Comparison of the perinatal outcomes of expected high ovarian response patients and normal ovarian response patients undergoing frozen-thawed embryo transfer in natural/small amount of HMG induced ovulation cycles.

BACKGROUND: Due to the high risk of complications in fresh transfer cycles among expected high ovarian response patients, most choose frozen-thawed embryo transfer (FET). There are currently few researches on whether the FET outcomes of expected high ovarian response patients with regular menstrual cycles are similar to those of normal ovarian response. Therefore, our objective was to explore and compare pregnancy outcomes and maternal and neonatal outcomes of natural FET cycles between patients with expected high ovarian response and normal ovarian response with regular menstrual cycles based on the antral follicle count (AFC). METHODS: This retrospective cohort study included 5082 women undergoing natural or small amount of HMG induced ovulation FET cycles at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2017, to March 31, 2021. The population was divided into expected high ovarian response group and normal ovarian response group based on the AFC, and the differences in patient characteristics, clinical outcomes and perinatal outcomes between the two groups were compared. RESULTS: Regarding clinical outcomes, compared with the normal ovarian response group, patients in the expected high ovarian response group had a higher clinical pregnancy rate (57.34% vs. 48.50%) and live birth rate (48.12% vs. 38.97%). There was no difference in the early miscarriage rate or twin pregnancy rate between the groups. Multivariate logistic regression analysis suggested that the clinical pregnancy rate (adjusted OR 1.190) and live birth rate (adjusted OR 1.171) of the expected high ovarian response group were higher than those of the normal ovarian response group. In terms of maternal and infant outcomes, the incidence of very preterm delivery in the normal ovarian response group was higher than that in the expected high ovarian response group (0.86% vs. 0.16%, adjusted OR 0.131), Other maternal and infant outcomes were not significantly different. After grouping by age (< 30 y, 30-34 y, 35-39 y), there was no difference in the incidence of very preterm delivery among the age subgroups. CONCLUSION: For patients with expected high ovarian response and regular menstrual cycles undergoing natural or small amount of HMG induced ovulation FET cycles, the clinical and perinatal outcomes are reassuring. For patients undergoing natural or small amount of HMG induced ovulation FET cycles, as age increases, perinatal care should be strengthened during pregnancy to reduce the incidence of very preterm delivery.

Shaping the future of chronic disease management: Insights into patient needs for AI-based homecare systems.

BACKGROUND: The rising demand for healthcare resources, especially in chronic disease management, has elevated the importance of Artificial Intelligence (AI) in healthcare. While AI-based homecare systems are being developed, the perspectives of chronic patients, who are one of the primary beneficiaries and risk bearers of these technologies, remain largely under-researched. While recent research has highlighted the importance of AI-based homecare systems, the current understanding of patients' desired designs and features is still limited. OBJECTIVE: This paper explores chronic patients' perspectives regarding AI-based homecare systems, an area currently underrepresented in research. We aim to identify the factors influencing their decision to use such systems, elucidate the potential roles of government and other concerned authorities, and provide feedback to AI developers to enhance adoption, system design, and usability and improve the overall healthcare experiences of chronic patients. METHOD: A web-based open-ended questionnaire was designed to gather the perspectives of chronic patients about AI-based homecare systems. In total, responses from 181 participants were collected. Using Krippendorff's clustering technique, an inductive thematic analysis was performed to identify the main themes and their respective subthemes. RESULT: Through rigorous coding and thematic analysis of the collected responses, we identified four major themes further segmented into thirteen subthemes. These four primary themes were: 1) "Personalized Design", emphasizing the need for patients to manage their health condition better through personalized and educational resources and user-friendly interfaces; 2) "Emotional & Social Support", underscoring the desire for AI systems to facilitate social connectivity and provide emotional support to improve the well-being of chronic patients at home; 3) "System Integration & Proactive Care", addressing the importance of seamless communication, proactive patient monitoring and integration with existing healthcare platforms; and 4) "Ethics & Regulation", prioritizing ethical guidelines, regulatory compliance, and affordability in the design. CONCLUSION: This study has offered significant insights into the needs and expectations of chronic patients regarding AI-based home care systems. 'The findings highlight the importance of personalized and accessible care, emotional and social support, seamless system integration, proactive care, and ethical considerations in designing and implementing such systems. By aligning the design and operation of these systems with the lived experiences and expectations of patients, we can better ensure their acceptance and effectiveness.

