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Ovarian cancer is the fifth leading cause of cancer-related mortality in women worldwide. Despite the development of technologies over decades to improve the diagnosis and treatment of patients with ovarian cancer, the survival rate remains dismal, mainly because most patients are diagnosed at a late stage. Traditional treatment methods and biomarkers such as cancer antigen-125 as a cancer screening tool lack specificity and cannot offer personalized combinatorial therapy schemes. Circulating tumor DNA (ctDNA) is a promising biomarker for ovarian cancer and can be detected using a noninvasive liquid biopsy. A wide variety of ctDNA applications are being elucidated in multiple studies for tracking ovarian carcinoma during diagnostic and prognostic evaluations of patients and are being integrated into clinical trials to evaluate the disease. Furthermore, ctDNA analysis may be used in combination with multiple “omic” techniques to analyze proteins, epigenetics, RNA, nucleosomes, exosomes, and associated immune markers to promote early detection. However, several technical and biological hurdles impede the application of ctDNA analysis. Certain intrinsic features of ctDNA that may enhance its utility as a biomarker are problematic for its detection, including ctDNA lengths, copy number variations, and methylation. Before the development of ctDNA assays for integration in the clinic, such issues are required to be resolved since these assays have substantial potential as a test for cancer screening. This review focuses on studies concerning the potential clinical applications of ctDNA in ovarian cancer diagnosis and discusses our perspective on the clinical research aimed to treat this daunting form of cancer.

Increasing evidence has revealed that miR‐199a‐5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR‐199a‐5p weakened motility and invasion of breast cancer cells MCF‐7 and MDA‐MB‐231. Upregulation of Ets‐1 increased breast cancer cell invasion, but the mechanism by which miR‐199a‐5p modulates activation of Ets‐1 in breast cancer was not clarified. We investigated the relationship between miR‐199a‐5p and Ets‐1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets‐1 expression was inversely correlated with endogenous miR‐199a‐5p. Overexpression of miR‐199a‐5p reduced the mRNA and protein levels of Ets‐1 in MCF‐7 and MDA‐MB‐231 cells, whereas anti‐miR‐199a‐5p elevated Ets‐1. siRNA‐mediated Ets‐1 knockdown phenocopied the inhibition invasion of miR‐199a‐5p in vitro. Moreover, luciferase reporter assay revealed that miR‐199a‐5p directly targeted 3′‐UTR of Ets‐1 mRNA. This research revealed that miR‐199a‐5p could descend the levels of β1 integrin by targeting 3′‐UTR of Ets‐1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of β1 integrin through miR‐199a‐5p‐mediated Ets‐1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR‐199a‐5p in breast cancer invasion. Our results provide insight into the regulation of β1 integrin through miR‐199a‐5p‐mediated Ets‐1 silence and help in designing new therapeutic strategies to inhibit signal pathways induced by miR‐199a‐5p in breast cancer invasion.

While polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea (OSA), its limited availability means that many patients remain undiagnosed. This study seeks to evaluate whether CHI3L1-Ab could serve as a diagnostic biomarker for OSA. A total of 366 individuals, including 333 OSA patients and 33 healthy controls, were recruited for this study, all of whom underwent polysomnography. Enzyme-linked immunosorbent assay (ELISA) was used to measure CHI3L1-Ab levels, and clinical factors were analyzed to assess their relationship with CHI3L1-Ab expression. OSA patients exhibited significantly higher CHI3L1-Ab levels compared to healthy controls ( P  < 0.05), with an area under the curve (AUC) of 0.721. Subgroup analysis revealed the highest AUC of 0.735 (95% CI 0.637–0.832) in patients with severe OSA. Logistic regression analysis, which incorporated age, BMI and CHI3L1-Ab levels, demonstrated strong predictive performance with an AUC of 0.846 (95% CI 0.815–0.942). The corresponding nomogram allowed individualized risk estimation based on these predictors. The combination of CHI3L1-Ab levels, age and BMI demonstrated strong predictive accuracy in distinguishing OSA from healthy individuals. These findings also suggest that elevated CHI3L1-Ab levels could serve as an independent diagnostic biomarker for OSA.

