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Background: Cardiac steatosis is an early yet overlooked feature of diabetic cardiomyopathy. There is no available therapy to treat this condition. Tyrosine kinase inhibitors (TKIs) are used as first or second-line therapy in different types of cancer. In cancer patients with diabetes mellitus, TKIs reportedly improved glycemic control, allowing insulin discontinuation. They also reduced liver steatosis in a murine model of non-alcoholic fatty liver disease. The present study aimed to determine the therapeutic effect of the second-generation TKI Dasatinib on lipid accumulation and cardiac function in obese, type 2 diabetic mice. We also assessed if the drug impacts extra-cardiac fat tissue depots. Methods: Two studies on 21-week-old male obese leptin receptor mutant BKS.Cg-+Leprdb/+Leprdb/OlaHsd (db/db) mice compared the effect of Dasatinib (5 mg/kg) and vehicle (10% DMSO + 90% PEG-300) given via gavage once every three days for a week or once every week for four weeks. Functional and volumetric indices were studied using echocardiography. Post-mortem analyses included the assessment of fat deposits and fibrosis using histology, and senescence using immunohistochemistry and flow cytometry. The anti-adipogenic action of Dasatinib was investigated on human bone marrow (BM)-derived mesenchymal stem cells (MSCs). Unpaired parametric or non-parametric tests were used to compare two and multiple groups as appropriate. Results: Dasatinib reduced steatosis and fibrosis in the heart of diabetic mice. The drug also reduced BM adiposity but did not affect other fat depots. These structural changes were associated with improved diastolic indexes, specifically the E/A ratio and non-flow time. Moreover, Dasatinib-treated mice had lower levels of p16 in the heart compared with vehicle-treated controls, suggesting an inhibitory impact of the drug on the senescence signalling pathway. In vitro, Dasatinib inhibited human BM-MSC viability and adipogenesis commitment. Conclusions: Our findings suggest that Dasatinib opposes heart and BM adiposity and cardiac fibrosis. In the heart, this was associated with favourable functional consequences, namely improvement in an index of diastolic function. Repurposing TKI for cardiac benefit could address the unmet need of diabetic cardiac steatosis. [ABSTRACT FROM AUTHOR]

CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution in RCC remain elusive. We confirmed the overexpression of circZBTB44 in RCC cells compared to normal kidney cell HK-2. CircZBTB44 knockdown suppressed the viability, proliferation, and migration of RCC cells and inhibited tumorigenesis in xenograft mouse models. Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) are two RNA binding proteins of circZBTB44. HNRNPC facilitated the translocation of circZBTB44 from nuclei to cytoplasm via m6A modification, facilitating the interaction of IGF2BP3 and circZBTB44 in the cytoplasm of RCC cells. Furthermore, circZBTB44 upregulated Hexokinase 3 (HK3) expression by binding to IGF2BP3 in RCC cells. HK3 exerted oncogenic effects on RCC cell malignant behaviors and tumor growth. In the co-culture of RCC cells with macrophages, circZBTB44 promoted M2 polarization of macrophages by up-regulating HK3. In summary, HNRNPC mediated circZBTB44 interaction with IGF2BP3 to up-regulate HK3, promoting the proliferation and migration of RCC cells in vitro and tumorigenesis in vivo. The results of the study shed new light on the targeted therapy of RCC. [ABSTRACT FROM AUTHOR]

Background: Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. Methods/design: This is a prospective, randomized, controlled trial and 132 patients aged 65–80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. Discussion: Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. Trial registration: Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn. [ABSTRACT FROM AUTHOR]

Background: Statin has been more and more widely used in chronic liver disease, however, existed studies have attained contradictory results. According to the present study, we aimed to test the efficacy and safety of statin via a meta-analysis.Methods: Different databases were searched for full-text publication based on inclusion and exclusion criteria. For data-pooling, fixed-effect model was applied if heterogeneity wasn't detected. Otherwise, random-effect model was adopted. Heterogeneity was detected by I squire (I2) test. All results of analysis were illustrated as forest plots. Publication bias was assessed using the Begg's adjusted rank correlation test. Standard mean difference (SMD) was calculated in continuous variables. Pooled hazard ratio or odds ratio was calculated in catergorical variables.Results: Seventeen clinical studies were finally included. Hepatic portal hemodynamic parameters were improved in statin users for a short-term response. For a long-term follow-up, statin treatment surprisingly decreased mortality rate (HR = 0.782, 95% CI: 0.718-0.846, I2 > 50%) and lower the occurrence of hepatocellular carcinoma (HR = 0.75, 95% CI: 0.64-0.86, I2 > 50%) in liver cirrhosis. Statin seemed not to decrease the risk of esophageal variceal bleeding and spontaneous bacterial peritonitis. However, statin was proved to decrease the risk of hepatic encephalopathy and ascites. Incidence of drug related adverse events didn't increase in statin users. Dose-dependent effects of statin on hepatocellular carcinoma development, decompensated cirrhosis events occurrence, and liver cirrhosis progression.Conclusion: Statin influenced parameters of hepatic portal vessel pressure in short-term treatment. Prognosis of liver cirrhosis benefited from statin treatment in long term follow-up. The efficacy and safety of statin in liver cirrhosis treatment is confirmed. To date, similar study is hardly seen before. [ABSTRACT FROM AUTHOR]