Perspectives of Patients With Chronic Diseases on Future Acceptance of AI-Based Home Care Systems: Cross-Sectional Web-Based Survey Study.

BACKGROUND: Artificial intelligence (AI)-based home care systems and devices are being gradually integrated into health care delivery to benefit patients with chronic diseases. However, existing research mainly focuses on the technical and clinical aspects of AI application, with an insufficient investigation of patients' motivation and intention to adopt such systems. OBJECTIVE: This study aimed to examine the factors that affect the motivation of patients with chronic diseases to adopt AI-based home care systems and provide empirical evidence for the proposed research hypotheses. METHODS: We conducted a cross-sectional web-based survey with 222 patients with chronic diseases based on a hypothetical scenario. RESULTS: The results indicated that patients have an overall positive perception of AI-based home care systems. Their attitudes toward the technology, perceived usefulness, and comfortability were found to be significant factors encouraging adoption, with a clear understanding of accountability being a particularly influential factor in shaping patients' attitudes toward their motivation to use these systems. However, privacy concerns persist as an indirect factor, affecting the perceived usefulness and comfortability, hence influencing patients' attitudes. CONCLUSIONS: This study is one of the first to examine the motivation of patients with chronic diseases to adopt AI-based home care systems, offering practical insights for policy makers, care or technology providers, and patients. This understanding can facilitate effective policy formulation, product design, and informed patient decision-making, potentially improving the overall health status of patients with chronic diseases.

Early language exposure affects neural mechanisms of semantic representations.

One signature of the human brain is its ability to derive knowledge from language inputs, in addition to nonlinguistic sensory channels such as vision and touch. How does human language experience modulate the mechanism by which semantic knowledge is stored in the human brain? We investigated this question using a unique human model with varying amounts and qualities of early language exposure: early deaf adults who were born to hearing parents and had reduced early exposure and delayed acquisition of any natural human language (speech or sign), with early deaf adults who acquired sign language from birth as the control group that matches on nonlinguistic sensory experiences. Neural responses in a semantic judgment task with 90 written words that were familiar to both groups were measured using fMRI. The deaf group with reduced early language exposure, compared with the deaf control group, showed reduced semantic sensitivity, in both multivariate pattern (semantic structure encoding) and univariate (abstractness effect) analyses, in the left dorsal anterior temporal lobe (dATL). These results provide positive, causal evidence that language experience drives the neural semantic representation in the dATL, highlighting the roles of language in forming human neural semantic structures beyond nonverbal sensory experiences.

Humans are the only known species where much of knowledge learning happens symbolically through language, in addition to information received directly from the senses. For example, humans can learn about the color of some rose flowers from the popular expression "roses are red" without needing to see any red roses ­ allowing them to accumulate knowledge beyond the constraints of their own senses. Recent work suggests that a region of the brain known as the dorsal anterior temporal lobe represents knowledge acquired from language instead of sensory experiences. However, these studies were based on volunteers deprived of sensory experiences rather than those with reduced language exposure. Therefore, it was not clear whether this brain structure represents knowledge derived specifically from language and the importance of language in shaping non-sensory knowledge. To address this question, Wang et al. studied the brain activity of deaf adult volunteers in a word meaning judgement task. Volunteers were either born deaf or lost their hearing as toddlers, and all primarily used Chinese Sign Language for communication. One group of volunteers had been exposed to sign language from birth, giving them similar exposure to language as hearing individuals. The other group had less exposure to language in their early years and only learned sign language later in childhood. The task included 90 written words that were familiar to the volunteers. They included a mixture of object words ­ related to material objects ­ such as "shoulder" and "hammer" and abstract words ­ which are not linked to physical objects ­ such as "cause" and "violence". The volunteers were shown each word in turn and asked to think about the word's meaning. Brain scans revealed that the left dorsal anterior temporal lobes of the volunteers with reduced early language exposure were less sensitive to the meaning of the words compared with those of the other volunteers. The findings demonstrate that the dorsal anterior temporal lobe specifically supports meaning derived from a person's experience of language as opposed to sensory experience, providing a new angle to understand the mechanism of knowledge representations. Increased understanding of how language supports knowledge will help to uncover the human-specific ways of representing and creating knowledge in the brain.

