Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer.

BACKGROUND: Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery. METHODS: A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study. RESULTS: Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful. CONCLUSION: JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.

Combining radiomics with thyroid imaging reporting and data system to predict lateral cervical lymph node metastases in medullary thyroid cancer.

BACKGROUND: Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide surgical decisions and ensure that patients receive the most appropriate and effective surgery. To our knowledge, no studies have been published that use radiomics analysis to forecast LCLNM in MTC patients. The purpose of this study is to develop a radiomics combined with thyroid imaging reporting and data system (TI-RADS) model that can use preoperative thyroid ultrasound images to noninvasively predict the LCLNM status of MTC. METHODS: We retrospectively included 218 MTC patients who were confirmed from postoperative pathology as LCLNM negative (n=111) and positive (n=107). Ultrasound features were selected using the Student's t-test, while radiomics features are first extracted from preoperative thyroid ultrasound images, and then a two-step feature selection approach was used to select features. These features are then used to establish three regularized logistic regression models, namely the TI-RADS model (TM), the radiomics model (RM), and the radiomics-TI-RADS model (RTM), in 5-fold cross-validation to determine the likelihood of the LCLNM. The Delong's test and decision curve analysis (DCA) were used to evaluate and compare the performance of the models. RESULTS: The ultrasound features of margin and TI-RADS level, and a total of 12 selected radiomics features, were significantly different between the LCLNM negative and positive groups (p<0.05). The TM, RM, and RTM yielded an averaged AUC of 0.68±0.05, 0.78±0.06, and 0.82±0.05 in the 5-fold cross-validation dataset, respectively. RM and RTM are statistically better than TM (p<0.05 and p<0.001) according to Delong test. DCA demonstrates that RTM brings more benefit than TM and RM. CONCLUSIONS: We have developed a joint radiomics-based model for noninvasive prediction of the LCLNM in MTC patients solely using preoperative thyroid ultrasound imaging. It has the potential to be used as a complementary tool to help guide treatment decisions for this rare form of thyroid cancer.

Aspirin and Celecoxib Regulate Notch1/Hes1 Pathway to Prevent Pressure Overload-Induced Myocardial Hypertrophy.

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1ß) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

The critical role of IFNγ in the epidermotropic migration of lymphocytes in oral lichen planus.

INTRODUCTION: The chemokines play a crucial role in the recruitment of lymphocytes in oral lichen planus, and the activated epithelial cells are the main producers of the chemokines. However, the signals provoking chemokine secretion still remain to be elucidated. METHODS: The global expression profile of chemokines in oral epithelial cell line induced by IFNγ was determined by microarray analysis. The gene and protein expression was validated in primary culture of oral epithelial cells, and the effects of IFNγ on regulating chemokine production were compared with that of TNFα and IL2. Moreover, the capability of primary culture of oral epithelial cells to attract peripheral lymphocytes in response to IFNγ was investigated in oral lichen planus patients, and the cell phenotype of the recruited lymphocytes was analyzed using flow cytometry. RESULTS: IFNγ triggered the expression of multiple chemokines in the oral epithelial cells. The expression pattern of the chemokines closely resembled that in the epithelial cell layer of oral lichen planus lesions. Compared with IL2 and TNFα, IFNγ demonstrated a distinct maximal effect on the chemokines secretion in primary culture of oral epithelial cells. The migration of peripheral lymphocytes toward the culture supernatant of IFNγ-treated primary culture of oral epithelial cells was significantly enhanced in the oral lichen planus group compared to that in the healthy control group. CONCLUSION: IFNγ plays an important role in the chemokine secretion and epidermotropic migration of lymphocytes in oral lichen planus.

An Adaptive Parameterized Domain Mapping Method and Its Application in Wheel-Rail Coupled Fault Diagnosis for Rail Vehicles.

