H3K27me3 Inactivates SFRP1 to Promote Cell Proliferation via Wnt/ß-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Histone methylations are generally considered to play an important role in multiple cancers by regulating cancer-related genes. AIMS: This study aims to investigate the effects of H3K27me3-mediated inactivation of tumor suppressor gene SFRP1 and its function in esophageal squamous cell carcinoma (ESCC). METHODS: We performed ChIP-seq on H3K27me3-enriched genomic DNA fragments in ESCC cells to screen out tumor suppressor genes that may be regulated by H3K27me3. ChIP-qPCR and Western blot were employed to explore the regulating mechanisms between H3K27me3 and SFRP1. Expression level of SFRP1 was assessed by quantitative real-time polymerase chain reaction (q-PCR) in 29 pairs of ESCC surgical samples. SFRP1 function in ESCC cells were detected by cell proliferation assay, colony formation assay and wound-healing assay. RESULTS: Our results indicated that H3K27me3 was widely distributed in the genome of ESCC cells. Specifically, we found that H3K27me3 deposited on the upstream region of SFRP1 promoter and inactivated SFRP1 expression. Furthermore, we found SFRP1 was significantly down-regulated in ESCC tissues compared with the adjacent non-tumor tissues, and SFRP1 expression was significantly associated with TNM stage and lymph node metastasis. In vitro cell-based assay indicated that over-expression of SFRP1 significantly suppressed cell proliferation and negatively correlated with the expression of ß-catenin in the nucleus. CONCLUSIONS: Our study revealed a previously unrecognized finding that H3K27me3-mediated SFRP1 inhibit the cell proliferation of ESCC through inactivation of Wnt/ß-catenin signaling pathway.

[Pelvic floor muscle rehabilitation training combined with psychological nursing intervention in the treatment of type â ¢B prostatitis].

OBJECTIVE: To investigate the clinical effect of pelvic floor muscle rehabilitation training combined with psychological nursing intervention in the treatment of intractable type ⅢB prostatitis. METHODS: We retrospectively analyzed the clinical data on 51 cases of intractable type ⅢB prostatitis treated from October 2020 to October 2022, which were randomly assigned to receive Tamsulosin medication (the control group, n = 24) or pelvic floor muscle rehabilitation training and psychological nursing in addition (the intervention group, n = 27), all for 8 weeks. We obtained NIH-CPSI, IIEF-5, Self-Rating Anxiety Scale (SAS) scores, Self-Rating Depression Scale (SDS) scores, the level of lecithin and the count of leukocytes in the prostatic fluid and the incidence of adverse events, and compared them between the two groups of patients before and after treatment. RESULTS: The total effectiveness rate was significantly higher in the intervention than in the control group (88.9% vs 62.5%, P < 0.05). Compared with the baseline, the NIH-CPSI, IIEF-5, SAS and SDS scores and the lecithin level were remarkably increased in both groups after treatment (P < 0.05), even more significantly in the intervention group than in the control (P < 0.05). No statistically significant difference was observed in the count of leukocytes before and after treatment (P > 0.05). CONCLUSION: On the basis of Tamsulosin medication, the application of pelvic floor rehabilitation training combined with psychological care can significantly enhance the therapeutic effect on type IIIB prostatitis, effectively relieve prostatitis pain, improve erectile function, lessen anxiety and depression symptoms, increase the level of lecithosomes and promote the recovery of prostatic function.

Prevalence of human papillomavirus infection of 65,613 women in East China.

BACKGROUND: The infection with human papillomavirus (HPV) is the major cause of genital disease. This study assessed the prevalence and genotype of HPV among outpatient women and healthy women in Jiangsu, East China. METHODS: A total of 65,613 women aged 16-85 years were recruited from Nanjing Kingmed Diagnostics, including 45,736 outpatients and 19,877 healthy women. The cervico-vaginal cells were collected and then HPV types were detected using the Tellgenplex™ HPV DNA Test. RESULTS: The overall HPV prevalence was 17.7% for outpatients and 10.6% for healthy women. 13.7% outpatients were infected with a single HPV type and 4.0% were infected with multiple HPV types. Regarding healthy women, 8.5 and 2.1% were infected with single and multiple HPV types, respectively. The two most commonly detected HPV types were HPV 16 and 58 regardless of single- or multiple-type infection or source of the participants. HPV16 + 58 was the most commonly identified multiple genotype in outpatients, while HPV16 + 52 was frequently detected in healthy women. Highest prevalence rate was found in outpatients aged < 20 years and ≥ 60 years. CONCLUSIONS: This study revealed the prevalence characteristics of HPV in both outpatient women and healthy women in Jiangsu province.