ObjectiveOur study aims to present a summary of the clinicopathological characteristics of patients affected by the coronavirus disease 2019 (COVID-19) that can be used as a reference for further research and clinical decisions.DesignStudies were included in the meta-analysis if they had cohort, case–control or case series designs and provided sufficient details on clinical symptoms, laboratory outcomes and asymptomatic patients.SettingPubMed, Embase, Chinese Biomedical Literature Database, Wanfang, China Science and Technology Journal Database and China National Knowledge Infrastructure databases were electronically searched to identify related studies published between 1 January 2020 and 16 March 2020. Three reviewers independently examined the literature, extracted relevant data and assessed the risk of publication bias before including the studies in the meta-analysis.ParticipantsThe confirmed cases of COVID-19.ResultsA total of 55 unique retrospective studies involving 8697 patients with COVID-19 were identified. Meta-analysis showed that a higher proportion of infected patients were male (53.3%), and the two major symptoms observed were fever (78.4%) and cough (58.3%). Other common symptoms included fatigue (34%), myalgia (21.9%), expectoration (23.7%), anorexia (22.9%), chest tightness (22.9%) and dyspnoea (20.6%). Minor symptoms included nausea and vomiting (6.6%), diarrhoea (8.2%), headache (11.3%), pharyngalgia (11.6%), shivering (15.2%) and rhinorrhea (7.3%). About 5.4% of the patients were asymptomatic. Most patients showed normal leucocyte counts (64.7%) and elevated C reactive protein levels (65.9%). Lymphopaenia was observed in about 47.6% of the infected patients, along with abnormal levels of myocardial enzymes (49.4%) and liver function (26.4%). Other findings included leucopenia (23.5%), elevated D-dimer (20.4%), elevated erythrocyte sedimentation rate (20.4%), leucocytosis (9.9%), elevated procalcitonin (16.7%) and abnormal renal function (10.9%).ConclusionsThe most commonly experienced symptoms of patients with COVID-19 were fever and cough. Myalgia, anorexia, chest tightness and dyspnoea were found in some patients. A relatively small percentage of patients were asymptomatic and could act as carriers of the disease. Most patients showed normal leucocyte counts, elevated levels of C reactive protein and lymphopaenia, confirming the viral origin of the disease.

Background Dysfunctional p53 signaling is one of the major causes of hepatocellular carcinoma (HCC) tumorigenesis and development, but the mechanisms underlying p53 inactivation in HCC have not been fully clarified. The role of Krüppel-associated box (KRAB)-type zinc-finger protein ZNF498 in tumorigenesis and the underlying mechanisms are poorly understood. Methods Clinical HCC samples were used to assess the association of ZNF498 expression with clinicopathological characteristics and patient outcomes. A mouse model in which HCC was induced by diethylnitrosamine (DEN) was used to explore the role of ZNF498 in HCC initiation and progression. ZNF498 overexpression and knockdown HCC cell lines were employed to examine the effects of ZNF498 on cellular proliferation, apoptosis, ferroptosis and tumor growth. Western blotting, immunoprecipitation, qPCR, luciferase assays and flow cytometry were also conducted to determine the underlying mechanisms related to ZNF498 function. Results ZNF498 was found to be highly expressed in HCC, and increased ZNF498 expression was positively correlated with advanced pathological grade and poor survival in HCC patients. Furthermore, ZNF498 promoted DEN-induced hepatocarcinogenesis and progression in mice. Mechanistically, ZNF498 directly interacted with p53 and suppressed p53 transcriptional activation by inhibiting p53 Ser46 phosphorylation. ZNF498 competed with p53INP1 for p53 binding and suppressed PKCδ- and p53INP1-mediated p53 Ser46 phosphorylation. In addition, functional assays revealed that ZNF498 promoted liver cancer cell growth in vivo and in vitro in a p53-dependent manner. Moreover, ZNF498 inhibited p53-mediated apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation. Conclusions Our results strongly suggest that ZNF498 suppresses apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation in hepatocellular carcinogenesis, revealing a novel ZNF498-PKCδ-p53INP1-p53 axis in HCC cells that would enrich the non-mutation p53-inactivating mechanisms in HCC.

Fibronectin (FN) has been recognized as the key element in promoting cell adhesion, migration and oncogenic transformation. αvβ6 integrin binds with FN in an RGD-dependent manner and is associated with invasion and poor prognosis in many types of cancers. The extracellular matrix (ECM) is commonly degraded and becomes disorganized in cancers. Previous studies have shown that FN can be degraded into fragments by MMP-9 in vitro; MMP-9 expression is upregulated in breast cancer, therefore, the role of degraded FN in breast cancer progression needs to be investigated. In the present study, expression of β6 integrin in breast cancer tissues was analyzed. The data were quite consistent with the hypothesis that β6 integrin expression is an indicator of poor prognosis. Cell surface expression of β6 integrin was correlated with the invasive behavior of the breast cancer cell lines. MMP-9-degraded FN was used to explore its effects on cell invasion and expression of β6 integrin. The results indicated that MMP-9-degraded FN can adjust constituents of the αvβ6 heterodimers at the early phase and significantly elevate amounts of β6 integrin subunits at a later period. To better elucidate the mechanism by which β6 integrin regulates FN-induced cell migration and invasion, we determined the expression and activity of the downstream kinases of β6 integrin, and elucidated that focal adhesion kinase (FAK)-Src interaction promoted the invasion and migration of breast cancer cells after treatment of MMP-9-degraded FN through the Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways.

Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. Here we investigate and characterize RMs at different ages by conditionally labeling and ablating RMs populations in several transgenic lines. We find that RMs expand and mature in parallel with renal growth after birth, and are mainly derived from fetal liver monocytes before birth, but self-maintain through adulthood with contribution from peripheral monocytes. Moreover, after the RMs niche is emptied, peripheral monocytes rapidly differentiate into BMRMs, with the CX3CR1/CX3CL1 signaling axis being essential for the maintenance and regeneration of both EMRMs and BMRMs. Lastly, we show that EMRMs have a higher capacity for scavenging immune complex, and are more sensitive to immune challenge than BMRMs, with this difference associated with their distinct glycolytic capacities. Renal macrophages (RMs) can be of bone marrow or embryonic origin, but their abundance, fate and metabolic profiles in physiological and pathogenic settings are still unclear. Here the authors show, by characterizing these two RMs in multiple transgenic mouse lines, that they exhibit distinct dynamics, homeostasis, immune activity, and metabolic properties.

Platelets are the second most abundant blood component after red blood cells and can participate in a variety of physiological and pathological functions. Beyond its traditional role in hemostasis and thrombosis, it also plays an indispensable role in inflammatory diseases. However, thrombocytopenia is a common hematologic problem in the clinic, and it presents a proportional relationship with the fatality of many diseases. Therefore, the prevention and treatment of thrombocytopenia is of great importance. The expression of Toll-like receptors (TLRs) is one of the most relevant characteristics of thrombopoiesis and the platelet inflammatory function. We know that the TLR family is found on the surface or inside almost all cells, where they perform many immune functions. Of those, TLR2 and TLR4 are the main stress-inducing members and play an integral role in inflammatory diseases and platelet production and function. Therefore, the aim of this review is to present and discuss the relationship between platelets, inflammation and the TLR family and extend recent research on the influence of the TLR2 and TLR4 pathways and the regulation of platelet production and function. Reviewing the interaction between TLRs and platelets in inflammation may be a research direction or program for the treatment of thrombocytopenia-related and inflammatory-related diseases.

BCSC-1 (breast cancer suppressor candidate-1), the official gene symbol VWA5A (von Willebrand factor A domain containing 5 A), is downregulated in a variety of cancer types including breast cancer. The role of BCSC-1 in tumorigenesis and the underlying mechanisms are poorly understood. One of the ways to predict a spectrum of functions of an unknown protein is to identify the protein-protein interaction network involving it. Flag-pLV-Neo-BCSC1 or the empty vector were stably transfected into breast cancer cells MCF-7. The levels of BCSC1 expression were identified by Western blotting. Co-immunoprecipitation assay coupled with liquid chromatography with tandem mass spectrometry (Co-IP-MS) and bioinformatic analysis were done to study protein-protein interactions. A subset of interacting proteins was validated by immunofluorescence (IF). IF was also conducted to determine the cell migration of BCSC-1. The pEGFP-C3 plasmids with full-length and truncated BCSC-1 were transiently transfected into breast cancer cells to identify domains of BCSC-1 guiding the subcellular location. 341 interacting partners of BCSC-1 were significantly enriched in Flag-BCSC-1 against negative control. These interactors included the lysosome and the proteasome related to proteostatic pathways, the peroxisome involved in lipid metabolism, endocytosis components in the vesicle transport pathway, and the regulation of actin cytoskeleton. STAT1, STAT3, and CDC42, identified among the interacting partners, co-localized with BCSC-1. In addition, BCSC-1 distributed to the leading edge of migrating breast cancer cells. VIT (vault protein inter-α-trypsin) domain of BCSC-1 is required in the regulation of cell migration. BCSC-1 might exert diverse functions through protein-protein interactions.

Aim Emergency department nurses experience varying degrees of mental workload due to various factors. The group with medium to high levels of mental workload requires particular attention. There is limited research on the potential profiles of mental workload among emergency department nurses. The purpose of this study was to identify different potential profiles of mental workload among emergency department nurses and analyze the influencing factors. Design A cross-sectional study. Methods This study followed the STROBE guidelines. The NASA-TLX scale was used to assess the mental workload of emergency department nurses, and latent profile analysis was employed to identify different potential profiles of their mental workload. Statistical methods, including Pearson’s chi-square test and logistic regression analysis, were performed to identify factors affecting the mental workload of emergency department nurses. Results A total of 305 emergency department nurses completed the survey, with the majority experiencing a moderate to severe mental workload. Mental workload was a complex and dynamic phenomenon influenced by many factors. The main factors affecting mental workload included age (year), marital status, monthly income (RMB), support style, coping style, and personality traits. Conclusion The study suggested that mental workload among emergency department nurses is widespread in China. Nursing managers should provide targeted interventions based on the mental workload profiles of emergency department nurses. It is also crucial to enhance support from family and friends for emergency department nurses in their professional endeavors. This support should facilitate the adoption of positive coping styles to effectively address challenges. Tailored interventions, based on individual personality traits, should be implemented to reduce mental workload and promote the growth of the emergency department nursing team.