy is the predominant method of diagnosis, and early identification, diagnosis, as well as treatment are the key points. Successful endoscopic ablation of congenital epiglottic cysts in 3 newborns was achieved through the utilization of a low-temperature plasma radiofrequency ablation system. Consequently, the purpose of this case report is to assist pediatric emergency physicians in the timely identification of congenital epiglottic cysts with the potential risk of mortality and to provide additional experience in clinical management.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Spontaneous Cerebrospinal Fluid Rhinorrhea in a Patient With Breast Cancer.

Despite the well documented increased risk of osteopenia in patients with breast cancer during chemotherapy and endocrine therapy, spontaneous cerebrospinal fluid rhinorrhea (CSFR) is still rare. The authors present a case of spontaneous CSFR that occurred during chemotherapy and endocrine therapy for breast cancer. The patient underwent a repair using myofascia and adipose tissue and was started on mannitol. There was no recurrence at 1-year follow-up. Therefore, clinicians should pay attention to the possibility of CSFR in patients with breast cancer, to avoid misdiagnosis.

Multi-omics characterization of a scoring system to quantify hypoxia patterns in patients with head and neck squamous cell carcinoma.

BACKGROUND: The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remains < 50%. Hypoxia patterns are a hallmark of HNSCC that are associated with its occurrence and progression. However, the precise role of hypoxia during HNSCC, such as the relationship between hypoxia, tumor immune landscape and cell communication orchestration remains largely unknown. The current study integrated data from bulk and single-cell RNA sequencing analyses to define the relationship between hypoxia and HNSCC. METHODS: A scoring system named the hypoxia score (HS) was constructed based on hypoxia-related genes (HRGs) expression. The predictive value of HS response for patient outcomes and different treatments was evaluated. Single-cell datasets and cell communication were utilized to rule out cell populations which hypoxia targeted on. RESULTS: The survival outcomes, immune/Estimate scores, responses to targeted inhibitors, and chemotherapeutic, and immunotherapy responses were distinct between a high HS group and a low HS group (all P < 0.05). Single-cell datasets showed different distributions of HS in immune cell populations (P < 0.05). Furthermore, HLA-DPA1/CD4 axis was identified as a unique interaction between CD4 + T Conv and pDC cells. CONCLUSIONS: Altogether, the quantification for hypoxia patterns is a potential biomarker for prognosis, individualized chemotherapeutic and immunotherapy strategies. The portrait of cell communication characteristics over the HNSCC ecosystem enhances the understanding of hypoxia patterns in HNSCC.

A comprehensive overview of emerging techniques and chemometrics for authenticity and traceability of animal-derived food.

Authenticity and origin tracing of animal-derived food are particularly necessary due to various kinds of food fraud such as adulteration, counterfeiting, substitution and intentional mislabeling. This review focuses on the current research status of animal-derived food from the aspects of geographical origin, feeding ingredients and systems, adulteration of substitutes, and physical and chemical properties. The methods and statistical models involved in the research and their advantages and disadvantages are summarized. Stable isotope ratio analysis and element analysis are the most extensive used geographical traceability techniques. Spectroscopic techniques have the advantages of quick response, low cost and non-destructiveness. Instrument technology combined with chemometrics is the key method for origin traceability and authenticity of animal-derived food. In addition, there is a new trend of origin traceability by analyzing inedible parts of animal-derived food. This review intends to give a broad but comprehensive understanding in authenticity and geographical origin traceability of animal-derived food.

GAPDH: unveiling its impact as a key hypoxia-related player in head and neck squamous cell carcinoma tumor progression, prognosis, and therapeutic potential.

