CRISPR/Cas9 technology is a powerful genome manipulation tool in insects. However, little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants. This study generated homozygous mutants of the insulin receptor gene 2 (NlInR2) in the brown planthopper (Nilaparvata lugens) using CRISPR/Cas9 genome editing. Both frameshift mutants, E5_D17 and E6_I7, differentiated towards long wings, but there were differences in wing morphology, with E5_D17 showing wing deformities. Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants, as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17. Additionally, the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein. RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%, suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions. Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.

Laryngeal cancer (LC) is the second most common head and neck cancer and has a decreasing 5-year survival rate worldwide. Circular RNAs (circRNAs) regulate cancer development in diverse ways based on their distinct biogenesis mechanisms and expansive regulatory roles. However, currently, there is little research on how exosomal circRNAs are involved in the development of LC. Here, we demonstrated that circPVT1, a circRNA derived from the well-studied long noncoding RNA PVT1, is correlated with disease progression in LC and promotes angiogenesis both in vivo and in vitro. Mechanistically, circPVT1 is loaded into LC cell-secreted exosomes and taken up by vascular epithelium cells. By sponging miR-30c-5p, exosomal circPVT1 promotes Rap1b expression, which dramatically enhances vascular endothelial growth factor receptor 2 and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation, ultimately resulting in the induction of angiogenesis. Furthermore, our xenograft models demonstrated that the combination of short hairpin RNA-circPVT1 and cetuximab showed high efficacy in inhibiting tumor growth and angiogenesis. Collectively, these findings uncover a novel mechanism of exosomal circRNA-mediated angiogenesis modulation and provide a preclinical rationale for testing this analogous combination in patients with LC.

Dexmedetomidine (DEX) has been described as a safe sedative in clinical practice, but its effects on the pathophysiological traits of obstructive sleep apnea (OSA) are unclear. We estimated the effects of DEX sedation on the four key pathophysiological traits of OSA (pharyngeal collapsibility, dilator muscle function, arousal threshold, and loop gain) in adult patients with OSA by conducting a secondary analysis of a prospective diagnostic trial. Pathophysiological traits estimated from polysomnography and the respiratory parameters under natural sleep and DEX-induced sleep were compared. Bivariate and multivariate linear regression analyses were used to estimate the relationship between pathophysiological traits and OSA severity for both sleep states. Adult patients with OSA had a significantly higher pharyngeal collapsibility (Vpassive : 44.9 [15.7 to 53.8] vs. 53.3 [34.2 to 66.3] %eupnea , p < 0.001), arousal threshold (178.5 [132.5 to 234.6] vs. 140.5 [123.2 to 192.3] %eupnea , p < 0.001), and loop gain (LG1: 0.74 ± 0.25 vs. 0.60 ± 0.17, p < 0.001; LGn: 0.52 ± 0.12 vs. 0.44 ± 0.08, p < 0.001) during DEX-induced sleep compared with natural sleep. There was no significant difference in dilator muscle function or PSG respiratory parameters between natural versus DEX-induced sleep states. Bivariate regression analysis showed varying degrees of correlation between OSA traits and severity. Multiple regression analysis indicated that collapsibility was the strongest predictor of the apnea-hypopnea index for both sleep states. Dexmedetomidine sedation in patients with OSA increased the pharyngeal collapsibility without impairing dilator muscle function, while elevating arousal threshold and increasing loop gain.

Survival rates for children and adolescents diagnosed with malignancy have been steadily increasing due to advances in oncology treatments. These treatments can have a toxic effect on the gonads. Currently, oocyte and sperm cryopreservation are recognized as well-established and successful strategies for fertility preservation for pubertal patients, while the use of gonadotropin-releasing hormone agonists for ovarian protection is controversial. For prepubertal girls, ovarian tissue cryopreservation is the sole option. However, the endocrinological and reproductive outcomes after ovarian tissue transplantation are highly heterogeneous. On the other hand, immature testicular tissue cryopreservation remains the only alternative for prepubertal boys, yet it is still experimental. Although there are several published guidelines for navigating fertility preservation for pediatric and adolescent patients as well as transgender populations, it is still restricted in clinical practice. This review aims to discuss the indications and clinical outcomes of fertility preservation. We also discuss the probably effective and efficient workflow to facilitate fertility preservation.

