CircUGGT2 facilitates progression and cisplatin resistance of bladder cancer through nonhomologous end-joining pathway.

The development of resistance to cisplatin (CDDP) in bladder cancer presents a notable obstacle, with indications pointing to the substantial role of circular RNAs (circRNAs) in this resistance. Nevertheless, the precise mechanisms through which circRNAs govern resistance are not yet fully understood. Our findings demonstrate that circUGGT2 is significantly upregulated in bladder cancer, facilitating cancer cell migration and invasion. Additionally, our analysis of eighty patient outcomes revealed a negative correlation between circUGGT2 expression levels and prognosis. Using circRNA pull-down assays, mass spectrometry analyses, and RNA Immunoprecipitation (RIP), it was shown that circUGGT2 interacts with the KU heterodimer, consisting of KU70 and KU80. Both KU70 and KU80 are critical components of the non-homologous end joining (NHEJ) pathway, which plays a role in CDDP resistance. Flow cytometry was utilized in this study to illustrate the impact of circUGGT2 on the sensitivity of bladder cancer cell lines to CDDP through its interaction with KU70 and KU80. Additionally, a reduction in the levels of DNA repair factors associated with the NHEJ pathway, such as KU70, KU80, DNA-PKcs, and XRCC4, was observed in chromatin of bladder cancer cells following circUGGT2 knockdown post-CDDP treatment, while the levels of DNA repair factors in total cellular proteins remained constant. Thus, the promotion of CDDP resistance by circUGGT2 is attributed to its facilitation of repair factor recruitment to DNA breaks via interaction with the KU heterodimer. Furthermore, our study demonstrated that knockdown of circUGGT2 resulted in reduced levels of γH2AX, a marker of DNA damage response, in CDDP-treated bladder cancer cells, implicating circUGGT2 in the NHEJ pathway for DNA repair.

[Mechanism of Shenling Baizhu Powder on treatment of alcoholic liver disease by regulating TLR4/NLRP3 pathway].

This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3Ⅱ). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1ß, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3Ⅱ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.

Prevalence and influencing factors of kinesiophobia in older patients with primary osteoporosis: A cross-sectional survey.

AIM: To explore the prevalence of kinesiophobia in older patients with primary osteoporosis and analyze its influencing factors. METHODS: A cross-sectional survey was conducted among 221 older patients with primary osteoporosis in a general hospital in Kunming, China. Data were collected through a sociodemographic-clinical questionnaire, Tampa Scale for Kinesiophobia-11 (TSK-11), Global Pain Scale (GPS), Five Facets Mindfulness Questionnaire-Short Form (FFMQ-SF), and Hospital Anxiety and Depression Scale (HADS). SPSS 27.0 software was utilized for univariate and binary logistic regression analyses. RESULTS: The findings revealed that the prevalence of kinesiophobia in this study was 57.01 %. Age, history of fractures, chronic obstructive pulmonary disease (COPD), lumbar disc herniation, chronic pain, mindfulness, anxiety, and depression were identified as significant influencing factors of kinesiophobia in the binary logistic regression analyses. CONCLUSION: Healthcare professionals should be attentive to occurrence of kinesiophobia. Timely measures should be implemented to improve pain, anxiety and depression, and employ mindfulness interventions to mitigate kinesiophobia.

Medical service quality evaluation based on LDA and sentiment analysis: Examples of seven chronic diseases.

Objective: In this article, we investigate how chronic noncommunicable disease (CND) patients evaluate the medical service, and what obstacles exist in this process, which is useful for hospitals to improve efficiency and enhance patient satisfaction. Methods: Based on the total number of CND patients in China, 7 CNDs were selected as the evaluation objects, and then selected the Haodaifu website as the data source, crawled 15,682 medical service reviews, then the 9 themes were analyzed by the LDA theme model. The evaluation index system of six indicators was constructed based on quality management theory. The binary long short-term memory model was used to analyze the sentiment, and the entropy-valued, TOPSIS and gray correlation model was implemented for medical service quality evaluation; the barrier model was used to find out the key factors limiting medical services. Results: (a) Hypertension was rated at a good level in the degree of gray correlation closeness, bronchitis was rated at a low level and the rest were at an intermediate level. (b) The first two overall barriers were the hospitalization process and registration services which occupy about 30%, respectively. This implies that hospitals should focus on providing registration services and inpatient settings in the future. Conclusion: To promote hospitals to provide better services for patients with CNDs and improve patient satisfaction with medical care. And it is necessary to optimize medical services fundamentally by optimizing the inpatient process and improving the registration process to improve efficiency.