Head and neck squamous cell carcinoma (HNSCC), characterized by hypoxia patterns, ranks as the sixth most prevalent malignant tumor worldwide. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a role in oncogenesis under hypoxic conditions in various cancers. However, its precise function in HNSCC, especially under varied hypoxic conditions, including at high altitudes, remains unclear. Elevated GAPDH mRNA and protein levels in HNSCC relative to normal tissues have been demonstrated through data from The Cancer Genome Atlas (TCGA), GSE29330, and the Human Protein Atlas (P<0.05). This elevation was further confirmed through in vitro experiments utilizing two HNSCC cell lines and a normal oral mucosal epithelial cell line. Additionally, data from TCGA and GSE41613 reveal a correlation between elevated GAPDH expression and diminished overall and progression-free survival in patients (P<0.05). Subsequent analysis identifies GAPDH as an independent risk factor for HNSCC (P<0.05). Using the ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) algorithms, high GAPDH expression was found to be associated with reduced immune scores and diminished anti-tumor cell infiltration, such as CD8+ T cells, in TCGA and GSE41613 datasets (P<0.05). Analysis of single-cell RNA sequencing data from GSE139324 suggests that elevated GAPDH expression hinders communication between plasmacytoid dendritic cells and mast cells (P<0.05). Furthermore, in the TCGA and GSE41613 datasets, GAPDH's biological function is closely tied to hypoxia through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA) analyses. Moreover, its expression is linked to one cuproptosis-related gene, five N6-methyladenosine-related genes, six immune checkpoint genes, and pivotal pathways such as MYC and E2F (P<0.05). GAPDH showed excellent predictive value in estimating the efficacy of immunotherapy and 11 anti-tumor drugs (e.g., cisplatin) (P<0.05), using TIDE and pRRophetic algorithms on the TCGA and GSE41613 datasets. Under 1% O2 in vitro, HNSCC cells show elevated GAPDH expression, leading to decreased apoptosis and increased migration, clonogenicity, invasiveness, and resistance to cisplatin (P<0.05). At 5% O2, these effects persisted, albeit less pronouncedly. Inhibiting GAPDH reversed these effects under all oxygen concentrations (P<0.05). Overall, our findings reveal GAPDH as a key hypoxia-related player influencing tumor progression, prognosis, and therapeutic potential in HNSCC.

EPHB2 as a recurrence-related gene and a prognostic indicator in nasopharyngeal carcinoma: A bioinformatics screening and immunohistochemistry verification.

Recurrence and metastasis of nasopharyngeal carcinoma (NPC) after radical treatment is a major bottleneck in clinical treatment. Therefore, we aimed to find the genes related to metastasis after radical treatment in NPC patients. Public datasets in the Gene Expression Omnibus database were consulted and the differential expression genes (DEGs) were screened out. The possible roles of the DEGs were annotated by Gene Ontology, and pathway analysis. The hub genes/proteins were then filtered out through protein-protein interaction network construction. The key genes were sifted out from the hub genes, and their expressions were verified by qPCR and immunohistochemistry assays. A total of 28 DEGs were filtered out, which may be enriched in different signaling pathways. Of these DEGs, 11 hub genes were filtered out, among which EPHB2 was shown to be over-expressed in NPC tissues. Further experimental assays confirmed that EPHB2 was overexpressed in NPC cells, which might be associated with tumor recurrence, neck lymph node metastasis, and advanced clinical stages. Moreover, high EPHB2 expression predicted poor prognosis in NPC patients. EPHB2 might be a novel recurrence-related biomarker and a prognostic factor for NPC. Moreover, it might also be used as a potential treatment target for NPC.