患儿 男，7岁2月龄，因“生长停滞伴体重增长明显1年余”就诊，有典型的非促肾上腺皮质激素依赖性皮质醇增多症的临床表现及实验室检查特点，小剂量-大剂量地塞米松序贯试验提示反常性尿质醇增高。经肾上腺影像学检查及组织病理结果诊断为原发性色素结节性肾上腺皮质病，肾上腺组织基因检测发现PRKACA基因拷贝数重复变异，但在患儿和父母外周血中没有发现该基因变异。

BACKGROUND:Humans are exposed to various chemicals, including organophosphate esters (OPEs), phthalates (PAEs), and phenols. The effects on early reproductive outcomes of in vitro fertilization (IVF) remain unclear. METHODS:We recruited 192 women and 157 men who underwent IVF treatment. A total of forty-nine urinary chemicals were detected, including six OPEs, fifteen PAEs, six parabens, two chlorophenols, nine bisphenols, five benzophenones, and six synthetic phenolic antioxidants. We examined the individual and joint effects of parental chemical exposure on early reproductive outcomes. RESULTS:We found that certain chemicals were associated with early reproductive outcomes in Poisson regression models. For example, urinary diphenyl phosphate was negatively associated with high-quality embryos in both female (β: -0.12, 95%CI: -0.17, -0.07) and male partners (β: -0.09, 95%CI: -0.15, -0.03). A negative association was found between mixed chemicals and high-quality embryos in Bayesian kernel machine regression, weighted quantile sum regression (β: -0.34, 95%CI: -0.60, -0.07), and quantile-based g-computation model (β: -0.69, 95%CI: -1.34, -0.05) among female partners. Paternal mixture exposure was not associated with early reproductive outcomes. CONCLUSIONS:Our results indicated that increased exposure to environmental chemicals was associated with adverse early reproductive outcomes of IVF, especially female partners.

Fertilization is a complex and highly regulated process that involves a series of molecular interactions between sperm and oocytes. However, the mechanisms of proteins involved in human fertilization, such as that of testis-specific SPACA4, remain poorly understood. Here we demonstrated that SPACA4 is a spermatogenic cell-specific protein. SPACA4 is expressed during spermatogenesis, upregulated in early-stage spermatids, and downregulated in elongating spermatids. SPACA4 is an intracellular protein that locates in the acrosome and is lost during the acrosome reaction. Incubation with antibodies against SPACA4 inhibited the binding of spermatozoa to zona pellucida. SPACA4 protein expression levels across different semen parameters were similar but varied significantly among patients. A prospective clinical study found no association between SPACA4 protein levels and fertilization or cleavage rates. Thus, the study suggests a novel function for SPACA4 in human fertilization in a non-dose-dependent manner. However, a larger clinical trial is required to evaluate the potential use of sperm SPACA4 protein levels to predict fertilization potential.

This study assessed the difference in singleton live birth rate (SLBR) between preimplantation genetic testing for aneuploidy (PGT-A) and non-PGT in patients undergoing elective single frozen blastocyst transfer (eSFBT). This retrospective cohort study evaluated 10,701 cycles of eSFBT, including PGT-A (n = 3125) and non-PGT (n = 7576). Cycles were further stratified according to age at retrieval. The main outcome was SLBR; secondary outcomes were clinical pregnancy, conception rates, and multiple live birth rate. Confounders were adjusted using multivariable logistic regression models, and the trend test was performed using the general linear model. SLBR was negatively correlated with age in the non-PGT group (p-trend < 0.001) but not in PGT-A group (p-trend = 0.974). Stratified by the age, SLBR were significantly different between two groups except for the 20–24-year-old group: PGT-A vs non-PGT group in 20–24, 25–29, 30–34, 35–39 and ≥ 40-year-old subgroups were, 53.5

