Extracorporeal Membrane Oxygenation in Septic Cardiomyopathy Caused by Aspergillus Infection: The First Case Report.

Septic cardiomyopathy (SCM) is often associated with bacterial infections but also occurs with infections with viruses such as influenza and spirochetes, including syphilis. However, there has been no systematic investigation into whether Aspergillus infections can cause septic cardiomyopathy. We report on such a case for the first time in a patient without immunodeficiency. Therefore, clinicians should be concerned with septic cardiomyopathy caused by some atypical or rare pathogens when admitting such patients.

The incidence and impact of atrial fibrillation on hospitalized Coronavirus disease-2019 patients.

BACKGROUND: Since 2019, Coronavirus disease-2019 (COVID-19) has raised unprecedented global health crisis. The incidence and impact of atrial fibrillation (AF) on patients with COVID-19 remain unclearly defined. METHODS: We conducted a retrospective cohort study using ICD-10 codes to identify patients with a primary diagnosis of COVID-19 with or without AF in National Inpatient Sample Database 2020. We compared the outcome of COVID-19 patients with a concurrent diagnosis of AF with those without. HYPOTHESIS: AF will adversely affect the prognosis of hospitalized COVID-19 patients. RESULTS: A total of 211 619 patients with a primary diagnosis of COVID-19 were identified. Among these patients, 31 923 (15.08%) had a secondary diagnosis of AF. Before propensity score matching, COVID-AF cohort was older (75.8 vs. 62.2-year-old, p < .001) and had more men (57.5% vs. 52.0%, p < .001). It is associated with more comorbidities, mainly including diabetes mellitus (43.7% vs. 39.9%, p < .001), hyperlipidemia (54.6% vs. 39.8%, p < .001), chronic kidney disease (34.5% vs. 17.0%, p < .001), coronary artery disease (35.3% vs. 14.4%, p < .001), anemia (27.8% vs. 18.6%, p < .001), and cancer (4.8% vs. 3.4%, p < .001). After performing propensity score match, a total of 31 862 patients were matched within each group. COVID-AF cohort had higher inpatient mortality (22.2% vs. 15.3%, p < .001) and more complications, mainly including cardiac arrest (3.9% vs. 2.3%, p < .001), cardiogenic shock (0.9% vs. 0.3%, p < .001), hemorrhagic stroke (0.4% vs. 0.3%, p = .025), and ischemic stroke (1.3% vs. 0.7%, p < .001). COVID-AF cohort was more costly, with a longer length of stay, and a higher total charge. CONCLUSION: AF is common in patients hospitalized for COVID-19, and is associated with poorer in-hospital mortality, immediate complications and increased healthcare resource utilization.

Bone regeneration with hydroxyapatite particles loaded in photo-cross-linkable hydrogel: An experimental study.

This study explores the use of in situ cross-linked hyaluronic acid methacryloyl (HAMA) and hydroxyapatite particles (HAP) for bone defect repair. Human periodontal ligament stem cells (PDLSCs) were isolated and co-cultured with the HAMA-HAP composite. Osteogenic differentiation was evaluated using Alizarin Red staining, alkaline phosphatase activity quantification, and polymerase chain reaction (PCR). A cranial defect was induced in Sprague-Dawley rats. This defect was then filled with the HAMA-HAP composite and cross-linked using UV light exposure. Bone formation was assessed through radiographic and histological analyses. The HAMA-HAP composite was found to promote cell viability similarly to pure HAP. It also enhanced gene expression of ALP, OPN, and Runx2, and increased ALP activity and mineralized nodule formation in vitro. Micro-CT scans showed defect restoration in the HAMA-HAP and HAP groups compared to the control group. The HAMA-HAP group exhibited higher Tb.N, Tb.Sp, Tb.Th, and BV/TV. Masson staining showed the HAMA-HAP composite restored the defect site, with new bone formation thicker than in the HAP group. The HAMA-HAP composite showed excellent biocompatibility and promoted osteogenic differentiation of PDLSCs. It effectively repaired cranial defects, indicating its potential for clinical use in bone defect repair.

A Case Report of Streptococcus Dysgalactiae Toxic Shock Syndrome Complicated with Symmetric Peripheral Gangrene.

Streptococcus dysgalactiae subspecies equlsimilis (SDSE) is considered an important bacterial pathogen, and attention has also increased with the increasing number of invasive SDSE infections. Here, we report a patient with S. dysgalactiae toxic shock syndrome complicated by symmetrical peripheral gangrene (SPG). Despite surviving active treatment, amputation severely impacts the quality of life of patients. Therefore, we should pay attention to the early treatment of SDSE infection and the prevention and treatment of related complications.