Sub-Second Long Lifetime Triplet Exciton Reservoir for Highly Efficient and Stable Organic Light-Emitting Diode.

In organic light-emitting diode (OLED), achieving high efficiency requires effective triplet exciton confinement by carrier-transporting materials, which typically have higher triplet energy (ET ) than the emitter, leading to poor stability. Here, an electron-transporting material (ETM), whose ET is 0.32 eV lower than that of the emitter is reported. In devices, it surprisingly exhibits strong confinement effect and generates excellent efficiency. Additionally, the device operational lifetime is 4.9 times longer than the device with a standard ETM, 1,3,5-tri(1-phenyl-1H-benzo[d]imidazol-2-yl) phenyl (whose ET 0.36 eV is higher than the emitter). This anomalous finding is ascribed to the exceptionally long triplet state lifetime (≈0.2 s) of the ETM. It is named as long-lifetime triplet exciton reservoir effect. The systematic analysis reveals that the long triplet lifetime of ETM can compensate the requirement for high ET with the help of endothermic energy transfer. Such combination of low ET and long lifetime provides equivalent exciton confinement effect and high molecular stability simultaneously. It offers a novel molecular design paradigm for breaking the dilemma between high efficiency and prolonged operational lifetime in OLEDs.

Perceptions Toward Exercise or Mindful Exercise Participation Among Patients With Primary Osteoporosis: A Qualitative Study.

Exercise is significantly beneficial for patients with osteoporosis. However, physiological and psychological factors such as pain and kinesiophobia prevent patients from participating in exercise. Therefore, it is important to understand how these patients perceive participation in exercise. This qualitative study was conducted in China using conventional content analysis. Using a purposeful sampling method, 17 patients with primary osteoporosis were recruited. Data were collected through a semi-structured interview and managed using ATLAS.ti 21. Nine generic categories were developed from 26 subcategories and two main categories were identified: Barriers and facilitators, support systems, network resources, positive emotions, and reactions were the facilitators for exercise in this study. In addition, mindful exercise was positively viewed by the patients. Inefficient awareness, weak support systems, and burdens were identified as barriers. To improve compliance in clinical practice, targeted exercise protocols should be developed for patients based on these perceptions.

Temporal and Emotional Variations in People's Perceptions of Mass Epidemic Infectious Disease After the COVID-19 Pandemic Using Influenza A as an Example: Topic Modeling and Sentiment Analysis Based on Weibo Data.

BACKGROUND: The COVID-19 pandemic has had profound impacts on society, including public health, the economy, daily life, and social interactions. Social distancing measures, travel restrictions, and the influx of pandemic-related information on social media have all led to a significant shift in how individuals perceive and respond to health crises. In this context, there is a growing awareness of the role that social media platforms such as Weibo, among the largest and most influential social media sites in China, play in shaping public sentiment and influencing people's behavior during public health emergencies. OBJECTIVE: This study aims to gain a comprehensive understanding of the sociospatial impact of mass epidemic infectious disease by analyzing the spatiotemporal variations and emotional orientations of the public after the COVID-19 pandemic. We use the outbreak of influenza A after the COVID-19 pandemic as a case study. Through temporal and spatial analyses, we aim to uncover specific variations in the attention and emotional orientations of people living in different provinces in China regarding influenza A. We sought to understand the societal impact of large-scale infectious diseases and the public's stance after the COVID-19 pandemic to improve public health policies and communication strategies. METHODS: We selected Weibo as the data source and collected all influenza A-related Weibo posts from November 1, 2022, to March 31, 2023. These data included user names, geographic locations, posting times, content, repost counts, comments, likes, user types, and more. Subsequently, we used latent Dirichlet allocation topic modeling to analyze the public's focus as well as the bidirectional long short-term memory model to conduct emotional analysis. We further classified the focus areas and emotional orientations of different regions. RESULTS: The research findings indicate that, compared with China's western provinces, the eastern provinces exhibited a higher volume of Weibo posts, demonstrating a greater interest in influenza A. Moreover, inland provinces displayed elevated levels of concern compared with coastal regions. In addition, female users of Weibo exhibited a higher level of engagement than male users, with regular users comprising the majority of user types. The public's focus was categorized into 23 main themes, with the overall emotional sentiment predominantly leaning toward negativity (making up 7562 out of 9111 [83%] sentiments). CONCLUSIONS: The results of this study underscore the profound societal impact of the COVID-19 pandemic. People tend to be pessimistic toward new large-scale infectious diseases, and disparities exist in the levels of concern and emotional sentiments across different regions. This reflects diverse societal responses to health crises. By gaining an in-depth understanding of the public's attitudes and focal points regarding these infectious diseases, governments and decision makers can better formulate policies and action plans to cater to the specific needs of different regions and enhance public health awareness.

Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation.

CXCR4 is a key regulator of the development of NK cells and DCs, both of which play an important role in early placental development and immune tolerance at the maternal-fetal interface. However, the role of CXCR4 in pregnancy is not well understood. Our study demonstrates that adult-induced global genetic CXCR4 deletion, but not uterine-specific CXCR4 deletion, was associated with increased pregnancy resorptions and decreased litter size. CXCR4-deficient mice had decreased NK cells and increased granulocytes in the decidua, along with increased leukocyte numbers in peripheral blood. We found that CXCR4-deficient mice had abnormal decidual NK cell aggregates and NK cell infiltration into trophoblast areas beyond the giant cell layer. This was associated with low NK cell expression of granzyme B, a NK cell granule effector, indicative of NK cell dysfunction. Pregnancy failure in these mice was associated with abnormalities in placental vascular development and increased placental expression of inflammatory genes. Importantly, adoptive BM transfer of WT CXCR4+ BM cells into CXCR4-deficient mice rescued the reproductive deficits by normalizing NK cell function and mediating normal placental vascular development. Collectively, our study found an important role for maternal CXCR4 expression in immune cell function, placental development, and pregnancy maintenance.

P4HA2-mediated HIF-1α stabilization promotes erdafitinib-resistance in FGFR3-alteration bladder cancer.

Erdafitinib is a novel fibroblast growth factor receptor (FGFR) inhibitor that has shown great therapeutic promise for solid tumor patients with FGFR3 alterations, especially in urothelial carcinoma. However, the mechanisms of resistance to FGFR inhibitors remain poorly understood. In this study, we found Erdafitinib could kill cells by inducing incomplete autophagy and increasing intracellular reactive oxygen species levels. We have established an Erdafitinib-resistant cell line, RT-112-RS. whole transcriptome RNA sequencing (RNA-Seq) and Cytospace analysis performed on Erdafitinib-resistant RT-112-RS cells and parental RT-112 cells introduced P4HA2 as a linchpin to Erdafitinib resistance. The gain and loss of function study provided evidence for P4HA2 conferring such resistance in RT-112 cells. Furthermore, P4HA2 could stabilize the HIF-1α protein which then activated downstream target genes to reduce reactive oxygen species levels in bladder cancer. In turn, HIF-1α could directly bind to P4HA2 promoter, indicating a positive loop between P4HA2 and HIF-1α in bladder cancer. These results suggest a substantial role of P4HA2 in mediating acquired resistance to Erdafitinib and provide a potential target for bladder cancer treatment.

Dry and wet experiments reveal the significant role of FUT11 in clear cell renal cell carcinoma.

BACKGROUND: Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations. METHODS: Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo. RESULTS: The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results. CONCLUSIONS: In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.

Vacuum Foam Drying Method Improved the Thermal Stability and Long-Term Shelf Life of a Live Attenuated Newcastle Disease Virus Vaccine.

