Day 4 and day 0 neutrophil-to-lymphocyte ratios as predictors of treatment failure with single-dose methotrexate for ectopic pregnancies.

OBJECTIVE: To evaluate changes in the neutrophil-to-lymphocyte ratio (NLR) between day 4 and day 0 in ectopic pregnancy (EP) patients treated with single-dose methotrexate (MTX) and investigate its predictive value for treatment outcome. METHODS: A total of 406 EP patients receiving single-dose MTX therapy at Shanghai First Maternity and Infant Hospital from January 10, 2013 to September 30, 2019 were studied. A multivariate model was constructed to predict treatment outcome. RESULTS: Among the 406 patients, 281 were treated successfully. Treatment success declined significantly when NLR decreased by less than 23% (74.8% vs 58.5%, P = 0.004). Multivariate regression analysis identified NLR reduction of less than 23% on day 4 (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.27-3.44), a human chorionic gonadotropin (hCG) decrease of 15% or less (OR 3.17, 95% CI 1.62-6.34), and an hCG increase of more than 15% on day 4 (OR 5.47, 95% CI 3.05-10.22) as independent risk factors for single-dose MTX treatment failure. The final predictive model had a sensitivity of 0.768 and a specificity of 0.569, using a cut-off value of 3. The area under the receiver operating characteristic curve was 0.712. Patients with a predictive score of ≥3 were more likely to fail single-dose MTX therapy. CONCLUSION: The present study concluded that an NLR decrease of less than 23% on day 4, a plateau or increase in serum hCG on day 4, and an hCG value greater than 1000 mIU/mL on day 0 were predictors of single-dose MTX treatment failure in EP patients.

Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m 6A-dependent miR-17-5p maturation-induced ZBTB4 depletion.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aim to investigate the role and molecular mechanisms of the demethylase FTO (fat mass and obesity-associated protein) in TNBC. Through analysis of public databases, we identify that FTO may regulate the maturation of miR-17-5p and subsequently influence the expression of zinc finger and BTB domain-containing protein 4 (ZBTB4), thereby affecting the occurrence and progression of TNBC. We screen for relevant miRNAs and mRNAs from the GEO and TCGA databases and find that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrate that overexpression of FTO can suppress the proliferation, migration, and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m 6A-dependent mechanism. Furthermore, we establish a xenograft nude mouse model and collect clinical samples to further confirm the role and impact of the FTO/miR-17-5p/ZBTB4 regulatory axis in TNBC. Our findings unveil the potential role of FTO and its underlying molecular mechanisms in TNBC, providing new perspectives and strategies for the research and treatment of TNBC.

Prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with breast cancer treated with neoadjuvant chemotherapy: a meta-analysis.

OBJECTIVE: Platelet-to-lymphocyte ratio (PLR), known as a key systemic inflammatory parameter, has been proved to be associated with response to neoadjuvant therapy in breast cancer (BC); however, the results remain controversial. This meta-analysis was carried out to evaluate the prognostic values of PLR in patients with BC treated with neoadjuvant chemotherapy (NACT). DESIGN: Meta-analysis. DATA SOURCES: Relevant literature published on the following databases: PubMed, Embase, Web of Science databases and the Cochrane Library. ELIGIBILITY CRITERIA: All studies involving patients with BC treated with NACT and peripheral blood pretreatment PLR recorded were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted and evaluated HR/OR and its 95% CI of survival outcomes, pathological complete response (pCR) rate and clinicopathological parameters. RESULTS: The last search was updated to 31 December 2022. A total of 22 studies with 5533 patients with BC treated with NACT were enrolled in the final meta-analysis. Our results demonstrate that elevated PLR value appears to correlate with low pCR rate (HR 0.77, 95% CI 0.67 to 0.88, p<0.001, I2=75.80%, Ph<0.001) and poor prognosis, including overall survival (OS) (HR 1.90, 95% CI 1.39 to 2.59, p<0.001; I2=7.40%, Ph=0.365) and disease-free survival (HR 1.97, 95% CI 1.56 to 2.50, p<0.001; I2=0.0%, Ph=0.460). Furthermore, PLR level was associated with age (OR 0.86, 95% CI 0.79 to 0.93, p<0.001, I2=40.60%, Ph=0.096), menopausal status (OR 0.83, 95% CI 0.76 to 0.90, p<0.001, I2=50.80%, Ph=0.087) and T stage (OR 1.05, 95% CI 1.00 to 1.11, p=0.035; I2=70.30%, Ph=0.005) of patients with BC. CONCLUSIONS: This meta-analysis demonstrated that high PLR was significantly related to the low pCR rate, poor OS and disease-free survival (DFS) of patients with BC treated with NACT. Therefore, PLR can be used as a potential predictor biomarker for the efficacy of NACT in BC.