A visualized MAC nomogram online predicts the risk of three-month mortality in Chinese elderly aneurysmal subarachnoid hemorrhage patients undergoing endovascular coiling.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is an aggressive disease with higher mortality rate in the elderly population. Unfortunately, the previous models for predicting clinical prognosis are still not accurate enough. Therefore, we aimed to construct and validate a visualized nomogram model to predict online the 3-month mortality in elderly aSAH patients undergoing endovascular coiling. METHOD: We conducted a retrospective analysis of 209 elderly aSAH patients at People's Hospital of Hunan Province, China. A nomogram was developed based on multivariate logistic regression and forward stepwise regression analysis, then validated using the bootstrap validation method (n = 1000). In addition, the performance of the nomogram was evaluated by various indicators to prove its clinical value. RESULT: Morbid pupillary reflex, age, and using a breathing machine were independent predictors of 3-month mortality. The AUC of the nomogram was 0.901 (95% CI: 0.853-0.950), and the Hosmer-Lemeshow goodness-of-fit test showed good calibration of the nomogram (p = 0.4328). Besides, the bootstrap validation method internally validated the nomogram with an area under the curve of the receiver operator characteristic (AUROC) of 0.896 (95% CI: 0.846-0.945). Decision curve analysis (DCA) and clinical impact curve (CIC) indicated the nomogram's excellent clinical utility and applicability. CONCLUSION: An easily applied visualized nomogram model named MAC (morbid pupillary reflex-age-breathing machine) based on three accessible factors has been successfully developed. The MAC nomogram is an accurate and complementary tool to support individualized decision-making and emphasizes that patients with higher risk of mortality may require closer monitoring. Furthermore, a web-based online version of the risk calculator would greatly contribute to the spread of the model in this field.

The role of noncoding RNAs in cancer lipid metabolism.

Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.

Optimal waiting period for frozen embryo transfer after hysteroscopic polypectomy: A propensity score matching analysis.

Objective: To evaluate the optimal waiting period for frozen-thawed embryo transfer (FET) after hysteroscopic polypectomy (HSC-P). Design: Retrospective cohort. Setting: University-affiliated hospital. Patients: All patients included in this research underwent hysteroscopy before the first FET cycle after whole embryo freezing. A total of 206 patients had undergone HSC-P, and 3681 patients without endometrial polyps were defined as the controls. Interventions: HSC-P. Main outcome measures: The HSC-P group was divided into three subgroups based on the time interval between HSC-P and the start of an FET cycle. Subgroup 1 consisted of patients who underwent FET after their next menses, subgroup 2 after two menstrual cycles, and subgroup 3 after three or more menstrual cycles. Demographics, baseline in vitro fertilization (IVF) characteristics, and pregnancy outcomes, especially perinatal outcomes after FET were compared among the groups. Results: There were 137 patients in subgroup 1, 40 in subgroup 2, and 29 in subgroup 3. There were no differences in the baseline characteristics of the three groups. IVF-related data and FET-related data, such as endometrial thickness and ET no. Of embryoes, were similar among the three subgroups. The three subgroups showed no significant differences in implantation rate, biochemical pregnancy rate, abortion rate, clinical pregnancy rate or live birth rate. Besides, There was no significant difference in perinatal outcomes including very preterm delivery, preterm delivery, low birth weight, macrosomia, small for gestational age, large for gestational age, birth weight(g), birth-height(cm)and Apgar Scores. Conclusions: Compared with FET after their next menses, FET after two or more menstrual cycles after HSC-P does not necessarily produce superior outcomes.

An Alternatively Spliced p62 Isoform Confers Resistance to Chemotherapy in Breast Cancer.

Resistance to chemotherapy remains a major obstacle to the successful treatment of breast cancer. More than 80% of patients who receive neoadjuvant chemotherapy (NAC) do not achieve a pathologic complete response. In this study, we report a novel p62 mRNA isoform with a short 3'-UTR (untranslated region; p62-SU, 662-nt) that is associated with chemoresistance in breast cancer cells and tissue specimens. The p62 mRNA isoform was identified by RNA sequencing with qRT-PCR, 3'-RACE, and Northern blot analysis. In vitro and in vivo, ectopic expression of p62-SU promoted breast cancer cell proliferation, migration, invasion, and chemoresistance compared with the p62 mRNA isoform with a full-length 3'-UTR (p62-LU, 1,485-nt). Mechanistically, cleavage and polyadenylation specific factor 1 (CPSF1) modulated the 3'-UTR of p62 through alternative polyadenylation. In addition, p62-SU escaped miR-124-3p-mediated repression and upregulated p62-SU protein expression, thereby inducing p62-dependent chemoresistance. These data suggest that a CPSF1-p62-miR-124-3p signaling axis is responsible for reduced sensitivity of breast cancer to chemotherapy. SIGNIFICANCE: Resistance to NAC in breast cancer is driven by a novel p62 mRNA isoform that escapes miRNA-mediated repression and leads to increased p62 protein expression.