The rapid development of cities in recent years has increased the operational pressure of rail vehicles, and due to the characteristics of rail vehicles, including harsh operating environment, frequent starting and braking, resulting in rails and wheels being prone to rail corrugation, polygons, flat scars and other faults. These faults are coupled in actual operation, leading to the deterioration of the wheel-rail contact relationship and causing harm to driving safety. Hence, the accurate detection of wheel-rail coupled faults will improve the safety of rail vehicles' operation. The dynamic modeling of rail vehicles is carried out to establish the character models of wheel-rail faults including rail corrugation, polygonization and flat scars to explore the coupling relationship and characteristics under variable speed conditions and to obtain the vertical acceleration of the axle box. An APDM time-frequency analysis method is proposed in this paper based on the PDMF adopting Rényi entropy as the evaluation index and employing a WOA to optimize the parameter set. The number of iterations of the WOA adopted in this paper is decreased by 26% and 23%, respectively, compared with PSO and SSA, which means that the WOA performs at faster convergence speed and with a more accurate Rényi entropy value. Additionally, TFR obtained using APDM realizes the localization and extraction of the coupled fault characteristics under rail vehicles' variable speed working conditions with higher energy concentration and stronger noise resistance corresponding to prominent ability of fault diagnosis. Finally, the effectiveness of the proposed method is verified using simulation and experimental results that prove the engineering application value of the proposed method.

Application of single-cell RNA sequencing in head and neck squamous cell carcinoma.

Single-cell RNA sequencing has been broadly applied to head and neck squamous cell carcinoma (HNSCC) for characterizing the heterogeneity and genomic mutations of HNSCC benefiting from the advantage of single-cell resolution. We summarized most of the current studies and aimed to explore their research methods and ideas, as well as how to transform them into clinical applications. Through single-cell RNA sequencing, we found the differences in tumor cells' expression programs and differentiation tracks. The studies of immune microenvironment allowed us to distinguish immune cell subpopulations, the extensive expression of immune checkpoints, and the complex crosstalk network between immune cells and non-immune cells. For cancer-associated fibroblasts (CAFs), single-cell RNA sequencing had made an irreplaceable contribution to the exploration of their differentiation status, specific CAFs markers, and the interaction with tumor cells and immune cells. In addition, we demonstrated in detail how single-cell RNA sequencing explored the HNSCC epithelial-to-mesenchymal transition (EMT) model and the mechanism of drug resistance, as well as its clinical value.

Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer.

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Lastly, MAGEB2 is significantly associated with immune cell infiltration (CD8+ T cells particularly, IHC staining confirmed that as the protein expression of MAGEB2 increased, the protein level of CD8 (representing tumor-infiltrating CD8 + T cells) decreased in vitro), immunomodulators (knockdown or overexpression of MAGEB2 on LC cell lines can significantly affect the chemokine/cytokine secretion in vitro), and immunogenicity(TMB) in LC, which hints that MAGEB2 is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for LC patients.

The emerging role of transcription factor FOXP3 in thyroid cancer.

Transcription factor FOXP3 is a crucial regulator in the development and function of regulatory T cells (Treg) that are essential for immunological tolerance and homeostasis. Numerous studies have indicated the correlation of tumor infiltrating FOXP3+ Treg upregulation with poor prognostic parameters in thyroid cancer, including lymph node metastases, extrathyroidal extension, and multifocality. Most immune-checkpoint molecules are expressed in Treg. The blockage of such signals with checkpoint inhibitors has been approved for several solid tumors, but not yet for thyroid cancer. Thyroid abnormalities may be induced by checkpoint inhibitors. For example, hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm are more frequently associated with anti-PD-1 antibodies (pembrolizumab and nivolumab). Therefore, Targeting FOXP3+ Treg may have impacts on checkpoint molecules and the growth of thyroid cancer. Several factors may impact the role and stability of FOXP3, such as alternative RNA splicing, mutations, and post-translational modification. In addition, the role of FOXP3+ Treg in the tumor microenvironment is also affected by the complex regulatory network formed by FOXP3 and its transcriptional partners. Here we discussed how the expression and function of FOXP3 were regulated and how FOXP3 interacted with its targets in Treg, aiming to help the development of FOXP3 as a potential therapeutic target for thyroid cancer.