Three-Dimensional Anatomy of the Hypoglossal Canal: A Plastinated Histologic Study.

OBJECTIVE: To provide a precise description of the morphology and morphometry of the hypoglossal canal (HC) and its relationship with surrounding structures by using the epoxy sheet plastination technique. METHODS: Thirty human cadaveric heads were plastinated into 5 sets of gross transparent plastination slices and 43 sets of ultrathin plastination sections. The HC were examined at both macro- and micro levels in these plastination sections and the reconstructed 3-dimensional visualization model. RESULTS: The HC was an upward arched bony canal with a dumbbell-shaped lumen. According to the arched trajectory of its bottom wall, the HC could be divided into a medial ascending segment and a lateral descending segment. The thickness of the compact bone in the middle part of the HC was thinner than that at the intracranial and extracranial orifices. In 14 of 43 sides (32.6%), the posterior wall or the roof of the HC were disturbed by passing venous channels which communicated the posterior condylar emissary vein and the inferior petroclival vein. The trajectory of hypoglossal nerve in HC is mainly from anterosuperior to posteroinferior. The meningeal dura and the arachnoid extended into the HC along the hypoglossal nerve to form the dural and arachnoid sleeves and then fused with the nerve near the extracranial orifice of the HC. CONCLUSIONS: Knowledge of the detailed anatomy of the HC can be helpful in avoiding surgical complications when performing surgery for lesions and the occipital condylar screw placement in this complex area.

Association between domain-specific sedentary behaviour and endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Sedentary behaviour is associated with increased cancer risk. We aim to assess the associations of domain-specific and total sedentary behaviour with risk of endometrial cancer, with additional attention paid to potential differences in adjustment strategy for obesity and physical activity. DESIGN: A systematic review and meta-analysis was conducted in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews (PRISMA) and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). DATA SOURCES: PubMed, Embase and MEDLINE databases were searched up to 28 February 2023, supplemented by grey literature searches. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational human studies evaluating the association between sedentary behaviour and endometrial cancer. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and conducted the quality assessment based on Newcastle-Ottawa Scale (NOS) independently. We used a random-effects model with inverse variance approach to pool the estimates. The extent of heterogeneity was quantified with the I 2 statistics. RESULTS: Sixteen studies were included in the systematic review. Fourteen studies involving 882 686 participants were included in the meta-analysis. The pooled relative risks (RRs) for high versus low level of overall sedentary behaviour was 1.28 (95% CI: 1.14 to 1.43; I2 =34.8%). The increased risk regarding specific domains was 1.22 (95% CI: 1.09 to 1.37; I2=13.4%, n=10) for occupational domain, 1.34 (95% CI: 0.98 to 1.83; I2=53.7%, n=6) for leisure-time domain and 1.55 (95% CI: 1.27 to 1.89; I2=0.0%, n=2) for total sedentary behaviour. Larger pooled RRs were observed among studies with adjustment for physical activity and studies without adjustment for body mass index. CONCLUSIONS: Higher levels of sedentary behaviour, total and occupational sedentary behaviour in particular, increase the risk of endometrial cancer. Future studies are needed to verify domain-specific associations based on objective quantification of sedentary behaviour, as well as the interaction of physical activity, adiposity and sedentary time on endometrial cancer.