Vaccines used for managing Newcastle disease virus (NDV) rely heavily on cold chain, and this results in major constraints in their successful application, shipping, and storage. This study was undertaken to improve the thermotolerance properties of live attenuated NDV vaccines using vacuum foam drying (VFD) technology. The live attenuated NDV vaccine formulated in 15% trehalose, 2.5% gelatin, 0.05% pluronic, and 25 mmol/L potassium phosphate buffer (T5) and dried using VFD showed improved heat tolerance in comparison to the vaccine formulated in T5 as well, but dried using freeze-drying (FD) method. The T5-formulated VFD vaccine was stored at 37°C for 120 days, 45°C for 7 days, and 60°C for 3 days; the virus titer loss decreased by no more than 1.0 Log10. In contrast, the FD vaccine prepared in T5 could only be stored at 37°C for 7-10 days. Furthermore, the T5-formulated NDV-VFD vaccine remained infectious when heated at 100°C for 30 min. Shelf-life studies confirmed the improved thermal tolerance of the T5-formulated NDV-VFD vaccine since it could be stably stored at 2-8°C for 42 months and 25°C for 15 months. Moreover, immunization of 1-month-old specific pathogen-free (SPF) chickens with the T5-formulated NDV-VFD vaccine stored at 25 and 37°C could produce hemagglutination inhibition (HI) antibody levels comparable to those of commercial NDV-FD vaccines, which require strict adherence to the cold chain. In conclusion, not only did the VFD technology improve the thermostability and long-term shelf life of the vaccine, it also maintained its immunogenicity.

Career maturity, psychological resilience, and professional self-concept of nursing students in China: A nationwide cross-sectional study.

BACKGROUND: The career maturity of nursing students has an influence on their individual career choices and their personal career development trajectory. Psychological resilience and a positive professional self-concept might help students adjust and adapt to their nursing careers. Therefore, there is a growing need to assess and develop these psychological concepts among nursing students. PURPOSE: This study aimed to determine the levels of career maturity, psychological resilience, and professional self-concept among Chinese senior nursing students as well as to examine the relationships between the variables. METHODS: A cross-sectional survey was carried out across six undergraduate medical colleges in China from May to August 2021. A total of 1223 full-time final year undergraduate nursing students who fulfilled the study criteria were recruited using the universal sampling method. Self-administered questionnaires including the Career Maturity Scale (CMS), Connor-Davidson Resilience Scale-2 (CD-RISC2), and Professional Self-Concept of Nurses Instrument (PSCNI) were used for data collection. For results reporting, the study complied with the STROBE checklist. RESULTS: The participants' career maturity, professional self-concept, and psychological resilience were found to be at moderate levels. Experience of being a class leader and actively choosing a nursing major were factors that had significant influence on students' career maturity, professional self-concept, and psychological resilience. Pearson's correlation analysis revealed career maturity to be closely related to professional self-concept and psychological resilience (p < 0.01). Results of structural equation modelling analyses revealed a good fit to the data based on various fit indices (χ2/df = 6.18, GFI = 0.926, CFI = 0.915, IFI = 0.957, RMSEA = 0.058). Nursing students with positive professional self-concepts demonstrated higher psychological resilience, which in turn influenced their career maturity. CONCLUSIONS: The results of this study provide the initial indications for an extended career maturity model. A positive professional self-concept and psychological resilience has the potential to improve the career maturity of nursing students. The study findings provide a basis for nursing educators to focus on improving the professional self-concept and psychological resilience of nursing students.

Case Report: Extensive Temporal Bone Invasion in a Giant Vestibular Schwannoma.

Background: Rare giant vestibular schwannomas (GVSs) invade the temporal bone extensively, which carries unique risks for surgery owing to their complicated relationship with adjacent structures, difficult dissection of the temporal bone, and high risk of complications. The underlying mechanism of this invasive behavior remains unknown. Case description: We report on a 28-year-old woman who presented with typical hearing loss and facial paralysis (House-Brackmann II). Magnetic resonance imaging exhibited a giant mass (∼5.0 cm) in the right cerebellopontine angle (CPA), petrous apex, and middle cranial fossa. Her primary diagnosis was GVS with petrous apex invasion. With the aid of presurgical imaging reconstruction and intraoperative facial nerve monitoring, we adopted a sequential therapeutic strategy, which included microsurgery for the CPA lesion followed by gamma knife radiosurgery (GKRS) for the petrous mass. During follow-up, stable tumor control was achieved with functional preservation of the facial nerve and no other complications. The postoperative immunohistochemical examination demonstrated dramatic intratumoral inflammation, which suggested its potential role in bony erosion. We reviewed the literature of large vestibular schwannoma with a petrous invasion and further discussed its treatment. Conclusion: Microsurgery remains the top therapeutic strategy for GVS. However, gross total resection with functional preservation of cranial nerves is challenging to achieve once the temporal bone is involved. In this case, we applied a planned and sequential approach of microsurgery and GKRS with a promising outcome, which highlighted this combinational strategy in this rare situation. In addition, pathological examination suggested that intratumoral inflammation might play a role in the bony erosion of GVS. Longer observation and more cases are needed to further investigate its molecular mechanism and treatment plan.