Risk factors for progression to bacteremia among patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia in the Intensive Care Unit.

Antibiotic-resistant Acinetobacter baumannii (A. baumannii) is a common cause of hospital-acquired infections. This study aimed to identify independent factors associated with progression from nosocomial pneumonia to bacteremia in patients infected with carbapenem-resistant A. baumannii (CR-AB). From 2019 to 2021, we conducted a retrospective anaylsis of the medical records of 159 nosocomial CR-AB pneumonia patients in our Intensive Care Unit (ICU). We employed both univariate and multivariable logistic regression models to identify factors associated with the progression of nosocomial CR-AB pneumonia to bacteremia. Among the 159 patients with nosocomial CR-AB pneumonia, 40 experienced progression to bacteremia and 38 died within 28 days following diagnosis. Patients who developed bacteremia had a significantly higher 28-day mortality rate compared to those without bloodstream infection (47.50% vs. 15.97%). Multivariable logistic regression revealed that higher levels of C-Reactive protein (CRP) (OR = 1.01) and the use of continuous veno-venous hemofiltration (CVVH) treatment (OR = 2.93) were independently associated with an elevated risk of developing bacteremia. Among patients who developed bloodstream infection, those who died within 28 days exhibited significantly higher level of interleukin-6 (IL-6), a greater frequency of antifungal drugs usage, and a longer duration of machanical ventilation compared to survivors. Furthermore, the use of antifungal drugs was the only factor that associated with 28-day mortality (OR = 4.70). In ICU patients with central venous catheters who have CR-AB pneumonia and are on mechanical ventilation, higher CRP levels and CVVH treatment are risk factors for developing bacteremia. Among patients with bacteremia, the use of antifungal drugs is associated with 28-day mortality.

Video game addiction in psychiatric adolescent population: A hospital-based study on the role of individualism from South China.

BACKGROUND: For decades, video game-related behaviors have been investigated in different psychologic research, much of whose attention has been paid to video game addiction (VGA), while the differences between VGA and social media addiction (SMA) should have deserved more attention. In addition to detecting common risk factors of VGA, one core question is whether social inclination (individualism or collectivism) matters. OBJECT: The objectives of this study were to clarify the prevalence of VGA and SMA,, identify the influencing factors of VGA, and clarify the relationships between VGA and adolescents' individualism-collectivism inclination. METHOD: The survey was conducted among 110 adolescent psychiatric patients. For each interviewee, psychological scales were filled face to face. Path analysis was used to examine the causation structure of the childhood trauma-related symptoms. RESULT: The prevalence of VGA was 40.9% (45 out of 110), and it was 41.8% for SMA (46 out of 110); childhood trauma, social media addiction, the individualistic inclination, and the rate of homosexuality were observed to be independent indicators for video game addiction (r2  = 0.46). CONCLUSION: Psychological counseling on patients' internet-related behaviors may focus on the individualistic personality and possible childhood trauma, which are two important risk factors of video game addiction. It is recommended to distinguish between video game addiction and social addiction in clinical practice.

Hsa_Circ_0005044 Promotes Osteo/Odontogenic Differentiation of Dental Pulp Stem Cell Via Modulating miR-296-3p/FOSL1.

Circular RNAs (circRNAs) are a form of RNAs that lack coding potential. The role of such circRNAs in dental pulp stem cell (DPSC) osteo/odontogenic differentiation remains to be determined. In this study, circRNA expression profiles in DPSC osteo/odontogenic differentiation process were analyzed by RNA-seq. qRT-PCR was used to confirm the differential expression of circ_0005044, miR-296-3p, and FOSL1 in DPSC osteogenic differentiation process. Circ_0005044, miR-296-3p, and FOSL1 were knocked down or overexpressed. Osteoblastic activity and associated mineral activity were monitored via alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Interactions between miR-296-3p, circ_0005044, and FOSL1 were assessed through luciferase reporter assays. Finally, an in vivo system was used to confirm the relevance of circ_0005044 to osteoblastic differentiation. As results, we detected significant circ_0005044 and FOSL1 upregulation in DPSC osteo/odontogenic differentiation process, as well as concomitant miR-296-3p downregulation. When knocking down circ_0005044 or overexpressed miR-296-3p, this significantly inhibited osteogenesis. Luciferase reporter assay confirmed that miR-296-3p was capable of binding to conserved sequences in the wild-type forms of both the circ_0005044 and FOSL1. Furthermore, knocking down circ_0005044 in vivo significantly attenuated bone formation. Therefore, the circ_0005044/miR-2964-3p/FOSL1 axis regulates DPSC osteo/odontogenic differentiation, which may provide potential molecular targets for dental-pulp complex regeneration.