A Model to Identify Candidates for Lymph Node Dissection Among Patients With High-Risk Endometrial Endometrioid Carcinoma According to Mayo Criteria.

Background: The Mayo criteria are the most widely accepted algorithm for predicting the risk of lymph node metastasis in endometrial endometrioid carcinoma (EEC). However, the clinical value of these criteria in high-risk patients is limited and inconclusive. Methods: A total of 240 patients with EEC meeting the Mayo high-risk criteria between January 1, 2015, and December 31, 2018 were included in our study. We retrospectively collected the laboratory reports, basic clinical information, clinicopathological and immunohistochemistry (IHC) findings, and the sequences of molecular pathological markers of these patients. A nomogram for predicting the likelihood of positive lymph node status was established based on these parameters. Results: Among the 240 patients, 17 were diagnosed with lymph node metastasis. The univariable analyses identified myometrial invasion >50%, aberrant p53 expression, microsatellite instable (MSI), and cancer antigen 125 (CA125) ≥35 U/ml as potential risk factors for lymph node metastasis. The multivariable analyses showed that aberrant p53 expression, MSI, and CA125 ≥35 U/ml were independent predictors of lymph node metastasis. The area under the curve (AUC) for the nomogram was 0.870, as compared to 0.665 for the Mayo criteria. Conclusions: Our novel prediction model effectively identifies patients at high risk for lymphatic metastasis. This model is a promising strategy for personalized surgery in patients with high risk according to the Mayo criteria.

Ambient air pollution on fecundity and live birth in women undergoing assisted reproductive technology in the Yangtze River Delta of China.

BACKGROUND: Ambient air pollution has adverse effects on the reproductive system. However, inconsistent conclusions were reached from different studies with regard to air pollutants and pregnancy outcomes, especially the livebirth rate in assisted reproductive technology (ART) in different windows of exposure. METHODS: A retrospective cohort study was conducted on 12,665 women who underwent first fresh or frozen embryo transfer cycle in the Yangtze River Delta of China. Daily average levels of six air pollutants in four different periods were obtained: Period 1 and 2: 90 days or one year prior to oocyte retrieval; Period 3 and 4: the day of oocyte retrieval or one year prior to oocyte retrieval to the day of serum hCG test or to the end of the pregnancy. A multiple logistic regression model was used to investigate the association between air pollutant exposure and pregnancy outcomes. Stratified analyses were conducted to explore potential modifier effects. RESULTS: The one year exposure window (Period 2) before oocyte retrieval had a more evident negative association with pregnancy outcomes. Each IQR increase in ambient PM10 (OR: 0.89, 95% CI: 0.84-0.93), PM2.5 (OR: 0.82, 95% CI: 0.77-0.87), SO2 (OR: 0.87, 95% CI: 0.83-0.91) and CO (OR: 0.91, 95% CI: 0.87-0.96) was associated with a respective 11%, 18%, 13% and 9% decrease in the likelihood of live birth. In entire exposure window of Period 4, all air pollutants except for O3 were associated with a decreased likelihood of live birth. Stratified analyses showed that women undergoing frozen embryo transfer cycles, especially those with two embryos transferred, were more vulnerable to air pollutant exposure. CONCLUSION: This study indicates a negative association between air pollutant exposure before oocyte retrieval and livebirth rate in ART. The adverse impact was more evident in one year exposure compared to three-month refresh cycle of the gametes. Additional protection from air pollution should be undertaken at least one year before ART, particularly for those with frozen embryo transfer cycles.

The association between tobacco smoke exposure and vitamin D levels among US general population, 2001-2014: temporal variation and inequalities in population susceptibility.

