Immunological characteristics of CD103+CD161+ T lymphocytes on chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous disease characterized by local inflammation of the upper airway and sinus mucosa. T cell-mediated immune responses play irreplaceable roles in the pathogenesis of nasal polyps. CD161+ T cells have been implicated in the pathology of several diseases through cytokine production and cytotoxic activity. However, the immunological characteristics of CD161+ T cells in nasal mucosa are still not well understood, particularly in CRSwNPs. Our research revealed a notable enrichment of CD161+ T cells in nasal tissues compared to peripheral blood, with a significantly more infiltration of CD161+ T cells in CRSwNPs compared to control nasal samples. Phenotypical analysis found that CD161+ T cells predominantly co-expressed tissue-resident memory surface markers CD103, CD69, and CD45RO. CD161+CD103+ T cells demonstrated complicated effector functions, marked by elevated levels of PD-1, CTLA-4, IL-17, and IFN-γ and diminished expression of FoxP3 and CD25. Interestingly, despite CD161+ T cells was more abundant in polyp tissues compared to normal control tissues, and then further categorizing polyp samples into distinct groups based on clinical characteristics, only the recurrent CRSwNP group showed a significant reduction in CD161+CD8+ T cells compared to the primary CRSwNP group. This finding suggested the necessity for further research to comprehensively understand the underlying mechanisms and the broader significance of CD161+ T cells in the advancement and relapse of CRSwNPs.

Tissue-resident memory T cells exhibit phenotypically and functionally heterogeneous in human physiological and pathological nasal mucosa.

Pathogens commonly enter mucosal barrier tissues and tissue-resident memory T cells (TRM) are essential for preventing mucosal lesions. However, the immunological properties of TRM cells in nasal mucosa are poorly known. In comparison with control tissues, decreasing CD103+ TRM cells were observed in Chronic rhinosinusitis with nasal polyps (CRSwNPs) and sinonasal inverted papilloma (SNIP), which presented high capability to produce effector cytokines. In CRSwNPs, we found that CD103+ TRM cells with higher cytokine and Granzyme B coexpressed high PD-1, CD103- TRM cells expressed higher IL-10. Homogenates isolated from CRSwNPs induced CD103 expression on peripheral T cells which could be inhibited by blocking TGF-ß. The frequencies of CD103+ TRM cells in CRSwNPs were extremely negatively correlated with neutrophil infiltration. CD103+ TRM cells from Staphylococcus aureus positive CRSwNPs had a stronger response to SEB. Taken together, two phenotypically and functionally distinct subsets of TRM cells exist in nasal tissues and play critical roles in the progress of CRSwNPs and SNIPs.

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

The role and potential mechanism of O-Glycosylation in gastrointestinal tumors.

Glycosylation is a critical post-translational modification (PTM) that affects the function of proteins and regulates cell signaling, thereby regulating various biological processes. Protein oxygen-N-acetylglucosamine (O-GlcNAc) glycosylation modifications are glycochemical modifications that occur within cells in the signal transduction and are frequently found in the cytoplasm and nucleus. Due to the rapid and reversible addition and removal, O-GlcNAc modifications are able to reversibly compete with certain phosphorylation modifications, immediately regulate the activity of proteins, and participate in kinds of cellular metabolic and signal transduction pathways, playing a pivotal role in the regulation of tumors, diabetes, and other diseases. This article provided a brief overview of O-GlcNAc glycosylation modification, introduced its role in altering the progression and immune response regulation of gastrointestinal tumors, and discussed its potential use as a marker of tumor neogenesis.

Effects of N6-Methyladenosine Modification on Cancer Progression: Molecular Mechanisms and Cancer Therapy.

N6-methyladenosine (m6A) is a major internal epigenetic modification in eukaryotic mRNA, which is dynamic and reversible. m6A is regulated by methylases ("writers") and demethylases ("erasers") and is recognized and processed by m6A-binding proteins ("readers"), which further regulate RNA transport, localization, translation, and degradation. It plays a role in promoting or suppressing tumors and has the potential to become a therapeutic target for malignant tumors. In this review, we focus on the mutual regulation of m6A and coding and non-coding RNAs and introduce the molecular mechanism of m6A methylation involved in regulation and its role in cancer treatment by taking common female malignant tumors as an example.

Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: The role of surgery compared with reirradiation in the primary treatment of patients with resectable, locally recurrent nasopharyngeal carcinoma (NPC) who have previously received radiotherapy is a matter of debate. In this trial, we compared the efficacy and safety outcomes of salvage endoscopic surgery versus intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent NPC. METHODS: This multicentre, open-label, randomised, controlled, phase 3 trial was done in three hospitals in southern China. We included patients aged 18-70 years with a Karnofsky Performance Status score of at least 70 who were histopathologically diagnosed with undifferentiated or differentiated, non-keratinising, locally recurrent NPC with tumours confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Eligible patients were randomly assigned (1:1) to receive either endoscopic nasopharyngectomy (ENPG group) or IMRT (IMRT group). Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre. Treatment group assignment was not masked. The primary endpoint was overall survival, compared between the groups at 3 years. Efficacy analyses were done by intention to treat. Safety analysis was done in patients who received treatment according to the treatment they actually received. This trial was prospectively registered at the Chinese Clinical Trial Registry, ChiCTR-TRC-11001573, and is currently in follow-up. FINDINGS: Between Sept 30, 2011, and Jan 16, 2017, 200 eligible patients were randomly assigned to receive either ENPG (n=100) or IMRT (n=100). At a median follow-up of 56·0 months (IQR 42·0-69·0), 74 patients had died (29 [29%] of 100 patients in the ENPG group and 45 [45%] of 100 patients in the IMRT group). The 3-year overall survival was 85·8% (95% CI 78·9-92·7) in the ENPG group and 68·0% (58·6-77·4) in the IMRT group (hazard ratio 0·47, 95% CI 0·29-0·76; p=0·0015). The most common grade 3 or worse radiation-related late adverse event was pharyngeal mucositis (in five [5%] of 99 patients who underwent ENPG and 26 [26%] of 101 patients who underwent IMRT). Five [5%] of the 99 patients who underwent ENPG and 20 [20%] of the 101 patients who underwent IMRT died due to late toxic effects specific to radiotherapy; attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity. INTERPRETATION: Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent NPC. These results suggest that ENPG could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy. FUNDING: Sun Yat-sen University Clinical Research 5010 Program.

Clinical efficacy and safety of cervical intralymphatic immunotherapy for house dust mite allergic rhinitis: A pilot study.

BACKGROUND: Previous studies have demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, because of the private location of inguinal lymph nodes, inguinal ILIT is relatively inconvenient. We proposed a novel form of ILIT that involves 3 injections of allergen into cervical lymph nodes. The aim of this study is to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced allergic rhinitis (AR) in adults. METHODS: In this study, we performed a prospective cohort study to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced AR in adults, by comparing the symptom scores, quality-of-life scores (QOLS) and drug scores (use of rescue medication) before and after treatment. Meanwhile, side events were also recorded. RESULTS: Cervical ILIT elicited no moderate-severe adverse events. Patients receiving cervical ILIT experienced a significant improvement in nasal symptoms, eye symptoms and quality of life, as compared to baseline (P all <0.001). A reduction in the use of rescue medication was also demonstrated (P < 0.001). CONCLUSIONS: In this first-in-human clinical study, cervical ILIT was demonstrated safe and induced allergen tolerance after 3 injections.