Highly selective NH3 gas sensor based on Co(OH)2/Ti3C2T x nanocomposites operating at room temperature.

Ammonia (NH3) is a common air pollutant and is a biomarker for kidney disease. Therefore, the preparation of ammonia gas sensors with high sensitivity, good selectivity and low operating temperature is of great importance for health protection. Using the in situ electrostatic self-assembly approach, a chemoresistive gas sensor based on Co(OH)2/Ti3C2T x hybrid material was created in this study. The prepared samples were characterized by XRD, XPS, TEM, BET and other testing methods for structure, surface topography and elements. These samples were fabricated into sensors, and the gas sensing properties of the materials were investigated under different test conditions. The results show that the gas response value of the C/M-2 sensor is up to about 14.7%/100 ppm, which is three times the response value of the sensor made of pure MXene to NH3. In addition, the Co(OH)2/Ti3C2T x hybrid sensors exhibit excellent repeatability, high sensitivity under low concentration (less than 5 ppm), fast response/recovery time (29 s/49 s) and long-time stability, which indicates their promising utility in the IoT field.

Prognostic Value and Immune-Infiltration Pattern of KIF4A in Patients with Endometrial Carcinoma.

BACKGROUND: With the development of sequencing technology, an increasing number of biomarkers has been identified in endometrial carcinoma (EC). However, there have been few comprehensive analyses of the KIF4A gene in patients with EC. METHODS: Based on raw data in public databases, the KIF4A gene and protein expression in EC were validated. Logistic regression analysis was conducted to analyze the correlations between clinical characteristics and the KIF4A expression. Kaplan-Meier analysis was used to explore the difference in survival in clinical subgroups. Meanwhile, we used meta-analysis in multiple datasets to investigate the prognostic value of KIF4A. In addition, Cox regression analysis was used to confirm the independent prognostic value of KIF4A, and we constructed a nomogram based on KIF4A expression. Subsequently, we used ESTIMATE and ssGSEA algorithms to excavate the correlation between KIF4A, tumour-infiltrating immune cells, and related gene markers of immune cells. Moreover, the potential biological functions of KIF4A were investigated by gene function annotation. Finally, we identified the hub genes interacting with KIF4A by constructing a protein-protein interaction (PPI) network and screening differential genes (DEGs). RESULTS: In the pan-cancer analysis, KIF4A was upregulated in most tumors (21/33). Similarly, the overexpression of KIF4A in EC patients was confirmed in the TCGA cohort, the GEO cohort, and immunohistochemistry. In addition, upregulated KIF4A is associated with age, survival status, grade, FIGO stage, histological type, tumour invasion, and TCGA molecular subtypes (p < 0.05). KIF4A overexpression was correlated with the grade, histological type, and pathological stage according to logistic regression analysis (p < 0.05). Meanwhile, survival analysis and meta-analysis revealed that KIF4A was associated with a poor prognosis and acted as an independent prognostic marker in EC patients (p < 0.05). KIF4A is associated to immune response and may have a function in controlling immune cell infiltration in EC (20/24, p < 0.05). This is noteworthy given that gene enrichment analysis suggested KIF4A may be involved in the neuroactive ligand-receptor interaction pathway, etc. Finally, we identified transcription factors which have a potential interaction with KIF4A. CONCLUSION: We provided robust evidences that KIF4A is an indicator of poor prognosis and a potential target for immunotherapy in patients with EC.

FMO3-TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population.

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.

Identification of Potential Genetic Biomarkers and Target Genes of Peri-Implantitis Using Bioinformatics Tools.