Identification of ISG15 and ZFP36 as novel hypoxia- and immune-related gene signatures contributing to a new perspective for the treatment of prostate cancer by bioinformatics and experimental verification.

BACKGROUND: Prostatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients. METHODS: The hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays. RESULTS: A hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells. CONCLUSION: Our study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa.

Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus†.

Bone marrow-derived progenitor cells (BMDPCs) are mobilized to the circulation in pregnancy and get recruited to the pregnant decidua where they contribute functionally to decidualization and successful implantation. However, the molecular mechanisms underlying BMDPCs recruitment to the decidua are unknown. CXCL12 ligand and its CXCR4 receptor play crucial roles in the mobilization and homing of stem/progenitor cells to various tissues. To investigate the role of CXCL12-CXCR4 axis in BMDPCs recruitment to decidua, we created transgenic GFP mice harboring CXCR4 gene susceptible to tamoxifen-inducible Cre-mediated ablation. These mice served as BM donors into wild-type C57BL/6 J female recipients using a 5-fluorouracil-based nongonadotoxic submyeloablation to achieve BM-specific CXCR4 knockout (CXCR4KO). Successful CXCR4 ablation was confirmed by RT-PCR and in vitro cell migration assays. Flow cytometry and immunohistochemistry showed a significant increase in GFP+ BM-derived cells (BMDCs) in the implantation site as compared to the nonpregnant uterus of control (2.7-fold) and CXCR4KO (1.8-fold) mice. This increase was uterus-specific and was not observed in other organs. This pregnancy-induced increase occurred in both hematopoietic (CD45+) and nonhematopoietic (CD45-) uterine BMDCs in control mice. In contrast, in CXCR4KO mice there was no increase in nonhematopoietic BMDCs in the pregnant uterus. Moreover, decidual recruitment of myeloid cells but not NK cells was diminished by BM CXCR4 deletion. Immunofluorescence showed the presence of nonhematopoietic GFP+ cells that were negative for CD45 (panleukocyte) and DBA (NK) markers in control but not CXCR4KO decidua. In conclusion, we report that CXCR4 expression in nonhematopoietic BMDPCs is essential for their recruitment to the pregnant decidua.

Cardiovascular risk profile and clinical characteristics of diabetic patients: a cross-sectional study in China.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in adults with type 2 diabetes (T2D). The aim of this study was to determine the CV risk in Chinese patients with T2D based on the 2019 European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) guidelines on diabetes, pre-diabetes, and CV diseases. METHODS: A total of 25,411 patients with T2D, who participated in the study of China Cardiometabolic Registries 3B study, were included in our analysis. We assessed the proportions of patients in each CV risk category according to 2019 ESC/EASD guidelines. RESULTS: Based on the 2019 ESC/EASD guidelines, 16,663 (65.6%), 1895 (7.5%), and 152 (0.6%) of patients were included in "very high risk," "high risk," and "moderate risk" categories, respectively. The proportions of patients in each category varied based on age, sex, body mass index, and duration. While 58.7% (9786/16,663) of elderly patients were classified to "very high risk" group, 89.6% (3732/4165) of patients with obesity were divided into "very high risk" group. Almost all patients with a duration of diabetes >10 years had "very high risk" or "high risk." However, 6701 (26.4%) of Chinese T2D patients, who had shorter duration, and one or two risk factors, could not be included in any category (the "unclear risk" category). CONCLUSIONS: In China, most patients with T2D have "very high" or "high" CV risk based on 2019 ESC/EASD guidelines. However, the risk of patients in "unclear risk" group needs to be further classified.

Progress of miRNA in male infertility: how close are we to noninvasive and accurate diagnostic markers? Systematic review and meta-analysis.

Aim: To determine the accuracy of miRNA as a biomarker in male infertility diagnosis. Methods: After a systematic literature search was performed in several databases, 1263 participants in eight studies through May 2020 were included. Publication bias was identified by Deeks funnel plot asymmetry test. Likelihood ratio scattergram and Fagan's nomogram were employed to judge the application value of a diagnosis. Threshold effect, sensitivity and regression analysis were performed to explore possible sources of potential heterogeneity. Results: Subgroup analysis demonstrated that the use of multiple miRNAs and seminal plasma-derived miRNAs showed high sensitivity and diagnostic odds ratios. Conclusion: miRNAs show great potential as novel diagnostic biomarkers for infertility.