In order to precisely select MIBC patients (pts) for bladder preservation, it's necessary to establish strict standard for cCR. Our study was conducted to evaluate the efficacy of tislelizumab combined with gemcitabine and cisplatin (GC) as a bladder-sparing therapy for utDNA-defined cCR pts. The study enrolled pts were cisplatin-eligible with no carcinoma in situ. Firstly, pts received maximal TURBT, then received tislelizumab 200 mg in day 1 (D1), cisplatin 70 mg/m2 D2, and gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks for 4 cycles. Secondly, pts further received utDNA testing and clinical restaging were performed. Pts who were utDNA-defined cCR (defined as negative for utDNA, normal urine cytology and MRI imaging, plus bladder biopsies≤cTa.) proceeded bladder preservation, while non-utDNA-defined cCR pts underwent radical cystectomy (RC). Finally, all pts received tislelizumab every 3 weeks for 8 cycles followed by surveillance. The primary endpoint was utDNA-defined cCR rate. Secondary endpoints were 1-year bladder intact disease-free survival(BIDFS) rate, OS and safety. 16 MIBC pts enrolled between Jul. 2021 and Sep. 2022 and 14 pts were analyzed (male 85.7%; median age 62(39-75)). cT2=21.4%, cT3=64.3%, cT4a=14.3%, cN0=78.6%, cN1=21.4%. 100% pts received maximal TURBT. The median number of tislelizumab and GC cycles were 4 (4-4) and 4 (3-4), respectively. Median follow up was 13.2 months (7.9-17.1). The utDNA-defined cCR rate was 35.7% (95% CI, 10.7%-60.7%). Non-utDNA-defined cCR pts received RC and all were≥pT1N0M0. The 1-year BIDFS rate and 1-year OS rate for utDNA-defined cCR pts were 100% (95%CI, 100%-100%) and 100% (95%CI, 100%-100%), respectively. Grade 1-2 immune related adverse events, including rash (n=4), ALT/AST increased (n=3), hyperthyroidism (n=1) and hyperglycaemia (n=1). The interim results demonstrated the utDNA-defined cCR can successfully select MIBC pts for precise bladder-sparing treatment.

PurposeThe aim of this study was to retrospectively evaluate the oncologic outcomes of sinonasal malignancies (SNMs) of various histologic subtypes and investigate the impact of multimodality treatment on prognosis of SNM.MethodsSNM patients treated with curative-intent surgery from 2000 to 2018 were included. The primary outcomes were overall survival (OS). Survival was then assessed through Cox proportional hazards models.ResultsThree hundred and three patients were eligible for the analysis. The 5-year OS and event-free survival (EFS) were 61.0% (95% CI: 55.4%–67.1%) and 46.2% (95% CI: 40.4%–52.7%). The 5-year OS was the worst for malignant melanoma and the best for adenocarcinoma. Patients who received surgery had better OS than those who only received radiotherapy and/or chemotherapy. Endoscopic surgery had better OS than the open approach (p < 0.05). Microscopically margin-negative resection (R0 resection) significantly benefited OS and EFS (p < 0.001). No significant difference in OS was observed between patients who received macroscopic complete resection (R1 resection) followed by adjuvant therapy and patients who received R0 resection. Older age (HR = 1.02, p = 0.02), R1 resection (HR = 1.99, p = 0.02), sinonasal surgical history of more than 3 months before diagnosis (HR = 2.77, p = 0.007), and radiotherapy history (HR = 3, p = 0.006) are risk factors for worse EFS.ConclusionsCurative-intent surgery is irreplaceable in the treatment of SNM. The endoscopic approach is an effective alternative to the open approach. EFS is worse among patients with older age, R1 resection, sinonasal surgical history of more than 3 months before diagnosis, and radiotherapy history.

Background PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade. Materials and methods Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors. Results Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers. Conclusion CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.

