Association between educational attainment and thyroid cancer: evidence from a univariable and multivariable Mendelian randomization study.

BACKGROUND: Thyroid cancer and educational attainment have been related in observational studies. It is unclear if these correlations indicate causative relationships. METHODS: Using large-scale genome-wide association studies (GWAS) datasets, we conducted an univariable and multivariable Mendelian randomization (MR) study to assess a potential connection between educational attainment and thyroid cancer. The inverse-variance weighted (IVW) analysis method is used as our primary outcome. Additionally, we carry out several sensitivity analyses to evaluate the pleiotropy and robustness of the causal estimates. RESULTS: Univariate MR study shows 4.2 years of additional education is associated with a 41.4% reduction in thyroid cancer risk (OR = 0.586; 95% CI: 0.378-0.909; P = 0.017). Further multivariable MR analysis revealed that body mass index (BMI) acted as a partial mediating factor in the protective impact of higher educational attainment against thyroid cancer. CONCLUSION: This MR study provided genetic evidence that longer education attainment is related to a lower risk of thyroid cancer. Strategies of expanding education may reduce the burden of thyroid cancer in the world.

Bioorthogonal Cu Single-atom Nanozyme for Synergistic Nanocatalytic Therapy, Photothermal Therapy, Cuproptosis, and Immunotherapy.

Single-atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in-depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis of sputtered SAzymes by in situ bombarding-embedding technique. Using this method, sputtered copper (Cu) SAzymes (CuSA) is developed with unreported unique planar Cu-C3 coordinated configuration. To enhance the tumor-specific targeting, we employ a bioorthogonal approach to engineer CuSA, denoted as CuSACO. CuSACO not only exhibits minimal off-target toxicity but also possesses exceptional ultrahigh catalase-, oxidase-, peroxidase-like multienzyme activities, resulting in reactive oxygen species (ROS) storm generation for effective tumor destruction. Surprisingly, CuSACO can release Cu ions in the presence of glutathione (GSH) to induce cuproptosis, enhancing the tumor treatment efficacy. Notably, CuSACO's remarkable photothermal properties enables precise photothermal therapy (PTT) on tumors. This, combined with nanoenzyme catalytic activities, cuproptosis and immunotherapy, efficiently inhibiting the growth of orthotopic breast tumors and gliomas, and lung metastasis. Our research highlights the potential of CuSACO as an innovative strategy to utilize multiple mechanism to enhance tumor therapeutic efficacy, broadening the exploration and development of enzyme-like behavior and physiological mechanism of action of SAzymes.

NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas.

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

Association of major depression, schizophrenia and bipolar disorder with thyroid cancer: a bidirectional two-sample mendelian randomized study.

BACKGROUND: Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer. METHODS: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR-Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs. RESULTS: We used two-sample bidirectional MR analysis to determine whether there was a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI = 1.177-13.299; P = 0.026) and the WME method (OR = 5.563 95% CI = 0.998-31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer. Additionally, our study revealed a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI = 1.123-2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI = 1.014-2.521; P = 0.043) also suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality. CONCLUSIONS: This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate the biological mechanisms of these associations and potential confounders.

The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.

Background: The effect of micronutrients on thyroid cancer has been studied in observational studies, however, the cause of relationships has not yet been determined. Thyroid cancer was the subject of a Mendelian randomization (MR) analysis of micronutrients. Aimed to determine whether micronutrient intake has a causal impact on the chance of developing thyroid cancer. Methods: We used a Mendelian randomization (MR) analysis with two samples. Our circulation levels of Cu, Ir, Zn, Ca, VD, and VC were reflected by genetic variations reported from GWAS in individuals of European ancestry. For the GWAS outcome of thyroid cancer. Sensitivity studies that included MR-Egger, weighted median/mode tests, and a more open selection of variations at a genome-wide sub-significant threshold were added to our inverse-variance weighted (IVW) MR study. Results: Using the IVW approach, we did not find evidence that any of the micronutrients to thyroid cancer (Cu: odds ratio [OR = 0.88, p = 0.41]; Zn: odds ratio [OR = 0.87, p = 0.40]; Ir: odds ratio [OR = 1.18, p = 0.39]; Ca: odds ratio [OR = 1.12, p = 0.43]; VC: odds ratio [OR = 0.95, p = 0.22]; VD: odds ratio [OR = 0.89, p = 0.04]). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. Conclusion: This study does not provide evidence that supplementation with micronutrients including Cu, Ir, Zn, Ca, VD, and VC can prevent thyroid cancer.