Risk subtyping and prognostic assessment of prostate cancer based on consensus genes.

Prostate cancer (PCa) is the most frequent malignancy in male urogenital system around worldwide. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assays were used to assess the biological functions of key genes. Thirty-nine intersecting consensus prognostic genes from five independent cohorts were identified. Subsequently, an eleven-consensus-gene classifier was established. In addition, multivariate Cox regression analyses showed that the classifier served as an independent indicator of recurrence-free survival in three of the five cohorts. Combined receiver operating characteristic (ROC) analysis achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits cell proliferation, while ITGA11 promotes cell migration and invasion, possibly through the PI3K/AKT signaling pathway. To conclude, we established and validated an eleven-consensus-gene classifier, which may add prognostic value to the currently available staging system.

Aryl acrylonitriles synthesis enabled by palladium-catalyzed α-alkenylation of arylacetonitriles with vinyl halides/triflates.

Aryl acrylonitriles are an important subclass of acrylonitriles in the medicinal chemistry and pharmaceutical industry. Herein, an efficient synthesis of aryl acrylonitrile derivatives using a Palladium/NIXANTPHOS-based catalyst system was developed. This approach furnishes a variety of substituted and functionalized aryl acrylonitriles (up to 95% yield). The scalability of the transformation and the synthetic versatility of aryl acrylonitrile were demonstrated.

Social and emotion dimensional organizations in the abstract semantic space: the neuropsychological evidence.

An essential aspect of human cognition is supported by a rich reservoir of abstract concepts without tangible external referents (e.g., "honor", "relationship", "direction"). While decades of research showed that the neural organization of conceptual knowledge referring to concrete words respects domains of evolutionary salience and sensorimotor attributes, the organization principles of abstract word meanings are poorly understood. Here, we provide neuropsychological evidence for a domain (sociality) and attribute (emotion) structure in abstract word processing. Testing 34 brain-damaged patients on a word-semantic judgment task, we observed double dissociations between social and nonsocial words and a single dissociation of sparing of emotional (relative to non-emotional) words. The lesion profiles of patients with specific dissociations suggest potential neural correlates positively or negatively associated with each dimension. These results unravel a general domain-attribute architecture of word meanings and highlight the roles of the social domain and the emotional attribute in the non-object semantic space.

sRAGE downregulates the VEGF expression in OHSS ovarian granulosa cells.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is mainly caused by human chorionic gonadotropin (hCG) through vasoactive mediators such as vascular endothelial growth factor (VEGF) and various inflammatory factors. Our previous study showed that soluble receptor for advanced glycation end products (sRAGE) played a protective role in PCOS by inhibiting VEGF, so wanted to explore the role of sRAGE in OHSS. METHODS: Two sets of experiments were performed in this study. In part one, sRAGE protein levels in follicular fluid (FF) samples from 60 patients with OHSS and 60 non-OHSS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 25 patients with OHSS and cultured. Then, ovarian granulosa cells were treated with different concentrations of sRAGE. Granulosa cells cultured without sRAGE stimulation were used as the control group. The levels of VEGF, amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG) mRNA were examined by quantitative RT-PCR. The protein levels of VEGF, AREG, BTC, and EREG were measured by ELISA. RESULTS: Compared with non-OHSS patients, patients with OHSS exhibited lower sRAGE levels in both serum and FF (p < .05). Treatment with sRAGE decreased the production of VEGF, and the effects were dependent on the concentration of sRAGE (p < .05). Simultaneously, the expression of the EGF-like growth factors AREG, BTC and EREG was decreased, and their expression was dependent on the concentration of sRAGE (p < .05). CONCLUSIONS: sRAGE downregulate VEGF expression in OHSS ovarian granulosa cells, in which EGF-like growth factor pathway may be involved, and sRAGE may play a potential protective role in OHSS.