Objective: To summarize the experience in diagnosis and treatment of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism and bilateral gonadoblastoma (Gb) secreting human chorionic gonadotrophin(HCG). Methods: A female patient aged 5 years and 3 months was admitted to the hospital with a complaint of "enlarged breasts for 27 months, and elevated blood β-HCG for 8 months". The clinical data were summarized, and related literature up to March 2022 with the key words"Turner syndrome" "Gonadoblastoma" "Y chromosome" "human chorionic gonadotropin" "precocious" in PubMed, CNKI and Wanfang databases were reviewed. Results: The girl went to the local hospital for 2-month breast development at age of 3 years, and was found with a heart murmur diagnosed with "pulmonary venous malformation and atrial septal defect (secondary foramen type)". Surgical correction was performed. She experienced the progressive breast development, rapid linear growth and markedly advanced skeletal age, which cannot be explained by partial activation in the hypothalamic-pituitary-gonadal axis determined at the age of 3 years and 7 months in local hospital. Then whole-exome sequencing revealed chromosome number abnormality 45, X, which was confirmed by Karyotyping. At the age of 4 years and 6 months, serum β-HCG was found to be elevated (24.9 U/L) with no lesion found at the local hospital. On physical examination, she was found with breast development, pubic hair development and clitoromegaly with elevated serum testosterone (1.96 μg/L) and β-HCG (32.3 U/L). Sex determining region Y(SRY) gene was negative in peripheral blood sample. Thoracic and abdominal CT, head and pelvic magnetic resonance imaging were normal. Exploratory laparotomy confirmed the presence of a left adnexal tumor and a right fibrous streak gonad. During surgery, simultaneous samples of bilateral gonadal and peripheral venous blood were obtained and serum β-HCG, estradiol and testosteron concentrations was higher to lower from left gonadal venous blood, right gonadal venous blood, to peripheral venous blood. Bilateral gonadectomy was performed. Histopathology revealed bilateral gonadoblastomas. SRY was positive in bilateral gonadal tissues. After surgery, serum E2, testerone and β-HCG returned to normal. So far 4 cases of HCG-secreting gonadoblastoma had been reported worldwide. The phenotypes of the 4 cases were all female, with virilization or amenorrhea, and the preoperative peripheral blood β-HCG concentrations were 74.4, 5.0, 40 456.0, and 42.4 U/L, respectively. Conclusions: There is a high risk of Gb in TS with Y chromosome components. Gb is infrequently presented with breast development, and Gb associated with HCG secretion is rare. Karyotyping should be performed in a phenotypic female with masculinization, and virilization in TS indicates the presence of Y chromosome material with concurrent androgen secreting tumors.

Abstract Study question Intraabdominal hemorrhage is a rare but serious complication following (oocyte pick up, OPU), it is very important for clinicians to know the risk factors. Summary answer Intraabdominal hemorrhage is mild in most cases, laparoscopy or laparotomy is the most effective approach to stop bleeding quickly in severe intraabdominal hemorrhage cases. What is known already During the OPU procedure, intraabdominal hemorrhage is not visible without the assistance of ultrasound, even minor bleeding, if persists, may lead to life-threatening consequences. Previous publications had limited sample size and the analysis of serial cases was scarce, most studies focused on severe hemorrhage that necessitated surgical interventions and somehow neglected those with mild hemorrhage. The reported incidence of severe intraabdominal hemorrhage varied from 0.06% to 0.27%, while 0.08%-0.1% of patients required surgery. Study design, size, duration Retrospective study, 25 cases that underwent post-OPU intraabdominal hemorrhage and required hospitalization in our center since 2003 to January 2021. Participants/materials, setting, methods Patients underwent intraabdominal hemorrhage following OPU in a University-affiliated center needed to be hospitalized. We aimed to discuss the clinical characteristics, risk factors, and precautionary measures of intraabdominal hemorrhage following OPU procedures. Main results and the role of chance The incidence of intraabdominal hemorrhage following OPU procedures was 0.044%. In all 25 cases, 17 received conservative treatment while emergency surgical exploration was performed to stop bleeding quickly for the remaining patients. Primary symptoms included the following: abdominal distention and/or pain, chest distress, dizziness, syncope, tenesmus, palpitations, etc.48% and 92% of patients had obvious symptoms within the first hour and 12 hours following OPU, respectively. Pelvic hematoma and/or effusion were found under ultrasonic scan in all but three patients. Overall, the reduction in hemoglobin(ΔHb) and hematocrit (ΔHct) were 26.50±13.32 g/L and 7.70%±3.66%, respectively. The mean interval between OPU and surgical procedure was 29.88±18.80 hours. And the main intra-operative findings were laceration and/or active bleeding on the ovary and satisfied hemostasis was achieved through suture or electrocoagulation. The blood aspirated during the procedure was 1 563±548 ml on average. Before they got discharged, these patients stayed at hospital for 5.04 days on average. In addition, our data shows that intraabdominal hemorrhage following OPU does not affect the final pregnancy outcomes, the cumulative live birth rate per woman was 48% (12/25). Limitations, reasons for caution This study is limited by its retrospective nature. In addition, patients who underwent mild hemorrhage and received effective therapy in an outpatient clinic rather than hospitalization or elsewhere were not included, which might lead to underestimation of the incidence concerned. Wider implications of the findings Intraabdominal hemorrhage is a rare but serious complication following OPU, which might be life-threatening. Nonetheless, hemorrhage is mild in most cases and conservative treatment is the first-line choice. Laparoscopy or laparotomy is the most effective approach to stop bleeding quickly in severe intraabdominal hemorrhage cases. Trial registration number not applicable