Background: It is generally believed that DNA methylation, as one of the most important epigenetic modifications, participates in the regulation of gene expression and plays an important role in the development of cancer, and there exits epigenetic heterogeneity among cancers. Therefore, this study tried to screen for reliable prognostic markers for different cancers, providing further explanation for the heterogeneity of cancers, and more targets for clinical transformation studies of cancer from epigenetic perspective.Methods: This article discusses the epigenetic heterogeneity of cancer in detail. Firstly, DNA methylation data of seven cancer types were obtained from Illumina Infinium HumanMethylation 450 K platform of TCGA database. Then, differential methylation analysis was performed in the promotor region. Secondly, pivotal gene markers were obtained by constructing the DNA methylation correlation network and the gene interaction network in the KEGG pathway, and 317 marker genes obtained from two networks were integrated as candidate markers for the prognosis model. Finally, we used the univariate and multivariate COX regression models to select specific independent prognostic markers for each cancer, and studied the risk factor of these genes by doing survival analysis.Results: First, the cancer type-specific gene markers were obtained by differential methylation analysis and they were found to be involved in different biological functions by enrichment analysis. Moreover, specific and common diagnostic markers for each type of cancer was sorted out and Kaplan-Meier survival analysis showed that there was significant difference in survival between the two risk groups.Conclusions: This study screened out reliable prognostic markers for different cancers, providing a further explanation for the heterogeneity of cancer at the DNA methylation level and more targets for clinical conversion studies of cancer. [ABSTRACT FROM AUTHOR]

Background: Innate immune pre-stimulation can prevent the development of depression-like behaviors in chronically stressed mice; however, whether the same stimulation prevents the development of anxiety-like behaviors in animals remains unclear. We addressed this issue using monophosphoryl lipid A (MPL), a derivative of lipopolysaccharide (LPS) that lacks undesirable properties of LPS but still keeps immune-enhancing activities.Methods: The experimental mice were pre-injected intraperitoneally with MPL before stress exposure. Depression was induced through chronic social defeat stress (CSDS). Behavioral tests were conducted to identify anxiety-like behaviors. Real-time polymerase chain reaction (PCR) and biochemical assays were employed to examine the gene and protein expression levels of pro-inflammatory markers.Results: A single MPL injection at the dose of 400 and 800 μg/kg 1 day before stress exposure prevented CSDS-induced anxiety-like behaviors, and a single MPL injection (400 μg/kg) five but not 10 days before stress exposure produced similar effect. The preventive effect of MPL on anxiety-like behaviors was also observed in CSDS mice who received a second MPL injection 10 days after the first MPL injection or a 4 × MPL injection 10 days before stress exposure. MPL pre-injection also prevented the production of pro-inflammatory cytokines in the hippocampus and medial prefrontal cortex in CSDS mice, and inhibiting the central immune response by minocycline pretreatment abrogated the preventive effect of MPL on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine productions in the brain.Conclusions: Pre-stimulation of the innate immune system by MPL can prevent chronic stress-induced anxiety-like behaviors and neuroinflammatory responses in the brain in mice. [ABSTRACT FROM AUTHOR]

Background: The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer. Methods: Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR. Results: The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared. Conclusions: Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment. [ABSTRACT FROM AUTHOR]

