Low Estradiol Level and Endometrial Thickness on the Day of Endometrial Transformation Influence Clinical Pregnancy After Intrauterine Insemination.

Background: The causes of pregnancy failure after intrauterine insemination (IUI) are controversial. The purpose of this study was to investigate the influencing factors on clinical pregnancy after IUI. Methods: This study retrospectively analyzed 1464 cycles of IUI performed at the Meizhou People's Hospital between March 2014 and June 2023. The χ2 test and logistic regression analysis was applied to assess the associations between the some factors (maternal age, paternal age, cycle type (natural cycle or ovulation induction cycle), hormone level on the day of endometrial transformation (estradiol (E2), luteinizing hormone (LH), and progesterone (P)), endometrial thickness on the day of endometrial transformation, and forward motile sperm concentration after treatment) and pregnancy failure. Results: Among the 1464 IUI cycles in this study, 268 cycles of assisted reproduction resulted in clinical pregnancy, with a clinical pregnancy rate of 18.3%. During the cycles with clinical pregnancy, there were 25 (12.9%) preterm births and 169 (87.1%) full-term births. The E2 level on the day of endometrial transformation in clinical pregnancy group was higher than that in the pregnancy failure group (658.79±656.02 vs 561.21±558.83 pg/mL)(P=0.025). The clinical pregnancy group had a higher percentage of endometrial thickness between 8 and 13mm on the day of endometrial transformation than the pregnancy failure group (83.2% vs 75.0%)(P=0.002). The results of regressions analysis showed that low E2 level on the day of endometrial transformation (<238.3 pg/mL vs ≥238.3 pg/mL: OR 1.493, 95% CI: 1.086-2.052, P=0.014), and endometrial thickness <8mm on the day of endometrial transformation (<8mm vs 8-13mm: OR 1.886, 95% CI: 1.284-2.771, P=0.001) may increase risk of pregnancy failure performed IUI. Conclusion: Low estradiol level, and endometrial thickness on the day of endometrial transformation may increase risk of pregnancy failure performed intrauterine insemination.

Peroxisome proliferator-activated receptors signature reveal the head and neck squamous cell carcinoma energy metabolism phenotype and clinical outcome.

BACKGROUND: Peroxisome proliferator activating receptors (PPARs) are important regulators of nuclear hormone receptor function, and they play a key role in biological processes such as lipid metabolism, inflammation and cell proliferation. However, their role in head and neck squamous cell carcinoma (HNSC) is unclear. METHODS: We used multiple datasets, including TCGA-HNSC, GSE41613, GSE139324, PRJEB23709 and IMVigor, to perform a comprehensive analysis of PPAR-related genes in HNSC. Single-cell sequencing data were preprocessed using Seurat packets, and intercellular communication was analyzed using CellChat packets. Functional enrichment analysis of PPAR-related genes was performed using ClusterProfile and GSEA. Prognostic models were constructed using LASSO and Cox regression models, and immunohistochemical analyses were performed using human protein mapping (The Human Protein Atlas). RESULTS: Our single-cell RNA sequencing analysis revealed distinct cell populations in HNSC, with T cells having the most significant transcriptome differences between tumors and normal tissues. The PPAR features were higher in most cell types in tumor tissues compared with normal tissues. We identified 17 PPAR-associated differentially expressed genes between tumors and normal tissues. A prognostic model based on seven PPAR-associated genes was constructed with high accuracy in predicting 1, 2 and 3 year survival in patients with HNSC. In addition, patients with a low risk score had a higher immune score and a higher proportion of T cells, CD8+ T cells and cytotoxic lymphocytes. They also showed higher immune checkpoint gene expression, suggesting that they might benefit from immunotherapy. PPAR-related genes were found to be closely related to energy metabolism. CONCLUSIONS: Our study provides a comprehensive understanding of the role of PPAR related genes in HNSC. The identified PPAR features and constructed prognostic models may serve as potential biomarkers for HNSC prognosis and treatment response. In addition, our study found that PPAR-related genes can differentiate energy metabolism and distinguish energy metabolic heterogeneity in HNSC, providing new insights into the molecular mechanisms of HNSC progression and therapeutic response.

Identification and validation of a 9-gene signature for the prognosis of ovarian cancer by integrated bioinformatical analysis.