Objective: To investigate the localization methods of supratrochlear artery (STA) and supraorbital artery (SOA), and to explore the clinical benefit of locating nerve via accompanying vascular localization in combined transfrontal and intranasal endoscopic approaches. Methods: From June 2019 to May 2021, 14 patients, including 11 males and 3 females, aging from 18 to 69 years old, were underwent frontal sinus surgery through the combined transfrontal and intranasal endoscopic approaches in the Department of Otorhinolaryngology Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University. Before the surgery, localization of STA and SOA was determined by color doppler flow imaging (CDFI), computerized topographic angiography (CTA) and contrast enhanced magnetic resonance angiography (CE-MRA) respectively, and the distances between STA and SOA from facial midline were measured on 28 eyebrows. The position of external incision was determined according to the preoperative localization of STA and SOA. The examination time, cost and postoperative complications of the three methods were recorded. The accuracy of localization at 14 sides was verified by the surgery. GraphPad Prism 8.3 software was used for statistical analysis. Results: STA and SOA could be located by CDFI, CTA and CE-MRA. There was no significant difference in the measurement of the distance between STA and SOA from the facial midline among 3 methods (all P>0.05). Determining the position of external incision according to the localization of STA and SOA could protect both the blood vessels and accompanying nerves. No postoperative complications such as numbness of the forehead skin occurred. The measurement time of CDFI, CTA and CE-MRA was 22.50 (15.75, 30.00), 30.00 (28.00, 34.25) and 48.00 (44.00, 52.75) min (M (Q1, Q3)), respectively (all P<0.05). CDFI incurred the lowest costs and took the shortest time. Conclusions: CDFI is an efficient and economic localization method. The localization of STA and SOA facilitates the precise selection of the position of external incision, protects the accompanying nerve and reduces postoperative complications.

ObjectiveTo investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment.Materials and MethodsA list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein–protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient’s survival were analyzed using GEPIA, the Kaplan–Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells.ResultsAnalysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration.ConclusionsThe ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.