Identification of an immune-related key gene, PPARGC1A, in the development of anaplastic thyroid carcinoma: in-silico study and in-vitro evaluation.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare malignant tumor, with short overall survival time and a high mortality rate. To date, there is a lack of effective treatment strategies for this disease. The molecular mechanisms underlying ATC have remained largely unknown. Thus, we aimed to screen the key genes that play a critical role in the genesis and development of ATC. METHODS: Datasets in the Gene Expression Omnibus database were searched and analyzed to obtain the differentially expressed genes (DEGs) between ATC and normal thyroid samples. Then, hub genes were screened out via protein-protein interaction network construction, and the key genes were filtered out from the hub genes. Afterward, the roles of the key genes were further evaluated. RESULTS: A total of 353 up-regulated and 544 down-regulated DEGs were selected, which were enriched in various pathways. Nine hub genes, including CDH1, AQP4, OCLN, SLC4A4, PAX8, DIO1, PPARGC1A, MAL2, and SLC26A4, were screened out. Then, PPARGC1A was identified as the key gene, which was positively correlated with tumor purity but negatively correlated with immune cell infiltration. Moreover, high PPARGC1A expression predicted poor prognosis in thyroid cancer. CONCLUSIONS: An immune-related gene, PPARGC1A, was filtered out as the key gene that might play critical roles in the initiation and progression of ATC. It might affect the prognosis by inhibiting immune cell infiltrations. Future experimental studies are needed to confirm the results.

Enhancement of nanoparticle-mediated double suicide gene expression driven by 'E9-hTERT promoter' switch in dedifferentiated thyroid cancer cells.

Differentiated thyroid cancer (DTC), such as papillary thyroid cancer, has a good prognosis after routine treatment. However, in the course of treatment, 5% to 20% of cases may dedifferentiate and can be transformed into dedifferentiated DTC (deDTC) or anaplastic thyroid cancer, leading to treatment failure. To date, several drugs have been used effectively for dedifferentiated thyroid cancer, whereas gene therapy may be a potential method. Literature reported that double suicide genes driven by human telomerase reverse transcriptase promoter (hTERTp) can specifically express in cancer cells and kill them. However, the weak activity of hTERTp limits its further research. To overcome this weakness, we constructed a novel chitosan nanocarrier containing double suicide genes driven by a 'gene switch' (a cascade of radiation enhancer E9 and a hTERTp). The vector was labeled with iodine-131 (131I). On one hand, E9 can significantly enhance the activity of hTERTp under the weak radiation of 131I, thereby increasing the expression of double suicide genes in deDTC cells. On the other hand, 131I also plays a certain killing role when it enters host cells. The proposed nanocarrier has good specificity for deDTC cells and thus deserves further study.

TXNIP, CXCL1, and AREG as key genes in formaldehyde-induced head and neck carcinoma: an in silico analysis.

BACKGROUND: Reports have shown that formaldehyde (FA) can induce malignant transformation in cells via complicated mechanisms. Therefore, we aimed to investigate the possible molecules, pathways, and therapeutic agents for FA-induced head and neck cancer (HNC) by using bioinformatics approaches. METHODS: High throughput data were analyzed to screen the differentially expressed genes (DEGs) between FA-treated nasal epithelium cells and controls. Then, the functions of the DEGs were annotated and the hub genes, as well as the key genes, were further screened out. Afterwards, potential drugs were predicted by using the connectivity map (CMAP) tool. RESULTS: The information of a microarray-based dataset GSE21477 was extracted and analyzed. A total of 210 upregulated and 83 downregulated DEGs were generated, which might be enriched in various pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Among these DEGs, three hub genes including TXNIP, CXCL1, and AREG, were identified as the key genes because they might affect the prognosis of HNC. Finally, a major active ingredient of blister beetles, Cantharidin, was predicted to be one of the potential drugs reversing FA-induced malignant transformation in head and neck epithelium cells. CONCLUSION: The present analysis gave us a novel insight into the mechanisms of FA-induced malignant transformation in head and neck epithelium cells, and predicted several small agents for the prevention or treatment of HNC. Future experiment studies are warranted to validate the findings.

Construction and analysis of miRNA-mRNA regulatory networks in the radioresistance of nasopharyngeal carcinoma.