Mechanism of Astrin in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma(HNSCC) is a malignant epidermal tumor that seriously threatens human life and health. The main factors affecting the death of patients are local recurrence and lymph node metastasis. Astrin antibody is the basic component of the mitotic spindle required for normal chromosome separation and later development. There are few domestic studies on the mechanism of Astrin in HNSCC. Based on this, this article is studying Astrin in HNSCC. The expression and function of Astrin, and analyze its correlation with clinical pathological parameters and prognosis of patients, and further explore the relevant mechanisms involved in the progression of Astrin in HNSCC. In this experiment, the real-time fluorescent quantitative polymerase chain reaction (PCR) method was used to detect the expression of the Astrin antibody in HNSCC cell lines A and B. Secondly, this article will focus on high metastatic HNSCC cells B. Divided into five groups (blank control group, overexpression positive group, overexpression negative control group, expression suppression positive group, expression suppression negative control group), using real-time fluorescent quantitative PCR technology to detect the expression of Astrin in each group, and then speculate the mechanism of Astrin in HNSCC. Experiments have shown that Astrin is expressed in A and B cells, but its expression in B is significantly higher than its expression in A, and the difference is statistically significant (P<0.001). This shows that the inhibition of Astrin expression has a significant anti-tumor effect and that Astrin plays an important role in the occurrence and development of tumors. It is expected to provide new ideas and reference basis for exploring new therapeutic strategies for targeted therapy of HNSCC.

Necessity of Intraoperative Level IIA Lymph Node Dissection in Patients with Carotid Body Tumors: A Retrospective Study of 126 Cases.

BACKGROUND: Carotid body tumors (CBTs) are relatively uncommon neoplasms that rarely have malignant potential. However, malignant CBTs (MCBTs) are still associated with a poor prognosis and the treatment is still challenging clinically. Therefore, we evaluated the necessity of intraoperative level IIA lymph node dissection in patients with CBT. METHODS: The clinical characteristics, intraoperative details, and pathological diagnosis of 126 CBT patients who had undergone surgery were retrospectively reviewed. The patients were divided into 2 groups according to whether level IIA lymph node dissection was performed. The prognosis was analyzed using Kaplan-Meier curves and Cox model multivariate survival analysis. RESULTS: Among the 126 patients, 7 patients (10.3%) in the selective lymph node dissection (SLND) group (68 patients) were diagnosed with MCBTs with evidence of lymph node metastasis. Two patients (3.4%) in the lymph node nondissection (LNND) group (58 patients) were diagnosed with MCBTs later after the second operation because they could not be diagnosed as malignant initially because of the lack of lymph node pathology results although the pathology of the primary lesion showed features of malignancy. The SLND group had a significantly higher relapse-free survival rate than the LNND group (94.1% vs. 79.3%, p = 0.021). Patients with a confirmed diagnosis had a better prognosis than those with insufficient evidence of a malignancy due to the lack of lymph node information. Twenty-nine patients in the SLND group and 26 patients in the LNND group had postoperative nerve injuries, with no significant difference between the groups (p = 0.879). CONCLUSION: Intraoperative dissection of level IIA lymph nodes around the tumor in CBT patients can help improve the diagnosis and prognosis of MCBTs without causing additional cranial nerve injury.

Microfluidic synthesis of pyrrolidin-2-ones via photoinduced organocatalyzed cyclization of styrene, α-bromoalkyl esters and primary amines.

A green and efficient reaction route for the synthesis of pyrrolidin-2-ones via photoinduced organocatalyzed three-component cyclization of styrene, tertiary α-bromoalkyl esters and primary amines in a microchannel reactor under visible light conditions has been developed. Moreover, the overall process can be carried out under mild conditions without using a metal. In addition, a reasonable reaction mechanism was proposed based on control experiments.

Clinical characteristics and risk factors of major oral ulcers in the mandibular retromolar region in children.