HBx increases chromatin accessibility and ETV4 expression to regulate dishevelled-2 and promote HCC progression.

Hepatitis B virus (HBV) infection is the predominant causes of hepatocellular carcinoma (HCC). HBV X protein (HBx), as the most frequently integrated viral gene sequence following HBV infection, plays a critical role in the pathogenesis of HCC. H3K27ac is a characteristic marker for identifying active enhancers and even indicates chromatin accessibility associated with super-enhancers (SEs). In this study, H3K27ac ChIP-seq was applied for high-quality SE annotation of HBx-induced SEs and chromatin accessibility evaluation. The results indicated that HBx preferentially affects enrichment of H3K27ac in transcription factor signaling pathway genes, including ETV4. RNA-seq indicated that ETV4 is upregulated by HBx and that upregulated ETV4 promotes HCC progression. Interestingly, ETV4 was also included in the 568 cancer driver gene pool obtained by the Integrative OncoGenomics pipeline. However, the biological function and mechanism of ETV4 remain incompletely understood. In vivo and in vitro, we found that increased ETV4 expression promotes HCC cell migration and invasion by upregulating DVL2 and activating Wnt/ß-catenin. The mRNA and protein levels of ETV4 are higher in tumor tissues compared with adjacent tissues, and high expression of ETV4 is associated with poor prognosis in HCC patients. In summary, we first confirm that ETV4 is significantly upregulated by HBx and involved in SE-associated chromatin accessibility. Increased expression of ETV4 promotes HCC cell invasion and metastasis by upregulating DVL2. The present study provides insight into the ETV4-DVL2-ß-catenin axis in HBV-related HCC, which will be helpful for treating patients with aggressive HCC.

Prognostic value of PD-L1 expression combined with hypoxia-associated immunosuppression in hepatocellular carcinoma.

Background: Hypoxia and immunosuppression are two properties of cancer. This study intends to establish the potential relationship between these two hallmarks in hepatocellular carcinoma (HCC). Materials & methods: A bioinformatics analysis of data obtained from the Cancer Genome Atlas and a retrospective single-center analysis based on a tissue microarray were utilized in this study. Results: We identified a hypoxia-high subtype of patients with immunosuppressive HCC which represented a poor prognosis in the Cancer Genome Atlas cohort. Immunohistochemical analysis of the tissue microarray showed that tumor PD-L1 expression was positively linked to HIF-1α expression, pro-tumor immunocyte infiltration and poor survival in HCC patients. Conclusion: This study provides evidence supporting the correlation between hypoxic signals and immunosuppression in HCC; the combined use of them might improve survival prediction and act as a potential predictor for PD-1/PD-L1 therapy.

Thyroglossal duct cyst with hoarseness as the sole symptom and an intralaryngeal extension masquerading as a laryngeal mass: Clinical experience and literature review.

A thyroglossal duct cyst is the most common congenital disease in the neck. There are two age groups usually associated with thyroglossal duct cysts: 1-11 years in children and 30-60 years in adults. These midline neck masses are typically located anteriorly in the neck, inferior to the hyoid bone. We report an extremely rare case of an intralaryngeal thyroglossal duct cyst without a neck mass, presenting with hoarseness as the sole symptom. A 64-year-old man presented with a 3-month history of hoarseness. On physical examination, no neck mass or swelling was observed during cervical palpation. Laryngostroboscopy revealed a large submucosal mass in the right glottis and supraglottis, and mobility of the right vocal cord was restricted. Surgery was performed via an external approach to completely resect the cyst, together with the middle part of the hyoid bone. Histopathologic examination of the cyst led to a diagnosis of thyroglossal duct cyst. The patient recovered well and his voice returned to normal. Attention should be paid to the occurrence of rare types of thyroglossal duct cyst in unusual clinical sites. Adequate radiological examinations should be performed, and reading the computed tomography or magnetic resonance imaging scans carefully before surgery is important to avoid misdiagnosis.