MicroRNA-299-3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor-A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC. METHODS: VEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR-299-3p by real-time PCR, western blotting, ELISA and dual-luciferase reporter assays using two UTUC cell lines. The role of miR-299-3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro. RESULTS: High VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer-related death and correlated with poor progression-free and cancer-specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR-299-3p significantly reduced VEGFA protein expression and miR-299-3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3'-UTR. Functional studies indicated that VEGFA overexpression reversed the miR-299-3p-mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR-299-3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2. CONCLUSIONS: Our findings suggest that miR-299-3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR-299-3p could be potential therapeutic targets for UTUC.

Clinical Presentation and Genetic Analysis of Neonatal 11ß-Hydroxylase Deficiency Induced by a Chimeric CYP11B2/CYP11B1 Gene.

In terms of prevalence, 11ß-hydroxylase deficiency (11ß-OHD), a common form of congenital adrenal hyperplasia, closely follows 21-hydroxylase deficiency. 11ß-OHD has been attributed to diminished enzymatic activity owing to CYP11B1 gene variants, mainly encompassing single nucleotide variations and insertions-deletions. The involvement of chimeric CYP11B2/CYP11B1 genes in 11ß-OHD has been rarely reported. We conducted a genetic investigation on a male infant with generalized pigmentation and abnormal steroid hormone levels. Whole-exome sequencing revealed a heterozygous variant in CYP11B1 inherited from the mother (NM_000497.4: c.1391_1393dup [p.Leu464dup]). Long-range polymerase chain reaction revealed an additional allele, a chimeric CYP11B2/CYP11B1 gene, inherited from the father. The current case report emphasizes the need to consider the occurrence of gene fusion variants in the diagnosis of neonatal or early infantile 11ß-OHD.

Risk factors of incontinence-associated dermatitis in older adults: a protocol for systematic review and meta-analysis.

INTRODUCTION: Due to their ageing skin, older adults are more likely to develop incontinence-associated dermatitis (IAD). Although previous attempts to look at the risk factors for IAD in older adults were done, methodological barriers hindered an in-depth understanding. By investigating risk factors for IAD in the ageing population, the development of precise clinical interventions and guidance could be facilitated, which in turn would enhance patient care standards for incontinence management in this target group. To address this knowledge gap, this systematic review with meta-analysis aims to explore the major risk elements linked to IAD among older adults. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols are adhered to in this systematic review and meta-analysis. To achieve its objectives, a comprehensive search strategy PubMed, Embase, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Medline, Chinese Scientific Journal Database (VIP database), WanFang Data Knowledge Service Platform, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, along with other relevant sources published until 18 July 2023 in both English and Chinese languages will be performed. The screening of articles, data abstraction and risk of bias evaluation will be done by two impartial reviewers. RevMan V.5.3 software will be used for data synthesis. The quality of the included study will be assessed using the Newcastle-Ottawa Quality Assessment tool and the Agency for Healthcare Research and Quality. The I 2 test will identify the heterogeneity. ETHICS AND DISSEMINATION: There is no need for ethical approval. Individual patient information or the rights of participants will not be compromised by this protocol. The findings will either be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023442585.

Single-cell analysis reveals exosome-associated biomarkers for prognostic prediction and immunotherapy in lung adenocarcinoma.

BACKGROUND: Exosomes play a crucial role in tumor initiation and progression, yet the precise involvement of exosome-related genes (ERGs) in lung adenocarcinoma (LUAD) remains unclear. METHODS: We conducted a comprehensive investigation of ERGs within the tumor microenvironment (TME) of LUAD using single-cell RNA sequencing (scRNA-seq) analysis. Multiple scoring methods were employed to assess exosome activity (EA). Differences in cell communication were examined between high and low EA groups, utilizing the "CellChat" R package. Subsequently, we leveraged multiple bulk RNA-seq datasets to develop and validate exosome-associated signatures (EAS), enabling a multifaceted exploration of prognosis and immunotherapy outcomes between high- and low-risk groups. RESULTS: In the LUAD TME, epithelial cells demonstrated the highest EA, with even more elevated levels observed in advanced LUAD epithelial cells. The high-EA group exhibited enhanced intercellular interactions. EAS were established through the analysis of multiple bulk RNA-seq datasets. Patients in the high-risk group exhibited poorer overall survival (OS), reduced immune infiltration, and decreased expression of immune checkpoint genes. Finally, we experimentally validated the high expression of SEC61G in LUAD cell lines and demonstrated that knockdown of SEC61G reduced the proliferative capacity of LUAD cells using colony formation assays. CONCLUSION: The integration of single-cell and bulk RNA-seq analyses culminated in the development of the profound and significant EAS, which imparts invaluable insights for the clinical diagnosis and therapeutic management of LUAD patients.