OBJECTIVES: To describe the characteristics of major aphthous ulcers (MjOU) in children and analyze its potential risk factors. MATERIALS AND METHODS: Data were collected from the National Clinical Research Center for Oral Diseases of China between 2012 and 2017. Children younger than 15 years old, who had a giant mucosa ulcer (≥ 1 cm in diameter) and met the diagnostic criteria for MjOU were included in this study. Differences were compared between two subgroups of patients based on the location of the ulcerous lesions. A measurement of ratio (TBR) between the length of the mandibular second molar tooth germ and the height of the mandible was performed in children with MjOU lesions located in the mandibular retromolar pad region (MjOU-P) and their age- and sex-matched controls. RESULTS: A total of 1067 children were diagnosed with oral ulcers during the study period, of which 125 (11.7%, 95% CI: 9.8%-13.7%) met the diagnostic criteria for MjOU. More than half (n = 64, 51.2%) of the MjOU cases were MjOU-P, which had a male predilection (n = 52, 81.3%) with a significant majority at 7 to 9 years of age (n = 43, 67.2%). In comparison to the MjOU located in other regions, MjOU-P lasted longer in duration and had more comorbidities. Logistic regression analysis showed that MjOU-P was statistically significantly associated with TBR controlling age and gender. CONCLUSIONS: MjOU-P is a predominant form of MjOU in children and is a distinct subgroup of major ulcers that is likely associated with the development of the mandibular second molars. CLINICAL RELEVANCE: This study is the first to describe the demographic and clinical features of MjOU in children, which may facilitate the identification and treatment of these patients.

Extraskeletal Ewing sarcoma of thyroid gland: A case report. / ç”²çŠ¶è ºéª¨å¤–å°¤å› è‚‰ç˜¤1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Extraskeletal Ewing sarcoma is a rare event, and extraskeletal Ewing sarcoma of the thyroid gland is even rarer. It has non-specific clinical manifestation and difficulty in early diagnosis. The diagnosis mainly depends on histology and immunohistochemistry. It possesses the features of high malignancy, high rate of local recurrence, and distant metastasis. Currently, the aggressive multimodal treatment contains surgery, chemotherapy, and radiotherapy. This study presented a case of extraskeletal Ewing sarcoma arising in the thyroid gland of a 30-year-old woman, who presented with supraclavicular mass and sense of dysphagia obstruction in Department of Otolaryngology, Head and Neck Surgery, Second Xiangya Hospital, Central South University in 2018. Imaging studies demonstrated a cystic-solid mass in inferior of the left leaf of thyroid gland and in the posterior of the trachea and esophagus. The patient underwent localized tumor resection. The pathological diagnosis revealed that it was a small round cell tumor, and the immunohistochemistry results were considered to be extraskeletal Ewing sarcoma. Subsequently, the patient was given chemotherapy and local radiation therapy. There was no evidence of tumor recurrence or metastasis.

H255Y and K508R missense mutations in tumour suppressor folliculin (FLCN) promote kidney cell proliferation.

Germline H255Y and K508R missense mutations in the folliculin (FLCN) gene have been identified in patients with bilateral multifocal (BMF) kidney tumours and clinical manifestations of Birt-Hogg-Dubé (BHD) syndrome, or with BMF kidney tumours as the only manifestation; however, their impact on FLCN function remains to be determined. In order to determine if FLCN H255Y and K508R missense mutations promote aberrant kidney cell proliferation leading to pathogenicity, we generated mouse models expressing these mutants using BAC recombineering technology and investigated their ability to rescue the multi-cystic phenotype of Flcn-deficient mouse kidneys. Flcn H255Y mutant transgene expression in kidney-targeted Flcn knockout mice did not rescue the multi-cystic kidney phenotype. However, expression of the Flcn K508R mutant transgene partially, but not completely, abrogated the phenotype. Notably, expression of the Flcn K508R mutant transgene in heterozygous Flcn knockout mice resulted in development of multi-cystic kidneys and cardiac hypertrophy in some mice. These results demonstrate that both FLCN H255Y and K508R missense mutations promote aberrant kidney cell proliferation, but to different degrees. Based on the phenotypes of our preclinical models, the FLCN H255Y mutant protein has lost it tumour suppressive function leading to the clinical manifestations of BHD, whereas the FLCN K508R mutant protein may have a dominant negative effect on the function of wild-type FLCN in regulating kidney cell proliferation and, therefore, act as an oncoprotein. These findings may provide mechanistic insight into the role of FLCN in regulating kidney cell proliferation and facilitate the development of novel therapeutics for FLCN-deficient kidney cancer.

