m6A-dependent upregulation of DDX21 by super-enhancer-driven IGF2BP2 and IGF2BP3 facilitates progression of acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is a haematological malignancy with unfavourable prognosis. Despite the effectiveness of chemotherapy and targeted therapy, relapse or drug resistance remains a major threat to AML patients. N6-methyladenosine (m6A) RNA methylation and super-enhancers (SEs) are extensively involved in the leukaemogenesis of AML. However, the potential relationship between m6A and SEs in AML has not been elaborated. METHODS: Chromatin immunoprecipitation (ChIP) sequencing data from Gene Expression Omnibus (GEO) cohort were analysed to search SE-related genes. The mechanisms of m6 A-binding proteins IGF2BP2 and IGF2BP3 on DDX21 were explored via methylated RNA immunoprecipitation (MeRIP) assays, RNA immunoprecipitation (RIP) assays and luciferase reporter assays. Then we elucidated the roles of DDX21 in AML through functional assays in vitro and in vivo. Finally, co-immunoprecipitation (Co-IP) assays, RNA sequencing and ChIP assays were performed to investigate the downstream mechanisms of DDX21. RESULTS: We identified two SE-associated transcripts IGF2BP2 and IGF2BP3 in AML. High enrichment of H3K27ac, H3K4me1 and BRD4 was observed in IGF2BP2 and IGF2BP3, whose expression were driven by SE machinery. Then IGF2BP2 and IGF2BP3 enhanced the stability of DDX21 mRNA in an m6A-dependent manner. DDX21 was highly expressed in AML patients, which indicated a poor survival. Functionally, knockdown of DDX21 inhibited cell proliferation, promoted cell apoptosis and led to cell cycle arrest. Mechanistically, DDX21 recruited transcription factor YBX1 to cooperatively trigger ULK1 expression. Moreover, silencing of ULK1 could reverse the promoting effects of DDX21 overexpression in AML cells. CONCLUSIONS: Dysregulation of SE-IGF2BP2/IGF2BP3-DDX21 axis facilitated the progression of AML. Our findings provide new insights into the link between SEs and m6A modification, elucidate the regulatory mechanisms of IGF2BP2 and IGF2BP3 on DDX21, and reveal the underlying roles of DDX21 in AML.

A comprehensive review of oxygen vacancy modified photocatalysts: synthesis, characterization, and applications.

Photocatalytic technology is a novel approach that harnesses solar energy for efficient energy conversion and effective pollution abatement, representing a rapidly advancing field in recent years. The development and synthesis of high-performance semiconductor photocatalysts constitute the pivotal focal point. Oxygen vacancies, being intrinsic defects commonly found in metal oxides, are extensively present within the lattice of semiconductor photocatalytic materials exhibiting non-stoichiometric ratios. Consequently, they have garnered significant attention in the field of photocatalysis as an exceptionally effective means for modulating the performance of photocatalysts. This paper provides a comprehensive review on the concept, preparation, and characterization methods of oxygen vacancies, along with their diverse applications in nitrogen fixation, solar water splitting, CO2 photoreduction, pollutant degradation, and biomedicine. Currently, remarkable progress has been made in the synthesis of high-performance oxygen vacancy photocatalysts and the regulation of their catalytic performance. In the future, it will be imperative to develop more advanced in situ characterization techniques, conduct further investigations into the regulation and stabilization of oxygen vacancies in photocatalysts, and comprehensively comprehend the mechanism underlying the influence of oxygen vacancies on photocatalysis. The engineering of oxygen vacancies will assume a pivotal role in the realm of semiconductor photocatalysis.

RAB10 promotes breast cancer proliferation migration and invasion predicting a poor prognosis for breast cancer.

RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. Our findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

circSLC25A13 acts as a ceRNA to regulate AML progression via miR-616-3p/ADCY2 axis.

Circular RNAs (circRNAs), a type of endogenous noncoding RNA (ncRNA), exert vital roles in leukemia progression and are promising prognostic factors. Here, we report a novel circRNA, circSLC25A13 (hsa_circ_0081188), which was increased in acute myeloid leukemia (AML) patients with poor overall survival (OS) comparing to patients with good prognosis. Knockdown of circSLC25A13 in AML cells inhibited proliferation and increased cell apoptosis in vitro and in vivo. Enhanced circSLC25A13 expression promoted the survival of AML cells. Mechanistically, circSLC25A13 played as a microRNA sponge of miR-616-3p, which inhibited the expression of adenylate cyclase 2 (ADCY2). Downregulation of miR-616-3p and overexpression of ADCY2 partially rescued circSLC25A13 deficient induced cell growth arrest. In summary, through competitive absorption of miR-616-3p and thereby upregulating ADCY2 expression, circSLC25A13 promoted AML progression. Moreover, circSLC25A13 may represent a potential novel biomarker for the prognosis of AML and offer a potential therapeutic target for AML treatment.