Cigarette smoking and thyroid cancer risk: A Mendelian randomization study.

BACKGROUND: The association between cigarette smoking and thyroid cancer has been reported in prospective cohort studies, but the relationship remains controversial. To investigate this potential correlation further, we employed Mendelian randomization methodology to evaluate the causative impact of smoking on thyroid cancer incidence. METHODS: From the genome-wide association study and Sequencing Consortium of Alcohol and Nicotine use, we obtained genetic variants associated with smoking initiation and cigarettes per day (1.2 million individuals). We also extracted genetic variants associated with past tobacco smoking from the UK Biobank (424,960 individuals). Thyroid cancer outcomes were selected from the FinnGen GWAS (989 thyroid cancer cases and 217,803 control cases). Sensitivity analyses employing various approaches such as weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) have been executed, as well as leave-one-out analysis to identify pleiotropy. RESULTS: Using the IVW approach, we did not find evidence that any of the three smoking phenotypes were related to thyroid cancer (smoking initiation: odds ratio (OR) = 1.56, p = 0.61; cigarettes per day: OR = 0.85, p = 0.51; past tobacco smoking: OR = 0.80, p = 0.78). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. CONCLUSIONS: The MR analysis revealed that there may not exist a causative link between smoking exposure and elevated incidence rates of thyroid malignancies.

Fertility concerns in cancer patients: a bibliometric analysis via CiteSpace: A review.

Fertility concerns are a pervasive issue but very subtle in patients with cancer. Though various studies have focused on fertility concerns, limited research endeavor has been dedicated to bibliometric analysis. Given this, to visually analyze the hot frontier trends of research related to fertility concerns of patients with cancer using CiteSpace and provide new insights for future research in this field using the bibliometric method. We used CiteSpace software to retrieve the literature related to fertility concerns of patients with cancer in the Web of Science core collection database from the year of establishment to 2022 and conducted visual analysis in terms of authors, countries and regions, research institutions, and keywords. The search resulted in 201 valid articles, and the annual publication volume of literature related to fertility concerns in patients with cancer was generally on the rise; the country with the most publications was the United States, which also had the highest influence; the main research institution was Sloan Kettleson Cancer Research Center; the core research scholar was Jessica R. Gorman; the research hotspots mainly centered on quality of survival, women, survivorship, preservation, breast cancer, adolescence, and infertility. The results of this bibliometric study provide the current status and trends in the fertility concerns of patients with cancer and may help researchers identify the hotspots and frontier trends in this field.

Geminal-atom catalysis for cross-coupling.

Single-atom catalysts (SACs) have well-defined active sites, making them of potential interest for organic synthesis1-4. However, the architecture of these mononuclear metal species stabilized on solid supports may not be optimal for catalysing complex molecular transformations owing to restricted spatial environment and electronic quantum states5,6. Here we report a class of heterogeneous geminal-atom catalysts (GACs), which pair single-atom sites in specific coordination and spatial proximity. Regularly separated nitrogen anchoring groups with delocalized π-bonding nature in a polymeric carbon nitride (PCN) host7 permit the coordination of Cu geminal sites with a ground-state separation of about 4 Å at high metal density8. The adaptable coordination of individual Cu sites in GACs enables a cooperative bridge-coupling pathway through dynamic Cu-Cu bonding for diverse C-X (X = C, N, O, S) cross-couplings with a low activation barrier. In situ characterization and quantum-theoretical studies show that such a dynamic process for cross-coupling is triggered by the adsorption of two different reactants at geminal metal sites, rendering homo-coupling unfeasible. These intrinsic advantages of GACs enable the assembly of heterocycles with several coordination sites, sterically congested scaffolds and pharmaceuticals with highly specific and stable activity. Scale-up experiments and translation to continuous flow suggest broad applicability for the manufacturing of fine chemicals.

MicroRNA-145-5p suppresses cell proliferation, migration, and invasion in upper tract urothelial carcinoma by targeting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase.