Tobacco smoking is endocrine-disrupting and may interfere with vitamin D endocrine systems (VDES), but supporting evidence is limited and inconsistent. Also, there is a lack of evidence on whether the association between tobacco smoke exposure and VD levels exhibit temporal variation. Data from the National Health and Nutrition Examination Survey was used to evaluate the association between tobacco smoke exposure and VD levels among US general participants from 2001 to 2014. We examined the linear association between serum cotinine and 25(OH)D concentrations, as well as relationship between tobacco smoke exposure categories (active, passive, non-smoking) with VD status (deficiency, inadequacy, sufficiency, intoxication), and assessed whether specific gender, age (3-11, 12-19, 20-59, ≥ 60 years), ethnicity/race, or body mass index (BMI) groups were disproportionately impacted. During 2001-2004, a decrease in both serum cotinine and passive smoking prevalence was observed, with a stabilized active smoking rate. The estimates for the association between tobacco smoke exposure and suboptimal VD levels increased over the study period. Overall results indicated that serum cotinine was negatively associated with 25(OH)D in all participants. Tobacco smoke exposure, including both active and passive smoking exposure, was associated with increased risk of VD deficiency. Moreover, active smoking was additionally related to enhanced risk of VD inadequacy. These associations showed some age and gender differences, with consistent and stronger associations observed in female adults. In contrast, effects of tobacco smoke exposure on VD levels were mostly negative or non-significant among children and adolescents aged 3-19 years. The percentage of US general population with active smoking exposure stabilized over the 14-year period and was still high. Tobacco smoke exposure may disrupt vitamin D levels with an increasing temporal trend in the risk. Our results also provided initial evidence of smoking exposure on VD intoxication, which needs to be further verified. Convincing studies have linked tobacco use exposure, to dysfunctional VDES accompanied with declined serum levels of VD metabolites. However, evidence on the association between tobacco smoke exposure and VD status was rather limited and inconsistent, and there were no researches to date that estimated the temporal variation of the association as well as the effects of smoke exposure on VD intoxication. This study analyzed national survey data, to evaluate the temporal trends in effects of tobacco smoke exposure on VD levels over a decade, and to comprehensively assess the impacts of tobacco smoke exposure on VD levels across specific subgroups. The evidence suggests that the prevalence of active smoking exposure stabilized over the 14-year period and was still high. Moreover, tobacco smoke exposure may disrupt vitamin D levels among general population, with an increasing temporal trend and age-, gender-differences in risk.

Overexpression of NEK3 is associated with poor prognosis in patients with gastric cancer.

The NIMA-related kinase 3 (NEK3) plays an important role in cell migration, cell proliferation, and cell viability. Recently, NEK3 was reported to enhance the malignancy of breast cancer. However, its role in gastric cancer has not been completely characterized. In this study, we explored the prognostic significance of NEK3 in human gastric cancer. Reverse transcription-polymerase chain reaction and western blot were performed to detect the NEK3 mRNA and protein expression in 6 paired fresh human gastric cancer tissues and surrounding normal tissues. NEK3 levels in gastric cancer and its adjacent normal samples of 168 cases were detected by immunohistochemistry, and the relationships between the NEK3 level and various clinicopathological features were analyzed. NEK3 mRNA and protein were significantly overexpressed in gastric cancer tissues, compared with adjacent normal tissues. Immunohistochemistry staining assay showed the percentage of high NEK3 expression in gastric cancer samples was higher than that in adjacent normal samples. NEK3 overexpression was significantly correlated with pT stage, pathologic TNM stage, lymph node metastasis, and poor prognosis of gastric cancer. Cox multivariate regression analyses suggested that NEK3 was an independent prognostic factor for survival of patients with gastric cancer. The data demonstrate that NEK3 is overexpressed in gastric cancer, which promotes the malignancy of gastric cancer. NEK3 may be as a prognostic biomarker and a potential therapeutic target for gastric cancer.