Background: Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question. Results: We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability. Conclusion: STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases. Keypoints: STIF fosters the immune response of red blood cells to various pathogens, in particular SARS-CoV-2, via activation of the complement receptor on their membranes. STIF does not compromise the oxygen transport capacity or viability of red blood cells. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. Angiogenesis is a main contributing factor for tumorigenesis. E74-like transcription factor 5 (ELF5) has been verified to participate in the progression of different cancers and can regulate angiogenesis. This study was aimed to explore the functions of ELF5 in RCC. Methods: Bioinformatics tools were used to predict the expression of ELF5 in RCC. RT-qPCR was applied for testing ELF5 expression in RCC cells. Cell behaviors were evaluated by colony formation, CCK-8, and transwell assays. The tube formation assay was used for determining angiogenesis. Methylation-specific PCR (MSP) was utilized for measuring the methylation level of ELF5 in RCC cells. ChIP and luciferase reporter assays were applied for assessing the binding of ELF5 and ubiquitin-specific protease 3 (USP3). Co-IP and GST pull-down were utilized for detecting the interaction of WD40 and tetratricopeptide repeats 1 (WDTC1) and USP3. Ubiquitination level of WDTC1 was determined by ubiquitination assay. Results: ELF5 was lowly expressed in RCC cells and tissues. High expression of ELF5 expression notably suppressed RCC cell proliferative, migratory, and invasive capabilities, and inhibited angiogenesis. The tumor growth in mice was inhibited by ELF5 overexpression. ELF5 was highly methylated in RCC samples, and DNA methyltransferases (DNMTs) can promote hypermethylation level of ELF5 in RCC cells. ELF5 was further proved to transcriptionally activate USP3 in RCC. Moreover, USP3 inhibited WDTC1 ubiquitination. ELF5 can promote USP3-mediated WDTC1 stabilization. Additionally, WDTC1 silencing reversed the functions of ELF5 overexpression on RCC progression. Conclusion: Downregulation of ELF5 due to DNA hypermethylation inhibits RCC development though the USP3/WDTC1axis in RCC. [ABSTRACT FROM AUTHOR]

Background: Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question. Results: We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability. Conclusion: STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases. Keypoints: STIF fosters the immune response of red blood cells to various pathogens, in particular SARS-CoV-2, via activation of the complement receptor on their membranes. STIF does not compromise the oxygen transport capacity or viability of red blood cells. [ABSTRACT FROM AUTHOR]

Background: The introduction of multiparameter MRI and novel biomarkers has greatly improved the prediction of clinically significant prostate cancer (csPCa). However, decision-making regarding prostate biopsy and prebiopsy examinations is still difficult. We aimed to establish a quick and economic tool to improve the detection of csPCa based on routinely performed clinical examinations through an automated machine learning platform (AutoML). Methods: This study included a multicenter retrospective cohort and two prospective cohorts with 4747 cases from 9 hospitals across China. The multimodal data, including demographics, clinical characteristics, laboratory tests, and ultrasound reports, of consecutive participants were retrieved using extract-transform-load tools. AutoML was applied to explore potential data processing patterns and the most suitable algorithm to build the Prostate Cancer Artificial Intelligence Diagnostic System (PCAIDS). The diagnostic performance was determined by the receiver operating characteristic curve (ROC) for discriminating csPCa from insignificant prostate cancer (PCa) and benign disease. The clinical utility was evaluated by decision curve analysis (DCA) and waterfall plots. Results: The random forest algorithm was applied in the feature selection, and the AutoML algorithm was applied for model establishment. The area under the curve (AUC) value in identifying csPCa was 0.853 in the training cohort, 0.820 in the validation cohort, 0.807 in the Changhai prospective cohort, and 0.850 in the Zhongda prospective cohort. DCA showed that the PCAIDS was superior to PSA or fPSA/tPSA for diagnosing csPCa with a higher net benefit for all threshold probabilities in all cohorts. Setting a fixed sensitivity of 95%, a total of 32.2%, 17.6%, and 26.3% of unnecessary biopsies could be avoided with less than 5% of csPCa missed in the validation cohort, Changhai and Zhongda prospective cohorts, respectively. Conclusions: The PCAIDS was an effective tool to inform decision-making regarding the need for prostate biopsy and prebiopsy examinations such as mpMRI. Further prospective and international studies are warranted to validate the findings of this study. Trial registration: Chinese Clinical Trial Registry ChiCTR2100048428. Registered on 06 July 2021. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. Methods: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. Results: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = − 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. Conclusion: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. Methods: Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. Results: Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = − 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. Conclusions: Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. Methods: Based on a longitudinal study, 1082 participants receiving prenatal care in Ma'anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. Results: Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p < 0.05). As the number of SLEs increased, the risk of CAD increased (p for trend < 0.05). Specific types of SLEs were associated with CAD in different periods, while only interpersonal events were consistently associated with risks of CAD throughout the whole perinatal period. The joint effects of SLEs with ACEs on CAD were identified throughout the perinatal period, with the highest observed in the first trimester (aOR = 7.47, 95% CI: 3.73–14.95; p for trend < 0.001). Conclusion: Our study demonstrated independent associations of recent SLEs and their joint effects with ACEs with risks of perinatal CAD. SLEs combined with ACEs should be recognized as a major risk factor for perinatal CAD and managed at the earliest time to prevent and control CAD. [ABSTRACT FROM AUTHOR]