OBJECTIVES: To investigate potential genetic biomarkers of peri-implantitis and target genes for the therapy of peri-implantitis by bioinformatics analysis of publicly available data. METHODS: The GSE33774 microarray dataset was downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between peri-implantitis and healthy gingival tissues were identified using the GEO2R tool. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database and the Metascape tool, and the results were expressed as a bubble diagram. The protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized using Cytoscape. The hub genes were screened by the cytoHubba plugin of Cytoscape. The potential target genes associated with peri-implantitis were obtained from the DisGeNET database and the Open Targets Platform. The intersecting genes were identified using the Venn diagram web tool. RESULTS: Between the peri-implantitis group and the healthy group, 205 DEGs were investigated including 140 upregulated genes and 65 downregulated genes. These DEGs were mainly enriched in functions such as the immune response, inflammatory response, cell adhesion, receptor activity, and protease binding. The results of KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the cytokine-cytokine receptor interaction, pathways in cancer, and the PI3K-Akt signaling pathway. The intersecting genes, including IL6, TLR4, FN1, IL1ß, CXCL8, MMP9, and SPP1, were revealed as potential genetic biomarkers and target genes of peri-implantitis. CONCLUSIONS: This study provides supportive evidence that IL6, TLR4, FN1, IL1ß, CXCL8, MMP9, and SPP1 might be used as potential target biomarkers for peri-implantitis which may provide further therapeutic potentials for peri-implantitis.

Prognostic Value of Elevated Levels of Plasma N-Acetylneuraminic Acid in Patients With Heart Failure.

BACKGROUND: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring. METHODS: We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF. RESULTS: Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67-2.66], P<0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction. CONCLUSIONS: This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.

Identification of uterine leiomyosarcoma-associated hub genes and immune cell infiltration pattern using weighted co-expression network analysis and CIBERSORT algorithm.

BACKGROUND: While large-scale genomic analyses symbolize a precious attempt to decipher the molecular foundation of uterine leiomyosarcoma (ULMS), bioinformatics results associated with the occurrence of ULMS based totally on WGCNA and CIBERSORT have not yet been reported. This study aimed to screen the hub genes and the immune cell infiltration pattern in ULMS by bioinformatics methods. METHODS: Firstly, the GSE67463 dataset, including 25 ULMS tissues and 29 normal myometrium (NL) tissues, was downloaded from the public database. The differentially expressed genes (DEGs) were screened by the 'limma' package and hub modules were identified by weighted gene co-expression network analysis (WGCNA). Subsequently, gene function annotations were performed to investigate the biological role of the genes from the intersection of two groups (hub module and DEGs). The above genes were calculated in the protein-protein interaction (PPI) network to select the hub genes further. The hub genes were validated using external data (GSE764 and GSE68295). In addition, the differential immune cell infiltration between UL and ULMS tissues was investigated using the CIBERSORT algorithm. Finally, we used western blot to preliminarily detect the hub genes in cell lines. RESULTS: WGCNA analysis revealed a green-yellow module possessed the highest correlation with ULMS, including 1063 genes. A total of 172 DEGs were selected by thresholds set in the 'limma' package. The above two groups of genes were intersected to obtain 72 genes for functional annotation analysis. Interestingly, it indicated that 72 genes were mainly involved in immune processes and the Neddylation pathway. We found a higher infiltration of five types of cells (memory B cells, M0-type macrophages, mast cells activated, M1-type macrophages, and T cells follicular helper) in ULMS tissues than NL tissues, while the infiltration of two types of cells (NK cells activated and mast cells resting) was lower than in NL tissues. In addition, a total of five genes (KDR, CCL21, SELP, DPT, and DCN) were identified as the hub genes. Internal and external validation demonstrated that the five genes were over-expressed in NL tissues compared with USML tissues. Finally, the correlation analysis results indicate that NK cells activated and mast cells activated positively correlated with the hub genes. However, M1-type macrophages had a negative correlation with the hub genes. Moreover, only the DCN may be associated with the Neddylation pathway. CONCLUSION: A series of evidence confirm that the five hub genes and the infiltration of seven types of immune cells are related to USML occurrence. These hub genes may affect the occurrence of USML through immune-related and Neddylation pathways, providing molecular evidence for the treatment of USML in the future.

Bi-allelic BRWD1 variants cause male infertility with asthenoteratozoospermia and likely primary ciliary dyskinesia.