Visualisation of the vomerovaginal canal during endonasal transpterygoid approaches and CT imaging diagnosis.

The vomerovaginal canal (VVC) and palatovaginal canal (PVC) are two canals that open forward to the posterior wall of the pterygopalatine fossa (PPF). Although the anatomy and computed tomography (CT) appearances of the PVC have been well studied, the VVC has been rarely reported, especially in endoscopic examinations. Some studies have even failed to distinguish the PVC from the VVC on CT images. The purpose of this study was to demonstrate the anatomy of the VVC on endoscopy and reveal its differences from the PVC, and to analyse the relative positions of the VVC, PVC, and pterygoid canal on CT images. Ten dry skull bases were studied to observe the structures involved in the formation of the VVC. Dissection of four cadaveric heads was performed to demonstrate the anatomy of the VVC on endoscopy. Coronal CT image analysis in 70 patients was conducted to evaluate the distances and relative positions between the VVC, PVC, and pterygoid canal. The PVC and VVC were also compared on axial CT images. The osteological study showed the top wall of the VVC was the antero-inferior wall of the sphenoid sinus. The VVC may be a helpful landmark in endoscopic endonasal transpterygoid approaches. Steps and discrimination in the dissections of the VVC and PVC were described. The interval between the PVC and VVC could be observed on both coronal and axial CT images. The coronal CT images of patients showed differences in the positions and distances among the three canals at both the anterior and posterior apertures of the PVC. The VVC can be easily mistaken for the PVC if its existence is not suspected. The anatomical morphologies and trajectories of the VVC and PVC differed on both nasal endoscopy and CT. The existence of the VVC should be considered during surgery and CT diagnosis within this area.

Alteration of salivary glycopatterns in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is one of the most common oral mucosal lesions affecting 0.5-2% of the adult population. It is difficult to distinguish between OLP and other oral mucosal diseases. Structural changes in the glycans of saliva proteins might be reliable indicators of OLP. However, little is known about the alteration of salivary glycopatterns during OLP. OBJECTIVE: We aimed to investigate the alterations of salivary protein glycosylation related to OLP. MATERIAL AND METHODS: Twenty-eight patients with OLP and 30 age- and sex-matched healthy volunteers (HVs) were enrolled in the test group to probe the difference of salivary glycopatterns using lectin microarrays. The lectin blotting were further utilized to validate the expression of certain glycans. RESULTS: The glycoproteins recognized by three lectins [Aleuria aurantia lectin (AAL); Phytolacca americana (PWM); Phaseolus vulgaris agglutinin (E + L), (PHA-E + L)] were mainly increasing in the saliva of OLP. Meanwhile, these glycoproteins also exhibited significant age-associated alterations. CONCLUSIONS: This study provided a new basic insight into salivary glycopatterns in OLP and helped to develop new potential biomarkers for diagnosis of OLP.

TLR4-induced B7-H1 on keratinocytes negatively regulates CD4+ T cells and CD8+ T cells responses in oral lichen planus.