Clinical Features and Influencing Factors for the Prognosis of Patients With Sudden Deafness.

Backgrounds: Studies on risk factors influencing the prognosis of patients with sudden onset deafness are lacking. Methods: From March 2018 to March 2021, 500 patients, from the Tongde Hospital in Zhejiang Province, with sudden onset deafness were enrolled. We collected clinical information from the hospital medical records, including certain demographic characteristics, information related to sudden-onset deafness, and laboratory parameters. Univariate and multivariate analyses were performed to determine independent prognostic risk factors for patients with sudden deafness. Additionally, we also employed orthogonal partial least squares discriminant analysis (OPLS-DA) to analyze the data of these enrolled patients. Results: The baseline clinical characteristics of the enrolled patients were analyzed. Based on their prognoses, the included patients were divided into the overall effective and ineffective groups. Between these two groups, the univariate and multivariate analyses were performed. Age, type of hearing curve at the initial diagnosis, acute phase, and sudden deafness site were found to be independently associated with the prognoses of patients with sudden deafness (all P < 0.05). Through the OPLS-DA, the sudden deafness site was found to be an indicator with the highest predictive power. Conclusions: Age, type of hearing curve at the initial diagnosis, acute phase, and sudden deafness site were all independently correlated with the prognoses of patients with sudden deafness and, therefore, need to be emphasized.

Elevated LncRNA TRERNA1 correlated with activation of HIF-1α predicts poor prognosis in hepatocellular carcinoma.

BACKGROUND: Translation regulatory long non-coding RNA 1 (TRERNA1) has been reported to be upregulated in several cancers and accelerate tumor metastasis by inducing epithelial-to-mesenchymal transition (EMT). However, it remains unclear how TRERNA1 is upregulated and whether the upregulation of TRERNA1 influences the prognosis of HCC patients. In this study, we aimed to investigate the prognostic value of TRERNA1 in HCC and the regulatory mechanism underlying TRERNA1 upregulation. METHODS: In situ hybridization was adopted to analyze the expression level of TRERNA1, and immunohistochemistry technique was employed to evaluate the expression level of HIF-1α and E-cadherin. χ2 test was used to assess the association between TRERNA1 level and clinicopathological characteristics of HCC cases, whereas Kaplan-Meier survival analysis, ROC curve analysis and Cox proportional hazards regression model were performed to evaluate the prognostic significance of TRERNA1 expression level in HCC. RESULTS: TRERNA1 was substantially upregulated in HCC tissues, which was accompanied by aberrant decreased expression of E-cadherin. Elevated TRERNA1 level was correlated with high tumor grade, high recurrence rate and poor survival in patients with HCC. Moreover, TRERNA1 expression level was positively correlated with the activation of HIF-1α. Importantly, high TRERNA1 expression level can be an independent risk factor for poor prognosis in HCC, especially combining elevated TRERNA1 and HIF-1α with decreased E-cadherin predicted a worst prognosis of patients with HCC. CONCLUSION: TRERNA1 is not only a biomarker for predicting poor prognosis in HCC patients, but also can categorize HCC patients into different risk groups for survival when combined with HIF-1α and E-cadherin.

Immune cell infiltration and related core genes expression characteristics in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) refers to chronic inflammation of the sinonasal mucosa. It can either be eosinophilic (ECRSwNP) or non-eosinophilic (non-ECRSwNP). However, immune cell infiltration in the microenvironment and pathogenesis of ECRSwNP and non-ECRSwNP are still unclear. The aim of the present study was to assess the immune cell infiltration and molecular mechanisms of ECRSwNP and non-ECRSwNP. In the present study, 22 immune cell types in ECRSwNP and non-ECRSwNP were investigated by CIBERSORT based on transcriptome data. The core gene related pathophysiology of CRSwNP was analyzed using Weighted Gene Correlation Network Analysis according to the phenotype of the infiltrated eosinophils and nasal polyps (NP). A total of four types of immune cells (mast cells, activated dendritic cells, M2 macrophages and activated natural killer cells) were demonstrated to have a direct and indirect correlation with eosinophilic infiltration in ECRSwNP. M1 macrophages and activated CD4+ memory T cells were correlated with major immune cell types in non-ECRSwNP. NP could affect the expression of 'olfactory receptor activity' and 'channel activity' genes to impair the olfactory signaling pathway and neuroactive ligand receptor pathway. 'Cell adhesion molecule binding', 'cytokine receptor binding' and 'glucocorticoid receptor binding' were significantly enriched in ECRSwNP, whereas epithelial cell injury, autophagy and the mTOR pathway (hsa04140 and hsa04150) may serve an important role in the pathogenesis of non-ECRSwNP. There were significantly different immune cell infiltration and related core genes expression characteristics between ECRSwNP and non-ECRSwNP. The results of the present study provide an improved basis for elucidation of the mechanism and treatment of CRSwNP.