Upper tract urothelial carcinoma (UTUC), including renal, pelvic, and ureteral carcinoma, has a high incidence rate in Taiwan, which is different from that in Western countries. Therefore, it is imperative to elucidate the mechanisms underlying UTUC growth and metastasis. To explore the function of miR-145-5p in UTUC, we transfected the BFTC909 cell line with miR-145-5p mimics and analyzed the differences in protein levels by performing two-dimensional polyacrylamide gel electrophoresis. Real-time polymerase chain reaction and Western blot analysis were used to analyze 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inositol monophosphate cyclohydrolase (ATIC) messenger RNA and protein levels. A dual-luciferase assay was performed to identify the target of miR-145-5p in ATIC. The effects of miR-145-5p and ATIC expression by cell transfection on cell proliferation, migration, and invasion were also assessed. miR-145-5p downregulated ATIC protein expression. High ATIC expression is associated with tumor stage, metastasis, recurrence, and a poor prognosis in patients with UTUC. Cell function assays revealed that ATIC knockdown inhibited the proliferation, migration, and invasive abilities of UTUC cells. In contrast, miR-145-5p affected the proliferation, migration, and invasive abilities of UTUC cells by directly targeting the 3'-untranslated regions of ATIC. Furthermore, we used RNA sequencing and Ingenuity Pathway Analysis to identify possible downstream genes regulated by ATIC and found that miR-145-5p regulated the protein levels of fibronectin 1, Slug, cyclin A2, cyclin B1, P57, and interferon-induced transmembrane 1 via ATIC. ATIC may be a valuable predictor of prognosis and a potential therapeutic target for UTUC.

Ferromagnetic single-atom spin catalyst for boosting water splitting.

Heterogeneous single-atom spin catalysts combined with magnetic fields provide a powerful means for accelerating chemical reactions with enhanced metal utilization and reaction efficiency. However, designing these catalysts remains challenging due to the need for a high density of atomically dispersed active sites with a short-range quantum spin exchange interaction and long-range ferromagnetic ordering. Here, we devised a scalable hydrothermal approach involving an operando acidic environment for synthesizing various single-atom spin catalysts with widely tunable substitutional magnetic atoms (M1) in a MoS2 host. Among all the M1/MoS2 species, Ni1/MoS2 adopts a distorted tetragonal structure that prompts both ferromagnetic coupling to nearby S atoms as well as adjacent Ni1 sites, resulting in global room-temperature ferromagnetism. Such coupling benefits spin-selective charge transfer in oxygen evolution reactions to produce triplet O2. Furthermore, a mild magnetic field of ~0.5 T enhances the oxygen evolution reaction magnetocurrent by ~2,880% over Ni1/MoS2, leading to excellent activity and stability in both seawater and pure water splitting cells. As supported by operando characterizations and theoretical calculations, a great magnetic-field-enhanced oxygen evolution reaction performance over Ni1/MoS2 is attributed to a field-induced spin alignment and spin density optimization over S active sites arising from field-regulated S(p)-Ni(d) hybridization, which in turn optimizes the adsorption energies for radical intermediates to reduce overall reaction barriers.

Risk factors of incontinence-associated dermatitis among critically ill patients: A systematic review and meta-analysis.

Objectives: Incontinence-associated dermatitis (IAD) is increasingly found among critically ill patients, but the risk factors for IAD in these patients are currently unclear. The purpose of this meta-analysis was to identify the risk factors of IAD in critically ill patients. Methods: Web of Science, PubMed, EMBASE, and Cochrane Library were systemically searched until July 2022. The studies were selected based on inclusion criteria, and data were independently extracted by two researchers. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Odds ratios (ORs) and their associated 95% confidence intervals (CIs) were used to identify significant differences in the risk factors. The I 2 test was used to estimate the heterogeneity of studies, and Egger's test was used to assess the potential publication bias. Results: A total of 7 studies enrolling 1,238 recipients were included in the meta-analysis. Age ≥ 60 (OR = 2.18, 95% CI: 1.38~3.42), female sex (OR = 1.76, 95% CI: 1.32~2.34), dialysis (OR = 2.67, 95% CI: 1.51~4.73), fever (OR = 1.55, 95% CI: 1.03~2.33), vasoactive agent (OR = 2.35, 95% CI: 1.45~3.80), PAT score ≥ 7 (OR = 5.23, 95% CI: 3.15~8.99), frequency of bowel movement > 3times/d (OR = 5.33, 95% CI: 3.19~8.93), and liquid stool (OR = 2.61, 95% CI: 1.56~4.38) were the risk factors of IAD among critically ill patients. Conclusions: Many risk factors are related to IAD among critically ill patients. Nursing staff should pay more attention to evaluating the risk of IAD and enhance the care of high-risk groups.

How does cigarette smoking affect airway remodeling in asthmatics?