Oral lichen planus (OLP) is a T-cell-mediated autoimmune mucocutaneous disease affected by the interactions among the keratinocytes, CD4+ T cells and CD8+ T cells. B7-H1 induced by Toll-like receptors (TLRs) can suppress T-cell immune reaction, thereby resulting in immune tolerance. However, the role of TLR-mediated B7-H1 on keratinocytes in the immune response of OLP is still unknown. The present study showed that TLR4 could induce time-coursed B7-H1 expression on oral keratinocytes, and blocking NF-κB or PI3K/mTOR pathway downregulated B7-H1 transcriptional expression. Moreover, TLR4-stimulated oral keratinocytes inhibited the proliferation of OLP CD4+ T cells and OLP CD8+ T cells, and simultaneously prompted their apoptosis. Blockade of keratinocyte-associated B7-H1 restored the declined proliferation of OLP CD4+ T cells and OLP CD8+ T cells, and prevented their increased apoptosis. Therefore, TLR4-upregulated B7-H1 on keratinocytes could decelerate immune responses of CD4+ T cells and CD8+ T cells in OLP.

Declined hTERT expression of peripheral blood CD4(+) T cells in oral lichen planus correlated with clinical parameter.

BACKGROUND: Oral lichen planus (OLP) is a chronic, T-cell-mediated inflammatory autoimmune disease. Human telomerase reverse transcriptase (hTERT), a catalytic subunit bearing the enzymatic activity of telomerase, may have a unique function in regulating the activation, proliferation, and function of T lymphocytes. The goal of this study was to investigate the expression of hTERT in CD4(+) and CD8(+) T cells from patients with OLP and its correlation with clinical parameter. METHODS: The disease severity of OLP was assessed by RAE (reticular, atrophic, erosive) scoring system. Expressions of hTERT in CD4(+) T cells and CD8(+) T cells isolated from peripheral blood of patients with OLP were detected by real-time PCR, and their correlations with clinical features were analyzed. RESULTS: hTERT mRNA levels in CD4(+) T cells of OLP were significantly lower than that of controls, while the levels in CD8(+) T cells showed no statistical difference. The expression of hTERT in CD4(+) T cells and CD8(+) T cells was neither associated with disease severity nor gender. CD4(+) T cells of OLP patients with the age ≤50 had markedly decreased hTERT levels compared with controls, but CD8(+) T cells did not. CONCLUSIONS: A divergent hTERT pattern between CD4(+) and CD8(+) T cells was implicated in OLP. Decreased hTERT in CD4(+) T cells might be responsible for the immune dysfunction in OLP.

The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma.

In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.

Comprehensive investigation into the influence of glycosylation on head and neck squamous cell carcinoma and development of a prognostic model for risk assessment and anticipating immunotherapy.

Background: It has been well established that glycosylation plays a pivotal role in initiation, progression, and therapy resistance of several cancers. However, the correlations between glycosylation and head and neck squamous cell carcinoma (HNSCC) have not been elucidated in detail. Methods: The paramount genes governing glycosylation were discerned via the utilization of the Protein-Protein Interaction (PPI) network and correlation analysis, coupled with single-cell RNA sequencing (scRNA-seq) analysis. To construct risk models exhibiting heightened predictive efficacy, cox- and lasso-regression methodologies were employed, and the veracity of these models was substantiated across both internal and external datasets. Subsequently, an exploration into the distinctions within the tumor microenvironment (TME), immunotherapy responses, and enriched pathways among disparate risk cohorts ensued. Ultimately, cell experiments were conducted to validate the consequential impact of SMS in Head and Neck Squamous Cell Carcinoma (HNSCC). Results: A total of 184 genes orchestrating glycosylation were delineated for subsequent scrutiny. Employing cox- and lasso-regression methodologies, we fashioned a 3-gene signature, proficient in prognosticating the outcomes for patients afflicted with HNSCC. Noteworthy observations encompassed distinctions in the Tumor Microenvironment (TME), levels of immune cell infiltration, and the presence of immune checkpoint markers among divergent risk cohorts, holding potentially consequential implications for the clinical management of HNSCC patients. Conclusion: The prognosis of HNSCC can be proficiently anticipated through risk signatures based on Glycosylation-related genes (GRGs). A thorough delineation of the GRGs signature in HNSCC holds the potential to facilitate the interpretation of HNSCC's responsiveness to immunotherapy and provide innovative strategies for cancer treatment.