Long non-coding RNA LINC00460 promotes head and neck squamous cell carcinoma cell progression by sponging miR-612 to up-regulate AKT2.

LncRNAs (long noncoding RNAs) have been shown to be potentially critical regulators in head and neck squamous cell carcinoma (HNSCC). LncRNA LINC00460 (long intergenic non-protein coding RNA 460), an "oncogene", regulates progression of various tumors. However, the tumorigenic mechanism of LINC00460 on HNSCC is yet to be investigated. In the current study, we discovered that LINC00460 was relatively up-regulated in both HNSCC cancer tissues and cell lines, and predicted a poor prognosis in HNSCC patients. Gain- and loss-of functional studies established that over-expression of LINC00460 promoted cell proliferation, invasion and migration of HNSCC cells in vitro, while the promotion abilities were suppressed via knockdown of LINC00460. Our results identified miR-612 as a novel target of LINC00460, whose expression suggested a negative correlation with LINC00460 in HNSCC tissues and cell lines. LINC00460 increased the expression of serine/threonine kinase AKT2 via sponging miR-612. Rescue experiments indicated that LINC00460 could promote HNSCC progression partially through inhibition of miR-612. Subcutaneous xenotransplanted tumor model confirmed that interference of LINC00460 suppressed in vivo tumorigenic ability of HNSCC via down-regulation of AKT2. In conclusion, our findings clarified the biologic significance of LINC00460/miR-612/AKT2 axis in HNSCC progression and provided novel evidence that LINC00460 may be a new potential therapeutic target for HNSCC.

A Large Cohort Study on the Clinical Value of Simultaneous Amplification and Testing for the Diagnosis of Pulmonary Tuberculosis.

The AmpSure simultaneous amplification and testing method for the detection of Mycobacterium tuberculosis (SAT-TB assay) was designed to diagnose rapidly pulmonary tuberculosis (PTB). Unfortunately, the diagnostic advantage is unclear from previous small sample studies. In the current inquiry, a large sample size was used to reevaluate the clinical accuracy of the SAT-TB assay using sputum specimens. A total of 3608 patients with suspected PTB were enrolled prospectively for diagnosis from sputum specimens using the SAT-TB assay. Of these, 2457 had a definite diagnosis of PTB confirmed by positive microbiology, or pathologic findings of TB in the lung, or clinical diagnosis of active PTB following anti-TB treatment with a favorable response. The sensitivity, specificity and accuracy of the SAT-TB assay were 75.8%, 100%, and 80.2%, respectively. The sensitivity of SAT-TB was significantly higher than that of the sputum smear (23.8%) (X(2) = 1327.437; P = 0.000), wheresa significantly lower than that of sputum culture (89.0%) (X(2) = 148.197; P = 0.000). The specificity of SAT-TB was significantly higher than that of sputum smears (96.3%) (X(2) = 20.375, P = 0.000), whereas no significant difference was found compared with sputum cultures (99.6%) (X(2) = 2.004, P = 0.500). Positive results in the SAT-TB assay using sputum specimens indicates that active PTB is present and anti-TB treatment is strongly recommended regardless of smear and culture test results. Simultaneous amplification and testing method for detection of Mycobacterium tuberculosis is an accurate, cheap, and rapid method for PTB diagnosis.

Prognostic factors of tuberculous meningitis: a single-center study.