Genetics-associated asthenoteratozoospermia is often seen in patients with multiple morphological abnormalities of the sperm flagella (MMAF). Although 24 causative genes have been identified, these explain only approximately half of patients with MMAF. Since sperm flagella and motile cilia (especially respiratory cilia) have similar axonemal structures, many patients with MMAF also exhibit respiratory symptoms, such as recurrent airway infection, chronic sinusitis, and bronchiectasis, which are frequently associated with primary ciliary dyskinesia (PCD), another recessive disorder. Here, exome sequencing was conducted to evaluate the genetic cause in 53 patients with MMAF and classic PCD/PCD-like symptoms. Two homozygous missense variants and a compound-heterozygous variant in the BRWD1 gene were identified in three unrelated individuals. BRWD1 staining was detected in the whole flagella and respiratory cilia of normal controls but was absent in BRWD1-mutated individuals. Transmission electron microscopy and immunostaining demonstrated that BRWD1 deficiency in human affected respiratory cilia and sperm flagella differently, as the absence of outer and inner dynein arms in sperm flagellum and respiratory cilia, while with a decreased number and outer doublet microtubule defects of respiratory cilia. To our knowledge, this is the first report of a BRWD1-variant-related disease in humans, manifesting as an autosomal recessive form of MMAF and PCD/PCD-like symptoms. Our data provide a basis for further exploring the molecular mechanism of BRWD1 gene during spermatogenesis and ciliogenesis.

Progressive osseous heteroplasia: a case report and literature review.

OBJECTIVE: To investigate the clinical features and pathogenesis of progressive osseous heteroplasia (POH) in children. METHODS: The clinical features and imaging findings of a child with POH are described, and family investigations and gene comparisons were performed, followed by a literature review. RESULTS: A 9-year-old female with no relevant family medical history initially presented with ectopic ossification of the skin and subcutaneous tissue of the right face that developed slowly. The ossification area extended to the right waist, back, and right knee. The unilateral body (limbs) was gradually invaded. The patient exhibited limited movement of the head, neck, and left shoulder joint, and experienced difficulty in opening her mouth. She also exhibited deformity of the toe, delayed development, insufficient language skills and behavioral ability, and difficulty in communicating with others, but had no apparent endocrine disorders. Blood calcium, phosphorus, and alkaline phosphatase levels were normal, and DNA sequencing did not yield a positive result. CONCLUSION: The clinical manifestations of POH include hard plaques, which can develop deep into the bone; however, there are currently no effective preventive or treatment measures.

Hydroxyapatite-incorporation improves bone formation on endosseous PEEK implant in canine tibia.

BACKGROUND: Poly Ether Ether Ketone (PEEK) has been considered as a potential alternative material for endosseous dental implants, for its low elastic modulus, biocompatibility, and low cost in customized device manufacture. Hydroxyapatite-incorporation is supposed to improve the poor osseointegration of PEEK. METHODS: In the present study we analyzed the in vivo response of hydroxyapatite-incorporated PEEK (PEEK-HA) implants in canine tibia. PEEK-HA and PEEK implants were implanted and were examined 4 weeks and 12 weeks after implantation with radiology and histology. Commercial titanium dental implants served as controls. RESULTS: The ratio of bone volume to tissue volume of PEEK-HA implants was higher than that of PEEK implants 4 weeks after implantation in the µ-CT analysis. The bone implant contact of PEEK and PEEK-HA implants showed no statistical difference in the histological examination, but newly-formed bone around PEEK-HA implants showed more signs of mineralization than that around PEEK implants. CONCLUSION: The study suggested that bone formation was improved with hydroxyapatite-incorporation in PEEK. Hydroxyapatite-incorporated PEEK implants may represent a potential material for endosseous dental implant.

CDK9 inhibitor CDKI-73 is synergetic lethal with PARP inhibitor olaparib in BRCA1 wide-type ovarian cancer.

Poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors benefit a small percentage of ovarian cancer patients with homologous recombination (HR) deficiency (HRD), which greatly limits the applications of PARP inhibitors. Given the function of CDK9 in homologous recombination repair (HRR), here, we show how to extend the utility of PARP inhibitors in BRCA1-proficient ovarian cancer by targeting CDK9. We found that high CDK9 expression is associated with a higher tumor stage in epithelial ovarian cancer patients, and CDK9 is co-expressed with BRCA1 by analyzing a public database. By using a CDK9 inhibitor CDKI-73, we found that its combination with the PARP inhibitor olaparib significantly suppressed cell viability and colony formation and induced apoptosis in BRCA1-proficient ovarian cancer cells. Consistently, the combination treatment remarkably reduced the tumor growth in mouse xenograft models. We demonstrated that CDKI-73 could downregulate BRCA1 expression, resulting in hypersensitivity to olaparib in BRCA1-proficient ovarian cancer. Taken together, our results show a synergetic effect of CDKI-73 combined with olaparib in BRCA1-proficient ovarian cancer, facilitating the clinical use of CDK9 as a predictive biomarker to exploit PARP inhibitors.