Radiotherapy has been the major treatment strategy for nasopharyngeal carcinoma (NPC), while the occurrence of radioresistance may lead to cancer recurrence or progression. This study aimed to identify the key microRNAs (miRNAs) and their target genes in the development of NPC radioresistance. Public microarray data were searched and analyzed to screen the differentially expressed miRNAs (DEMs) and genes (DEGs) between radioresistant and radiosensitive NPC samples. MiRNA-mRNA networks were constructed. As a result, 5 DEMs and 195 DEGs were screened out. The DEGs were enriched in various signaling pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Several hub genes, such as IGF2, OLA1, BBS10, MMP9, and BBS7 were identified. A regulatory miRNA-mRNA network containing 87 miRNA-mRNA pairs was constructed. Then, 14 key miRNA-mRNA pairs that contained the hub genes were further filtered out. In the networks, miR-203a-3p had the largest number of target genes. Afterwards, the candidate pairs (miR-203a-3p/BTK and miR-484/OLA1) have been verified by a qRT-PCR assay. In summary, we identified several miRNAs and hub genes via big data screening. A total of 87 miRNA-mRNA pairs (including 14 key pairs) were predicted to play a crucial role in the development of NPC radioresistance. These data provide a bioinformatics basis for further exploring the molecular mechanism of radiotherapy resistance in NPC. Future studies are needed to validate the results.

[Dynamic orthosis with Shujinxi (, SJX) external granule for the treatment of collateral ligament contracture of metacarpophalangeal joint].

OBJECTIVE: To explore clinical efficacy of hand power device and Shujinxi (, SJX) external granule in treating collateral ligament contracture of metacarpophalangeal joint. METHODS: Fifty patients with collateral ligament contracture of metacarpophalangeal joint from June 2017 to January 2019 were divided into experimental and control group, 25 patients in each group. In experimental group, there were 17 males and 8 females aged from 19 to 63 years old with an average of (40.53±9.42) years old; 36 affected fingers; the courses of disease ranged from 23 to 82 days with an average of (52.37± 11.20) days; treated with hand power device and SJX external granule. In control group, there were 15 males and 10 females aged from 21 to 58 years old with an average of (42.11±8.36) years old; 32 affected fingers; the courses of diseases ranged from 18 to 71 days with an average of (48.24±12.50) days; treated with loose training of metacarpophalangeal joints. Symptoms of pain of affected finger, flexion and extension function were observed between two groups, VAS score was used to evaluate relieve degree of pain, grip size was used to evaluate recovery of grip, total active motion was applied to assess recovery of metacarpophalangeal joints, the second operation and occurrence of complications between two groups were compared. RESULTS: All patients were followed up about 8 weeks. VAS score, total active motion of metacarpophalangeal joints and grip of affected finger before and after treatment in experimental group were (4.22±1.09) point vs (1.98±1.01) point ,(17.40±6.31) ° vs (70.95±7.68) ° ,(4.83±3.09) kg vs (23.17±10.54) kg respectively, while in control group were (4.66±0.95) point vs (2.84± 1.06) point ,(16.25±5.66) ° vs (59.14±10.61) ° ,(5.06±4.05) kg vs (16.25±9.66) kg; there were statistical difference between two groups before and after treatment, and these items in experimental group after treatment were higher than that of control group (P<0.05) . There were no complicationsoccurred betweentwo groups. Onepatientinexperimentalgroup and 8 patients in controlgroupneededto bethesecondoperation, andhadsignificancedifference (P<0.05) . CONCLUSION: Handpowerdevice and SJXexternalgranulecouldobviouslyrelievesymptomsof pain of affected finger, improve recovery of grip strength, increase total active motion, and has good safety. It is an effective method for treating for the treatment of collateral ligament contracture of metacarpophalangeal joint.

Identification of a novel microRNA profile including miR-106b, miR-17, miR-20b, miR-18a and miR-93 in the metastasis of nasopharyngeal carcinoma.