OBJECTIVE: To investigate the prognostic factors of tuberculous meningitis (TBM) and develop strategies for the improvement of clinical efficacy. METHODS: A total of 156 TBM patients were retrospectively reviewed. The demographic characteristics, underlying diseases, clinical features, laboratory findings, bacteriologic test, images, use of steroids, mannitol and anti-TB drugs, surgery or drainage, and clinical outcomes were collected and analyzed. RESULTS: Patients with tubercle bacillus in the cerebrospinal fluid had significantly higher rate of consciousness disturbance (78.8%) and greater proportion of Glasgow coma scale (GCS) score of 3 (37.9%) when compared with the possible TBM patients (51.1% and 13.3%, respectively). Patients with definite TBM had a poor outcome and their mortality was significantly higher than in possible TBM patients (42.4% vs. 17.8%, P < 0.05). Univariate regression analysis showed that the advanced age, concomitant hematogenous disseminated pulmonary tuberculosis, change in consciousness, low GCS score on admission and hydrocephalus were associated with a poor prognosis; timely anti-TB treatment and reasonable hormone applications predicted a favorable outcome. Multivariate regression analysis showed that advanced age, change in consciousness, low GSC score and concomitant hydrocephalus were independent risk factors of TBM, and use of prednisone at ≥ 60 mg/d was protective factor for TBM (P=0.003, OR=0.013). CONCLUSIONS: The advanced age, changes in consciousness, low GCS score on admission and concomitant hydrocephalus are independent risk factors of TBM. For patients with risk factors, diagnostic anti-TB therapy and reasonable hormone therapy should be performed timely to reduce mortality and disability.

Diversities of interaction of murine macrophages with three strains of Candida albicans represented by MyD88, CARD9 gene expressions and ROS, IL-10 and TNF-α secretion.

AIM: To explore the mechanisms underlying the different responses of macrophages to distinct Candida albicans strains. METHODS: Bone marrow was collected from mice. Macrophages were independently incubated with 3 Candida albicans strains. RESULTS: MyD88 expression in Candida albicans 3683 group was significantly higher than that in Candida albicans 3630 group and Candida albicans SC5314 group, and marked difference was also observed between later two groups (P<0.05). CARD9 expression in Candida albicans 3630 group was higher than that in Candida albicans 3683 group and Candida albicans SC5314 group. Fluorescence intensity was 46.78±0.79 in Candida albicans 3630 group, 32.60±1.31 in Candida albicans 3683 group and 19.40±0.58 in Candida albicans SC5314, and significant difference was observed between any two groups (P<0.05). TNF-α and IL-10 were 18.9843±0.7081 pg/ml and 11.6690±0.3167 pg/ml, respectively, in Candida albicans 3683 group, which were markedly higher than those in Candida albicans 3630 group and Candida albicans SC5314 group (P<0.05 and 0.01). CONCLUSION: Different Candida albicans strains may induce CARD9 expression and alter the production of ROS, TNF-α and IL-10 in macrophages, which may be one of mechanisms underlying the different killing effects of macrophages on distinct Candida albicans strains.

Immunisation with the glycolytic enzyme enolase confers effective protection against Candida albicans infection in mice.

Candida albicans is an opportunistic human fungal pathogen that continues to be a leading cause of candidal infections in immunocompromised hosts. Enolase, an important glycolytic enzyme located on the cell wall of C. albicans, was cloned, purified, and characterized by molecular cloning, affinity chromatography and Western blotting. C57BL/6J mice were immunized with recombinant enolase subcutaneously every two weeks, and the protective effect against systemic challenge evaluated by fungal burdens in target organs, titres of specific antibodies to enolase, and by levels of Th1/2 cytokines in serum. After challenge with C. albicans strains SC5314 and 3630, fungal burdens in the liver, kidney, brain, spleen and lung were significantly decreased in immunized mice. Histopathological assessment demonstrated that enolase protected the tissue structure, and decreased the infiltration of inflammatory cells. The titres of enolase-specific IgG1 and IgG2a in the immune serum reached up to 1:51200. Furthermore, opsonization with immune serum resulted in enhanced killing of both 3630 and SC5314 by murine neutrophils. Levels of IL-12 and IL-8 in the immune serum increased, whereas the concentration of the Th2 cytokine, IL-10, was significantly higher in immunized mice compared to the control group. It was concluded that recombinant enolase effectively protected mice against disseminated candidiasis, and may be a promising target for vaccination against different strains of C. albicans.