Asthma is a prevalent chronic airway inflammatory disease involving multiple cells, and the prolonged course of the disease can cause airway remodeling, resulting in irreversible or partial irreversible airflow limitation and persistent airway hyperresponsiveness (AHR) in asthmatics. Therefore, we must ascertain the factors that affect the occurrence and development of airway remodeling in asthmatics. Smokers are not uncommon in asthmatics. However, there is no systematic description of how smoking promotes airway remodeling in asthmatics. This narrative review summarizes the effects of smoking on airway remodeling in asthmatics, and the progress of the methods for evaluating airway remodeling.

Tunability of the Superconductivity of NbSe2 Films Grown by Two-Step Vapor Deposition.

Layered metallic transition-metal dichalcogenides (TMDCs) are ideal platforms for exploring their fascinating electronic properties at two-dimensional limits, such as their charge density wave (CDW) and superconductivity. Therefore, developing ways to improve the crystallization quality of TMDCs is urgently needed. Here we report superconductively tunable NbSe2 grown by a two-step vapor deposition method. By optimizing the sputtering conditions, superconducting NbSe2 films were prepared from highly crystalline Nb films. The bilayer NbSe2 films showed a superconducting transition temperature that was up to 3.1 K. Similar to the salt-assisted chemical vapor deposition (CVD) method, superconducting monolayer NbSe2 crystals were also grown from a selenide precursor, and the growth strategy is suitable for many other TMDCs. Our growth method not only provides a way to improve the crystalline quality of TMDC films, but also gives new insight into the growth of monolayer TMDCs. It holds promise for exploring two-dimensional TMDCs in fundamental research and device applications.

High MRE11 Expression Level Predicts Poor Survival in Upper Tract Urothelial Carcinomas.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with characteristics of high metastasis and poor prognosis. There are some particularly different features of UTUC between the Asian and Western countries. Double-strand break repair protein MRE11 is a component of the MRN complex that is involved in the DNA repair pathway. Emerging studies have focused on the role of MRE11 in human malignancies with conflicting results. We aimed to establish the relationship between MRE11 expression and the oncological outcome of UTUC. This study retrospectively reviewed 150 patients who underwent radical nephroureterectomy with pathologically confirmed UTUC. Pathologic slides were reviewed, and clinical parameters were collected. An immunohistochemical study was performed, and the cytoplasmic and nuclear-staining results of UTUC were recorded. The expression of MRE11 was analyzed to identify correlations with various clinicopathological parameters, metastasis-free survival, and cancer-specific survival (CSS). MRE11 expression was significantly correlated with patients with a high pathologic stage ( P =0.001), perineural invasion ( P =0.015), and tumor necrosis ( P =0.034). Upon univariate analysis, a high MRE11 expression was associated with poor metastasis-free survival ( P =0.014, 95% CI 1.18, 4.38) and poor CSS ( P =0.001, 95% CI 2.45, 27.75). Upon multivariable analysis, a high MRE11 expression was associated with poor CSS ( P =0.019, 95% CI 1.28, 15.65). In summary, MRE11 expression could serve as a potential predictor of prognosis in patients with UTUC.

Incidence and influencing factors of fertility concerns in breast cancer in young women: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to evaluate the prevalence and influencing factors of fertility concerns in breast cancer in young women. Methods: A literature search on PubMed, Embase, Web of Science, and Cochrane Library databases was conducted up to February 2023 and was analyzed (Revman 5.4 software) in this study. The papers were chosen based on inclusion standards, and two researchers independently extracted the data. The included studies' quality was evaluated using criteria set out by the Agency for Healthcare Research and Quality. To identify significant variations among the risk factors, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were utilized. Results: A total of 7 studies that included 1579 breast cancer in young women were enrolled in the study. The results showed that for breast cancer in young women, the incidence of fertility concerns 53%(95%CI [0.45,0.58]). The results showed that education (2.65, 95% CI 1.65-5.63), full-time work (0.12, 95% CI 1.03-1.93), fertility intentions (7.84, 95% CI 1.50-37.4), depression level (1.25, 95% CI 1.03-1.5), and endocrine therapy (1.32, 95% CI 1.08-1.62) were risk factors for fertility concerns in young women with BC. Having a partner (0.41, 95% CI 0.33-0.5), ≥1 child (0.3, 95% CI 0.22-0.4) were identified as protective factors against fertility concerns in young women with BC. Conclusions: The incidence of fertility concerns in breast cancer in young women is at a moderately high level. We should pay more attention to the risk factors of fertility concerns to help breast cancer in young women cope with their fertility concerns and promote their psychological well-being.