Bone marrow-derived progenitor cells contribute to remodeling of the postpartum uterus.

Endometrial stem/progenitor cells play a role in postpartum uterine tissue regeneration, but the underlying mechanisms are poorly understood. While circulating bone marrow (BM)-derived cells (BMDCs) contribute to nonhematopoietic endometrial cells, the contribution of BMDCs to postpartum uterus remodeling is unknown. We investigated the contribution of BMDCs to the postpartum uterus using 5-fluorouracil-based nongonadotoxic BM transplant from green fluorescent protein (GFP) donors into wild-type C57BL/6J female mice. Flow cytometry showed an influx of GFP+ cells to the uterus immediately postpartum accounting for 28.7% of total uterine cells, followed by a rapid decrease to prepregnancy levels. The majority of uterine GFP+ cells were CD45+ leukocytes, and the proportion of nonhematopoietic CD45-GFP+ cells peaked on postpartum day (PPD) 1 (17.5%). Immunofluorescence colocalization of GFP with CD45 pan-leukocyte and F4/80 macrophage markers corroborated these findings. GFP+ cells were found mostly in subepithelial stromal location. Importantly, GFP+ cytokeratin-positive epithelial cells were found within the luminal epithelium exclusively on PPD1, demonstrating direct contribution to postpartum re-epithelialization. A subset (3.2%) of GFP+ cells were CD31+CD45- endothelial cells, and found integrated within blood vessel endothelium. Notably, BM-derived GFP+ cells demonstrated preferential proliferation (PCNA+) and apoptosis (TUNEL+) on PPD1 vs resident GFP- cells, suggesting an active role for BMDCs in rapid tissue turnover. Moreover, GFP+ cells gradually acquired cell senescence together with decreased proliferation throughout the postpartum. In conclusion, BM-derived progenitors were found to have a novel nonhematopoietic cellular contribution to postpartum uterus remodeling. This contribution may have an important functional role in physiological as well as pathological postpartum endometrial regeneration.

Comprehensive analysis of the functional and prognostic value of E2F transcription factors in human prostate cancer through data mining and experimental validation.

BACKGROUND: A growing body of evidence shows that E2F transcription factors play a significant role in the tumorigenesis of prostate cancer. However, their functional and prognostic value has not been fully illustrated. Therefore, we used bioinformatics methods to further analyze the possible roles of E2F transcription factors in the development and progression of prostate cancer. METHODS: We explored the expression levels of E2F transcription factors using data from The Cancer Genome Atlas (TCGA) and Oncomine database in paired and unpaired samples. The clinical correlation and prognostic value of E2F transcription factors were assessed. Using the R package "pROC", we judged the diagnostic value of E2F transcription factors. The online website tool cBioPortal was also employed to find possible gene alterations of E2F transcription factors in samples from TCGA. The R package "clusterprofiler" was used to conduct functional analysis. Moreover, we also used the Tumor Immune Estimation Resource to search for the associations between E2F transcription factors and the infiltration levels of 6 kinds of immune cells. Finally, quantitative real-time polymerase chain reaction (PCR) was conducted to validate the expression levels of E2F transcription factors in human paired prostate tissues. RESULTS: E2F1/2/3/5 messenger RNA (mRNA) expression levels were higher in prostate cancer tissues than in normal tissues, while E2F4 and E2F6 mRNA expression levels were lower (P<0.05). All E2F transcription factors were associated with clinical parameters. Kaplan-Meier analysis revealed that E2F1/4/6/8 were notably associated with the overall survival of patients with prostate cancer (P<0.05). Receiver operating characteristic (ROC) curve results showed that except for E2F7, the other E2F transcription factors had diagnostic value for prostate cancer (P<0.05). We further found close associations between E2F transcription factors and the infiltration levels of immune cells. The results of quantitative real-time PCR were consistent with those from public databases. CONCLUSIONS: E2F transcription factor family members are differentially expressed in prostate cancer and are significantly related to the prognosis of patients, suggesting that they may be adopted as biomarkers for prognosis prediction and the treatment of prostate cancer.