Depletion of UBE2C reduces ovarian cancer malignancy and reverses cisplatin resistance via downregulating CDK1.

Ovarian cancer is the most lethal gynecological malignancy, but the mechanisms of ovarian cancer progression and cisplatin resistance remain unclear. Emerging evidence suggested that ubiquitin-conjugating enzyme E2C (UBE2C) was highly expressed in a variety of tumors and acted as an oncogene. In our study, we demonstrated that UBE2C was overexpressed in ovarian cancer by immunohistochemistry (IHC) and The Cancer Genome Atlas (TCGA) database analysis. It was also found that high levels of UBE2C expression predicted worse clinical outcomes in ovarian cancer. After knocking down UBE2C, SKOV3 and A2780 cells showed inhibitory cell proliferation, increased apoptosis by blocking G2/M transition in vitro and in vivo. Besides, the downregulation of UBE2C reversed the cisplatin resistance states of SKOV3/DDP and A2780/DDP cells. Interestingly, CDK1 expression was also downregulated in UBE2C depleted ovarian cancer cells. Furthermore, we found that UBE2C expression was highly correlated with CDK1 expression in ovarian cancer tissues and cell lines, indicating that UBE2C might cooperate with CDK1 in ovarian tumorigenesis. Collectively, our findings strongly supported UBE2C as a candidate oncogene and a potential target for the treatment of ovarian cancer.

Clinical outcomes after ticagrelor and clopidogrel in Chinese post-stented patients.

BACKGROUND AND AIMS: International guidelines recommend ticagrelor over clopidogrel as preferred antiplatelet agent in patients following coronary stenting. However, no large real-life evidence is available in East Asians in general, and Chinese in particular, with regard to associated clinical outcomes. The present study aimed to assess the early and delayed outcomes after ticagrelor versus clopidogrel in post stenting Chinese patients. METHODS: We conducted the pre-specified interim analysis of Comparison Of Efficacy and Safety Between TIcagrelor and Clopidogrel In Chinese (COSTIC), the ongoing prospective, observational, single-center trial. Primary outcomes include first occurrence of myocardial infarction, stroke, vascular death and Bleeding Academic Research Consortium (BARC) scale bleeding event. Propensity score matching (PSM) was carried out to adjust for differences in baseline characteristics between treatment arms. RESULTS: In total, 4,465 patients were enrolled. After PSM, the patients prescribed with ticagrelor had a lower incidence of primary efficacy endpoint relative to those with clopidogrel (0.6% vs. 1.4%, HR = 0.44, 95%CI: 0.22-0.89, p = 0.019) at 1 month, but similar at 7 days, 6 months and 12 months. Further analysis indicated that the difference only exists in the subgroup of acute myocardial infarction (AMI) patients. With regard to safety, ticagrelor consistently increased the risk of BARC type 2 bleeding compared to clopidogrel at 1 month, 6 months and 12 months. CONCLUSIONS: These preliminary data indicate that ticagrelor is superior to clopidogrel with regard to major vascular thrombotic outcomes at 1 month, especially in the AMI population, but both groups are similar at 7 days, 6 months and 12 months. Ticagrelor consistently caused significantly more BARC type 2 bleeding.

LAPTM5 is transactivated by RUNX2 and involved in RANKL trafficking in osteoblastic cells.

The present study aimed to investigate the role of lysosomal­associated transmembrane protein 5 (LAPTM5) in osteoclast differentiation induced by osteoblasts. The results demonstrated that the expression levels of LAPTM5 were downregulated following runt­related transcription factor 2 (RUNX2) silencing and upregulated following RUNX2 overexpression in ST2 cells. Chromatin immunoprecipitation analysis identified the binding of RUNX2 to the LAPTM5 promoter at the ­1176 to ­1171 position. Dual­luciferase reporter assays confirmed that RUNX2 directly activated the LAPTM5 gene. The concentration of receptor activator of nuclear factor­κB ligand (RANKL) protein in the cytoplasm and in the media was significantly increased following LAPTM5 knockdown. LAPTM5 silencing in ST2 cells enhanced osteoclastic differentiation of co­cultured RAW264.7 cells. The present study indicated that expression of LAPTM5 was regulated by the interaction of RUNX2 with its promoter region and that LAPTM5 was involved in the trafficking of RANKL. These findings suggested a possible coupling mechanism between osteogenesis and osteoclastogenesis in which RUNX2 may be involved in osteoclast differentiation through the regulation of the lysosome­associated genes that modulate RANKL expression.