The tumor immune microenvironment plays an important role in head and neck squamous cell carcinoma (HNSCC). Reliable prognostic signatures able to accurately predict the immune landscape and survival rate of HNSCC patients are crucial to ensure an individualized/effective treatment. Here, we used HNSCC transcriptomic and clinical data retrieved from The Cancer Genome Atlas and identified differentially expressed immune-related long non-coding RNAs (DEirlncRNAs). DEirlncRNA pairs were recognized using univariate analysis. Cox and Lasso regression analyses were used to determine the association between DEirlncRNA pairs and the patients' overall survival and build the prediction model. Receiver operating characteristic curves and Kaplan-Meier survival curves were used to validate the prediction model. We then reevaluated the model based on the clinical factors, tumor-infiltrating immune cells, chemotherapeutic efficacy, and immunosuppression biomarkers. We built a risk score model based on 18 DEirlncRNA pairs, closely related to the overall survival of patients (hazard ratio: 1.376; 95% confidence interval: 1.302-1.453; P < 0.0001). Compared with two recently published lncRNA signatures, our DEirlncRNA pair signature had a higher area under the curve, indicating better prognostic performance. Additionally, the signature score positively correlated with aggressive HNSCC outcomes (low immunity score, significantly reduced CD8 + T cell infiltration, and low expression of immunosuppression biomarkers). However, high-risk patients might have high chemosensitivity. Overall, the lncRNAs signature established here shows promising clinical prediction and the effective disclosure of the tumor immune microenvironment in HNSCC patients; therefore, such signature might help distinguish patients that could benefit from immunotherapy.

Abstract How to treat clinically node-negative (cN0) neck in larynx squamous cell cancer (LSCC) has been subject to considerable discussion. The role of elective neck dissection (END) in patients with T3 glottic squamous cell cancer (GSCC) with cN0 is remain unclear. The objective of this study is to elucidate the role of END in improve the outcome of T3cN0M0 GSCC. Patients with T3cN0M0 GSCC in the Surveillance, Epidemiology, and End Results database (SEER) from 2004 to 2015 were extracted and stratified into END and Non-END cohorts, we found that only 22–58% T3cN0M0 GSCC were performed with END. After Propensity score matching (PSM), END cohort had better overall survival (OS) (median survival time: 93 vs 40 months, respectively; p < 0.0001) and cancer-specific survival (CSS) (HR 0.40, 95%CI 0.26 to 0.64, p = 0.0012) than non-END cohort. In addition, Subgroup analysis also indicated END cohort had better OS or CSS than non-END cohort.This study demonstrated that in patients with T3cN0M0 GSCC, END significantly associated with better survival outcomes compared with non-END.

Head and neck squamous cell carcinoma (HNSCC), the most frequent subtype of head and neck cancer, continues to have a poor prognosis with no improvement. The TNM stage is not satisfactory for individualized prognostic assessment and it does not predict response to therapy. In the present study, we downloaded the gene expression profiles from TCGA database to establish a training set and GEO database for a validation set. In the training set, we developed an 10 immune-related genes signature which had superior predictive value compared with TNM stage. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature might act as an independent factor for predicting the survival of HNSCC patients. As for the immune microenvironment, our results showed higher immune checkpoint expression (CLTA-4 and PD-1) in low-risk group which might reflect a positive immunotherapy response. Thus, our signature not only provided a promising biomarker for survival prediction, but might be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.

Controversial roles of interleukin-33 (IL-33) have been reported in melanoma from animal studies. We aimed to investigate the role of IL-33 in human cutaneous melanoma. RNA-seq data of 471 cases of cutaneous melanoma were retrieved from The Cancer Genome Atlas. The tumor microenvironment (TME) was deconstructed by the xCell algorithm using RNA-seq data. We evaluated the prognostic value of IL-33 and the relationship between IL-33 and immune components in TME. We also inferred the potential cellular sources of IL-33. All the analyses were conducted separately in three sub-cohorts, which are based on the biopsy sites of samples: primary melanoma; lymph node (LN) metastases; other metastases, including metastases to skin/soft tissue, or visceral sites. In the two metastasis sub-cohorts, IL-33 is associated with better prognosis and more active immune responses in the tumor. However, IL-33 is not a prognostic factor in the primary melanoma sub-cohort. Furthermore, we found that IL-33 is mainly derived from stromal cells in the metastasis sub-cohorts, and from epithelial cells/keratinocytes in the primary melanoma sub-cohort. These findings provide evidence for the context-specific anti-tumor effects of IL-33 in melanoma. And the distinct effects of IL-33 may be determined by the cellular sources of IL-33.

This study aimed to elucidate the role of elective neck dissection (END) in improving the outcome of T3cN0M0 glottic squamous cell cancer (GSCC).