Integrated Analysis Revealed the MicroRNA-Based Prognostic Predicting Signature for Papillary Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is one of the most frequently occurring tumors worldwide. Herein, we established a microRNA (miRNA) predicting signature to assess the prognosis of papillary-type RCC (PRCC) patients. miR-1293, miR-34a, miR-551b, miR-937, miR-299, and miR-3199-2 were used in building the overall survival (OS)-related signature, whereas miR-7156, miR-211, and miR-301b were used to construct the formula of recurrence-free survival (RFS) with the help of LASSO Cox regression analysis. The Kaplan-Meier and receiver operating characteristic curves indicated good discrimination and efficiency of the two signatures. Functional annotation for the downstream genes of the OS/RFS-related miRNAs exposed the potential mechanisms of PRCC. Notably, the multivariate analyses suggested that the two signatures were independent risk factors for PRCC patients and had better prognostic capacity than any other classifier. In addition, the nomogram indicated synthesis effects and showed better predictive performance than clinicopathologic features and our signatures. We validated the OS and RFS prediction formulas in clinical samples and met our expectations. Finally, we established two novel miRNA-based OS and RFS predicting signatures for PRCC, which are reliable tools for assessing the prognosis of PRCC patients.

Predicted the P2RX7 rs3751143 polymorphism is associated with cancer risk: a meta-analysis and systematic review.

BACKGROUND: Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism and the risk of cancer. MATERIALS AND METHODS: The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel-Haenszel) or random-effects (DerSimonian-Laird) models were selected to summarise the collective effects. RESULTS: Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models. CONCLUSIONS: Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.

PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E.

It is commonly accepted that cellular protein levels are primarily determined by mRNA levels. However, discordance between protein and mRNA expression has been implicated in many pathologic conditions including oncogenesis. The mechanisms involved in this discordance are complicated and far from understood. In this study, it was observed that the expression levels of poly(C) binding protein 2 (PCBP2) mRNA and protein were diametric in breast normal and cancer cell lines, paraffin-embedded and fresh tissue specimens, consistent with data from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium. Moreover, PCBP2 protein expression was significantly associated with disease progression and poor outcome in patients with breast cancer. Depletion of PCBP2 protein inhibited cell proliferation, colony formation, migration, invasion, and in vivo tumor growth and metastasis. Forced expression of PCBP2 exhibited the opposite effect. Mechanistically, it was demonstrated that PCBP2 3' untranslated region (3'UTR) was subject to alternative splicing and polyadenylation (APA) in breast cancer tissues and cell lines. Non-full-length 3'UTR PCBP2 transcripts yielded more protein than the full-length 3'UTR transcripts and enhanced the oncogenic and metastatic capacities of human breast cancer cells. Furthermore, UFD1 and NT5E were identified as genes downstream of PCBP2. PCBP2 promoted oncogenicity of breast cancer cells via upregulation of the expression of UFD1 and NT5E by direct binding to their 3'UTR-B portions. IMPLICATIONS: Findings demonstrate that APA of PCBP2 3'UTR contributes to its increased expression with subsequent promotion of breast cancer progression by regulating UFD1 and NT5E. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/1/86/F1.large.jpg.

Long-Term Assessment of Rehabilitation Treatment of Sports through Artificial Intelligence Research.

BACKGROUND: Artificial intelligence (AI) technology has been incorporated into all walks of life, especially the integration of machine learning and health management has achieved very significant progress and results. It is very necessary to analyze personalized sports health management services and long-term assessment of health issues in the era of AI. METHODS: This paper explores AI + personalized sports management service system design ideas, system operation process, management stage design, taking common chronic diseases, and diabetes as examples. 150 patients were divided into an observation group and a control group, and the blood glucose, blood pressure, blood lipid, and knowledge awareness rate were compared. RESULTS: The blood glucose, blood pressure, and blood lipid levels of the observation group all reduced, and the awareness rate of diabetes knowledge increased, which proved that the AI research has great value in sports rehabilitation research coupled with long term health assessment and is worth further research. CONCLUSION: The AI research proposed in this paper is of far-reaching practical significance in helping the transformation and upgrading of the sports health management service industry, promoting the innovative development of sports health management service supply, and promoting national fitness and national health.

What Does Unexpected Suboptimal Response During Ovarian Stimulation Suggest, an Overlooked Group?