Background: Distant metastasis is the major cause of clear cell renal cell carcinoma (ccRCC)-associated mortality. However, molecular mechanisms involved in ccRCC metastasis remain to be fully understood. With the increasing appreciation of the role of long non-coding RNAs (lncRNAs) in cancer development, progression, and treatment resistance, the list of aberrantly expressed lncRNAs contributing to ccRCC pathogenesis is expanding rapidly. Methods: Bioinformatics analysis was carried out to interrogate publicly available ccRCC datasets. In situ hybridization and qRT-PCR assays were used to test lncRNA expression in human ccRCC tissues and cell lines, respectively. Chromatin immunoprecipitation and luciferase reporter assays were used to examine transcriptional regulation of gene expression. Wound healing as well as transwell migration and invasion assays were employed to monitor ccRCC cell migration and invasion in vitro. ccRCC metastasis was also examined using mouse models in vivo. RNA pulldown and RNA immunoprecipitation were performed to test RNA–protein associations, whereas RNA-RNA interactions were tested using domain-specific chromatin isolation by RNA purification. Results: MILIP expression was upregulated in metastatic compared with primary ccRCC tissues. The increased MILIP expression in metastatic ccRCC cells was driven by the transcription factor AP-2 gamma (TFAP2C). Knockdown of MILIP diminished the potential of ccRCC cell migration and invasion in vitro and reduced the formation of ccRCC metastatic lesions in vivo. The effect of MILIP on ccRCC cells was associated with alterations in the expression of epithelial-to-mesenchymal transition (EMT) hallmark genes. Mechanistically, MILIP formed an RNA-RNA duplex with the snail family transcriptional repressor 1 (Snai1) mRNA and bound to Y-box binding protein 1 (YBX1). This promoted the association between the YBX1 protein and the Snai1 mRNA, leading to increased translation of the latter. Snai1 in turn played an important role in MILIP-driven ccRCC metastasis. Conclusions: The TFAP2C-responsive lncRNA MILIP drives ccRCC metastasis. Targeting MILIP may thus represent a potential avenue for ccRCC treatment. [ABSTRACT FROM AUTHOR]

Background: The association between gestational diabetes mellitus (GDM) and perinatal depression (PND) remains controversial. Our study aimed to comprehensively assess this association in a longitudinal cohort study with repeated measurements of depression.Methods: Our cohort study was nested in a pilot study of an implementation study aiming to screen and manage perinatal depression within the primary health system in China. Women were recruited in the first trimester from May-September 2019 and followed four times up to 1 year postpartum. Data on sociodemographic characteristics and depression were collected using self-developed questionnaires incorporating the Edinburgh Postnatal Depression Scale (EPDS). Oral glucose tolerance test at 24 ~ 28 weeks and fasting plasma glucose (FPG) data were extracted from medical records. Depression throughout the whole period was divided into different trajectories. Associations of GDM with PND at different time periods and PND of different trajectories were determined by logistic regression. The path of association between blood glucose and depression over time was estimated with an autoregressive cross-lagged model.Results: In total, 1043 women were included in this analysis and 313 (30.0%) were diagnosed with GDM. The prevalence of depression in the first, second, and third trimesters and postpartum period were 17.2, 6.9, 6.8 and 9.0%, respectively. GDM was neither significantly associated with PND at any time point nor with any specific trajectory of depression. Except for autoregressive paths, no cross-lagged path of FPG and scores of EPDS was significant.Conclusions: Our study indicates no association between GDM/blood glucose and PND. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the clinical outcome of percutaneous kyphoplasty (PKP) assisted with mixed reality (MR) technology in treatment of osteoporotic vertebral compression fracture (OVCF) with intravertebral vacuum cleft (IVC). Method: Forty cases of OVCF with IVC undergoing PKP were randomized into a MR technology-assisted group (group A) and a traditional C-arm fluoroscopy group (group B). Both groups were performed PKP and evaluated by VAS scores, ODI scores, radiological evidence of vertebral body height, and kyphotic angle (KA) at pre-operation and post-operation. The volume of injected cement, fluoroscopy times, and operation time were recorded. And cases of non-PMMA-endplates-contact(NPEC) in radiological evidence was also recorded postoperatively. The clinical outcomes and complications were evaluated afterwards. All patients received 10 to 14 months follow-up, with an average of 12 months. Result: This MR-assisted group (group A) acquired more about the amount of the polymethyl methacrylate (PMMA) injection and postoperative vertebral height and less about postoperative KA, fluoroscopy times, and operation time compared with the control group (group B) (P < 0.05). The VAS scores and ODI scores in both groups have improved, but more significantly in group A (P < 0.05). Also, more cases achieve both-endplates-touching of cement in group A (P < 0.05). And there are less of the loss of vertebral height, KA, and occurrence of re-collapse of the vertebra in group A during the follow-up (P < 0.05). Conclusion: PKP assisted with MR technology can accurately orientate the position of IVC area, which can be augmented by the balloon leading to more satisfied vertebral height improvement, cement diffusion, and pain relief. Trial registration: ClinicalTrials.gov Identifier: NCT03959059. Registered 25 September 2016. [ABSTRACT FROM AUTHOR]