Background: Ovarian cancer (OC) is the most lethal malignancy among gynecological cancers worldwide. It is urgent to identify effective biomarkers for the prognosis and diagnosis of OC. Methods: We analyzed 4 OC Gene Expression Omnibus (GEO) data sets to detect differentially expressed genes (DEGs). To explore potential correlations between the gene sets and clinical features, we conducted weighted gene co-expression network analysis (WGCNA). Hub genes were identified from the key modules by univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses and risk scores were calculated based on the expressions of the hub genes. Univariate and multivariate Cox regression analyses were conducted to determine the values of the diagnoses for OC patients. We also determined the predictive value of the long non-coding RNA (lncRNA) score in response to immunotherapy and chemotherapeutic drugs. Results: DEGs were analyzed between the OC and normal ovarian tissues and prognostic modules were identified by a WGCNA. Nine hub genes chose from the prognostic modules were determined the prognostic values in OC. The risk scores were calculated based on the expression of hub genes, and patients with high-risk scores had poor survival. Univariate and multivariate Cox regression analyses showed that the risk score was an independent prognostic factor for OC. Additionally, the levels of hub genes were also found to be related to immune cell infiltration in OC microenvironments. An immunotherapy cohort showed that high-risk scores enhanced the response to anti-programmed death-ligand 1 (PD-L1) immunotherapy and was remarkably correlated with the inflamed immune phenotype, and had significant therapeutic advantages and clinical benefits. Further, patients with high-risk scores were more sensitive to midostaurin. Conclusions: We identified the risk score including protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K), protein phosphatase 1 catalytic subunit alpha (PPP1CA), exostosin glycosyltransferase 1 (EXT1), RAB GTPase activating protein 1 like (RABGAP1L), mitotic arrest deficient 2 like 1 (MAD2L1), xeroderma pigmentosum complementation group C (XPC), Egl-9 family hypoxia inducible factor 3 (EGLN3), cyclin D1 binding protein 1 (CCNDBP1), and zinc finger protein 25 (ZNF25), and validated their prognostic and predicted values for OC.

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells.

Ubiquitin-proteasome pathway has emerged as therapeutic targets for cancer. GEPIA database analysis showed that the expression of ubiquitin-associated protein 2 like (UBAP2L) in gastric cancer specimens was significantly higher than that in non-tumor tissue, and its high expression is associated with poor survival of gastric cancer patients. This study aims to investigate the role of UBAP2L in gastric cancer. Real-time PCR and western blot results showed that UBAP2L expression was upregulated in gastric cancer cell lines. Loss- and gain-of-function experiments demonstrated that silencing of UBAP2L inhibited proliferation, migration and invasion, and induced apoptosis of gastric cancer cells, and overexpression of UBAP2L played opposite roles. Nude mice inoculated with UBAP2L-silenced gastric cancer cells generated smaller xenografted tumors in vivo. Furthermore, UBAP2L activated Wnt/ß-catenin signaling - the accumulation of nuclear ß-catenin and the expression of its downstream targets (cyclin D1, AXIN-2 and c-MYC) was facilitated, whereas knockdown of UBAP2L deactivated this signaling. The tumor-suppressing effect of UBAP2L silencing was abolished by forced activation of ß-cateninS33A. UBAP2L has been confirmed as a novel and direct target of miR-148b-3p. The anti-tumor effect of miR-148b-3p was partly reversed by UBAP2L overexpression. The expression of miR-148b-3p was negatively correlated with that of UBAP2L in gastric cancer samples. Overall, our study indicates that UBAP2L is required to maintain malignant behavior of gastric cancer cells, which involves the activation of Wnt/ß-catenin signaling pathway. We propose UBAP2L as a potential therapeutic target against gastric cancer.

Knockdown of miR­205­5p alleviates the inflammatory response in allergic rhinitis by targeting B­cell lymphoma 6.

Allergic rhinitis (AR) is an IgE­mediated upper airway disease with a high worldwide prevalence. MicroRNA (miR)­205­5p upregulation has been observed in AR; however, its role is poorly understood. The aim of the present study was to investigate the effect of miR­205­5p on AR­associated inflammation. To establish an AR model, BALB/c mice were sensitized using an intraperitoneal injection of ovalbumin (OVA) on days 0, 7 and 14, followed by intranasal challenge with OVA on days 21­27. A lentiviral sponge for miR­205­5p was used to downregulate miR­205­5p in vivo via intranasal administration on days 20­26. Reverse transcription­quantitative PCR revealed that miR­205­5p was upregulated in AR mice. Notably, miR­205­5p knockdown reduced the frequency of nose­rubbing and sneezing, and attenuated pathological alterations in the nasal mucosa. The levels of total and OVA­specific IgE, cytokines IL­4, IL­5 and IL­13, and inflammatory cells, were decreased by miR­205­5p knockdown in AR mice. In addition, miR­205­5p knockdown inhibited nucleotide­binding oligomerization domain­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome activation by reducing the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, cleaved caspase­1 and IL­1ß by western blot analysis. B­cell lymphoma 6 (BCL6) was confirmed as a target of miR­205­5p by luciferase reporter assay. In conclusion, the present findings suggested that miR­205­5p knockdown may attenuate the inflammatory response in AR by targeting BCL6, which may be a potential therapeutic target for AR.