Unlike poor ovarian response, despite being predicted to be normal responders based on their ovarian reserve markers, many patients respond suboptimally to ovarian stimulation. Although we can improve the number of retrieved oocytes by increasing the recombinant FSH dose and adding LH, the effect of suboptimal ovarian response on cumulative live birth rate (CLBR) and offspring safety is unclear. This study focuses on the unexpected suboptimal response during ovulation induction, and its causes and outcomes are analysed for the first time with a large amount of data used to compare the cumulative pregnancy rate (CPR), CLBR and offspring safety of patients with one complete ART cycle with all embryos used. Our analysis included 5218 patients treated with the GnRH agonist long protocol for their first IVF-embryo transfer (ET) cycles. Patients were divided into two groups according to whether the ovarian response was suboptimal. Propensity score matching (PSM) was utilized for sampling at up to 1:1 nearest-neighbour matching with caliper 0.05 to balance the baseline and improve comparability between the groups. Results showed that age, BMI and basal FSH were independent risk factors for slow response; the initial dosage of Gn, FSH on the first day of Gn, and LH on the first day of Gn were independent protective factors for suboptimal response. Suboptimal responders were also more likely to have irregular menses. Regarding the clinical pregnancy rate of the fresh IVF/ICSI-ET cycles, the adjusted results of the two groups were not significantly different. There was no difference in the CPR, CLBR, or offspring safety-related data, such as gestational age, preterm delivery rate, birthweight, birth-height and Apgar Scores between the two groups after PSM. Age-related changes in the number of oocytes retrieved from women aged 20-40 years old between the two groups were different, indicating that suboptimal response in elderly patients suggests a decline in ovarian reserve. Although we can now improve the outcomes of suboptimal responders, it increases the cost to the patients and the time to live birth, which requires further attention.

NUDT21 Suppresses Breast Cancer Tumorigenesis Through Regulating CPSF6 Expression.

BACKGROUND: NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. PURPOSE: The aim of this study was to investigate the clinical significance and functional role of NUDT21 in breast cancer. METHODS: The protein expression of NUDT21 was examined by immunohistochemistry (IHC) in 100 paraffin-embedded, archived breast cancer samples and 100 benign breast tissues. Then, the correlations between the NUDT21 expression and clinicopathologic characteristics and prognoses of the breast cancer patients were analyzed. In addition, the function of NUDT21 in breast cancer cell lines was detected by the methyl thiazolyl tetrazolium, colony formation and transwell assays. Finally, mass spectrometry analysis and Western blotting were used to identify the proteins that interact directly with NUDT21. RESULTS: IHC analysis revealed that the expression of NUDT21 was significantly lower in breast cancer tissues compared with benign breast disease tissues. The correlation analysis revealed that low expression of NUDT21 was positively correlated with tumor size, lymph node metastasis, and TNM stage. Also, Kaplan-Meier survival curves showed that patients with lower NUDT21 expression had shorter overall survival and relapse-free survival compared with higher NUDT21 expression. In addition, the knockdown of NUDT21 enhanced cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Consistently, the overexpression of NUDT21 inhibited cell proliferation, migration, invasion, and EMT. In addition, NUDT21 directly interacted with CPSF6 and negatively regulated its expression. Moreover, the knockdown of CPSF6 reversed NUDT21 expression-induced cancer cell migration and invasion. CONCLUSION: NUDT21 might play a tumor-suppressive role by inhibiting cell proliferation and invasion via the NUDT21/CPSF6 signaling pathway in breast cancer cells.

Systematic investigation of biomarker-like role of ARHGDIB in breast cancer.

BACKGROUND: ARHGDIB, a Rho GDP dissociation inhibitor protein, has been reported playing critical roles in regulation of multiple biological responses. However, whether ARHGDIB serves as a valuable biomarker in cancer is little known so far, especially in breast cancer. OBJECTIVE: In this study, we aimed to investigate the importance of ARHGDIB in breast cancer, including but not limited to biomarker-like role, as well as potential mechanisms. METHODS: Total 100 breast cancer samples and 100 benign breast disease samples were enrolled and underwent detailed pathological assessment and IHC analysis. Human breast cancer cell lines and epithelial cell line were subjected to siRNA-mediated knock-down, RT-qPCR, western blot, MTT staining, cell cycle assay, transwell analysis respectively. RESULTS: We observed the expression of ARHGDIB is significantly higher in human breast cancer tissues compared with the benign tissues. ARHGDIB expression was positively correlated with tumor size, lymph node metastasis and TNM stage in breast cancer patients. Moreover, ARHGDIB depletion decreased proliferation, migration and invasion of breast cancer cells. Furthermore, we found ARHGDIB mediated epithelial-mesenchymal transition, and MMP2 is the key downstream effector of ARHGDIB. CONCLUSIONS: Hence, our results suggested the significance and predictive role of ARHGDIB in breast cancer. High expression of ARHGDIB indicated the poor prognosis for breast cancer patients.