BACKGROUND: Metastasis often leads to poor prognosis in nasopharyngeal carcinoma (NPC) patients. Evidence has indicated the important roles of microRNA (miRNA) in cancer metastasis. The aim of this study was to identify and verify the key miRNAs that might be involved in the development of NPC metastasis. METHODS: Microarray data were obtained and analyzed to screen the differentially expressed miRNAs (DEMs) between NPC tissues with metastasis and those without metastasis. The target genes of the DEMs were predicted and their functions were annotated. Then, candidate hub genes were screened out through protein-protein interaction analysis, and the key miRNAs were identified. Afterwards, the expression levels of the key miRNAs were assessed by qRT-PCR based on an in vitro model. RESULTS: A total of 22 DEMs were screened out, and 616 target genes were predicted. Gene Ontology (GO) and pathway enrichment analysis showed that the target genes may be enriched in a diversity of GO terms and signaling pathways. Among them, eleven hub genes were identified, such as PTEN, KAT2B, CCND1, STAT3, and MAP3K5. Moreover, a five-miRNA profile (miR-106b, miR-17, miR-20b, miR-18a and miR-93) was identified and their expression levels were tested to be up-regulated in high-metastatic NPC cells relative to low-metastatic ones. CONCLUSION: The present study revealed that five miRNAs (miR-106b, miR-17, miR-20b, miR-18a and miR-93) and several hub genes such as PTEN, KAT2B, CCND1, STAT3, and MAP3K5, might play critical roles in the development of NPC metastasis. Future investigations are needed to confirm the results.

Screening of key miRNAs and evaluation of their diagnostic and prognostic values in nasopharyngeal carcinoma.

Increasing evidence has revealed the importance of microRNA (miRNA/miR) in cancer genesis and progression. The aim of the current study was to identify the key miRNAs involved in the onset and development of nasopharyngeal carcinoma (NPC) and to further evaluate their diagnostic and prognostic values. Microarray data were obtained and analyzed to screen differentially expressed miRNAs (DEMs) between patients with NPC and healthy controls. The target genes of the DEMs were predicted and their possible functions were evaluated. The diagnostic and prognostic values of the DEMs were subsequently investigated. A total of 4 DEMs, including miR-18a, miR-135b, miR-204 and miR-497, were identified. Gene Ontology (GO) and pathway enrichment analysis revealed that the target genes were enriched in a number of GO terms and signaling pathways. The results demonstrated that the selected DEMs may present potential diagnostic factors for NPC. In addition, miR-18a [Hazard ratio (HR), 3.405; 95% confidence interval (CI), 1.334-8.693] and miR-135b (HR, 2.482; 95% CI, 1.014-6.076) may serve prognostic roles for patients with NPC. In summary, the present study identified 4 miRNAs that may be involved in the genesis and development of NPC. In addition, miR-18a and miR-135b may present useful prognostic markers for patients with NPC. Future in vitro and in vivo investigations are warranted to substantiate the results obtained in the current study.

Suppression of Type I IFN Signaling in Tumors Mediates Resistance to Anti-PD-1 Treatment That Can Be Overcome by Radiotherapy.

Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+ ) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PD-L1 (CD274) expression did not differ between the resistant and parental tumor cells. However, the expression of important molecules in the antigen presentation pathway, including MHC class I and II, as well as ß2-microglobulin, were significantly downregulated in the anti-PD-1-resistant tumors compared with parental tumors. Resistant tumors also contained fewer CD8+ (CD8α) and CD4+ tumor-infiltrating lymphocytes and reduced production of IFNγ. Localized radiotherapy induced IFNß production, thereby elevating MHC class I expression on both parental and resistant tumor cells and restoring the responsiveness of resistant tumors to anti-PD-1 therapy. Conversely, blockade of type I IFN signaling abolished the effect of radiosensitization in this setting. Collectively, these results identify a mechanism of PD-1 resistance and demonstrate that adjuvant radiotherapy can overcome resistance. These findings have immediate clinical implications for extending the efficacy of anti-PD-1 immune checkpoint therapy in patients. Cancer Res; 77(4); 839-50. ©2016 AACR.