Meta-analysis of clinical trials on traditional Chinese herbal medicine for treatment of persistent allergic rhinitis.

BACKGROUND: Chinese herbal medicine (CHM) has been used for the prevention and treatment of persistent allergic rhinitis (PAR), but results are still equivocal. This study was to assess the clinical effectiveness of CHM in patients with PAR. MATERIALS AND METHODS: Databases searched included articles published in the Cochrane library, MEDLINE, EMBASE, China National Knowledge Infrastructure, and Wanfang database from 1999 to 2011. The studies included were randomized controlled trials (RCTs) comparing CHM to placebo if they included patients with PAR. The main outcomes were the changes in the standardized mean difference (SMD) of nasal symptom scores and total serum IgE level. Methodological quality was assessed by the modified Jadad's scale. RESULTS: Seven RCTs with 533 patients were identified and analyzed. In the meta-analysis, CHM reduced the total nasal symptom scores compared to placebo (SMD, -1.82; 95% confidence interval [CI], -3.03 to -0.62; P = 0.003). The effect estimate was in favor of the CHM intervention (SMD, -1.09; 95% CI, -2.74 to 0.55) in reducing the total serum IgE level, although this was not significant (P = 0.19). CONCLUSIONS: CHM interventions appear to have beneficial effects in patients with PAR. However, the published efficacy studies are too small to draw firm conclusion.

[Relationship among expression of the VEGF gene and MVD with cervical lymph nodes metastasis in laryngeal squamous cell carcinoma].

OBJECTIVE: To study the relation among the expression of the vascular endothelial growth factor (VEGF) gene and microvessel Density (MVD) with cervical lymph nodes metastasis in laryngeal squamous cell carcinoma (LSCC). METHOD: Appling semi-RT-PCR technique and immunohistochemistry detected the expression of VEGFmRNA and protein and MVD count in 60 cases with LSCC. RESULT: The expression of VEGF and MVD was both higher either at molecular level or at the protein level in the group with cervical lymph nodes metastasis than the those with cervical lymph nodes-negative metastasis. The overexpression of VEGF had a positive correlation with the higher MVD count and were both related to cervical lymph nodes metastasis in the 60 cases with LSCC. CONCLUSION: There was a significant correlation between the expression of VEGF and MVD, which suggested that the overexpression of VEGF was essential to microangiogenesis of LSCC, and the both were related to cervical lymph nodes metastasis and would become a biologic indexes to prognosis of LSCC. Antiangiogenic therapy with specific antibodies to VEGF leads to inhibit angiogenesis and prevent tumor from growth and metastasis, which might have a bright future in clinical application.

[Expression of the metastasis-associated gene 1 in laryngeal squamous cell carcinoma: correlation with cervical lymph node metastasis].

OBJECTIVE: The purpose of study was to examine the mRNA expression levels of the metastasis-associated gene1 (MTA1) in laryngeal squamous cell carcinoma (LSCC), so to evaluate its relationship with metastases. METHODS: Forty-eight surgically resected primary LSCC (16 supraglotti laryngeal carcinomas with cervical lymph node metastasis, 16 supraglotti laryngeal carcinomas with cervical lymph node-negative metastasis, 16 glottic carcinoma with cervical lymph node-negative metastasis) and 16 normal laryngeal mucosa was examined for mRNA expression of MTA1 by reverse transcription-polymerase chain reaction(RT-PCR). RESULTS: The frequency of MTA1 mRNA positive expression in 16 LSCC with cervical lymph node metastasis was 100%, but no expression of MTA1 mRNA was observed in other LSCC with cervical lymph node-negative metastasis (16 supraglotti laryngeal carcinomas and 16 glottic carcinoma) and 16 normal laryngeal mucosa. CONCLUSION: MTA1 gene is strongly related to cervical lymph node metastasis of LSCC, and may serve as a early diagnosis indicator.