Dyslipidemia in diffuse large B-cell lymphoma based on the genetic subtypes: a single-center study of 259 Chinese patients.

Background: Diffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes. Results: This study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p <0.001) is higher in the EZB subtype than in others, especially hypertriglyceridemia (78.3%, p = 0.001) in the EZB subtype. Based on the pathological gene-sequencing, patients with BCL2 gene fusion mutation are significantly correlative with hyperlipidemia (76.5%, p = 0.006) and hypertriglyceridemia (88.2%, p = 0.002). Nevertheless, the occurrence of dyslipidemia has no remarkable influence on prognosis. Conclusion: In summary, dyslipidemia correlates with genetic heterogeneity in DLBCL without having a significant influence on survival. This research first connects lipids and genetic subtypes in DLBCL.

Conditioned medium of human menstrual blood-derived endometrial stem cells protects against cell inflammation and apoptosis of Npc1KO N2a cells.

Niemann-Pick disease type C1 (NPC1) is a hereditary neurodegenerative disorder caused by a mutation in the NPC1 gene. This gene encodes a transmembrane protein found in lysosomes. This disease characterized by hepatosplenomegaly, neurological impairments and premature death. Recent preclinical studies have shown promising results in using mesenchymal stem cells (MSCs) to alleviate the symptoms of NPC1. One type of MSCs, known as human menstrual blood-derived endometrial stem cells (MenSCs), has attracted attention due to its accessibility, abundant supply, and strong proliferation and regeneration capabilities. However, it remains uncertain whether the conditioned medium of MenSCs (MenSCs-CM) can effectively relieve the symptoms of NPC1. To investigate this further, we employed the CRISPR-Cas9 technique to successfully create a Npc1 gene knockout N2a cell line (Npc1KO N2a). Sanger sequencing confirmed the occurrence of Npc1 gene mutation in these cells, while western blotting revealed a lack of NPC1 protein expression. Filipin staining provided visual evidence of unesterified cholesterol accumulation in Npc1KO N2a cells. Moreover, Npc1KO N2a cells exhibited significantly decreased viability, increased inflammation, and heightened cell apoptosis. Notably, our study demonstrated that the viability of Npc1KO N2a cells was most significantly improved after being cultured by 36 h-collected MenSCs-CM for 0.5 days. Additionally, MenSCs-CM exhibited the ability to effectively reduce inflammation, counteract cell apoptosis, and ameliorate unesterified cholesterol accumulation in Npc1KO N2a cells. This groundbreaking finding establishes, for the first time, the protective effect of MenSCs-CM on N2a cells with Npc1 gene deletion. These findings suggest that the potential of MenSCs-CM as a beneficial therapeutic approach for NPC1 and other neurodegenerative diseases.

LncRNA MAGI2-AS3-Encoded Polypeptide Restrains the Proliferation and Migration of Breast Cancer Cells.

Accumulating articles have reported the coding potential of long non-coding RNAs (lncRNAs). However, only a few lncRNAs-encoded peptides have been studied. Breast cancer (BRCA) progression-related gene modules were determined by weighted gene co-expression network analysis (WGCNA). Cell viability, proliferation, and migration capacities were assessed by Cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays. Immunofluorescence (IF) assay was implemented to observe protein expression. Co-immunoprecipitation (Co-IP) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) were employed to analyze MAGI2 antisense RNA 3 (MAGI2-AS3)-ORF5-interacted proteins. WGCNA identified that MEpurple and MEblack modules were significantly negatively correlated with T stage in BRCA patients. MAGI2-AS3 was screened as one of the differentially expressed (DE) lncRNAs with translational potential in MEblack and MEpurple modules in BRCA. The data in The Cancer Genome Atlas (TCGA) uncovered that MAGI2-AS3 abundance was significantly decreased in invasive BRCA patients, and it had high diagnostic and prognostic values. MAGI2-AS3-ORF5 notably restrained BRCA cell viability, proliferation, and migration. Mechanically, MAGI2-AS3-ORF5 might affect the progression of BRCA cells by binding to extracellular matrix (ECM)-related proteins. MAGI2-AS3-ORF5 played an anti-tumor role by inhibiting BRCA cell viability, proliferation, and migration. MAGI2-AS3-ORF5 might modulate BRCA cell migration through ECM-associated proteins.

Effects of Cu and Ag Elements on Corrosion Resistance of Dual-Phase Fe-Based Medium-Entropy Alloys.

The effect of adding elements to promote phase separation on the functional properties of medium-entropy alloys has rarely been reported. In this paper, medium-entropy alloys with dual FCC phases were prepared by adding Cu and Ag elements, which exhibited a positive mixing enthalpy with Fe. Dual-phase Fe-based medium-entropy alloys were fabricated via water-cooled copper crucible magnetic levitation melting and copper mold suction casting. The effects of Cu and Ag elements microalloying on the microstructure and corrosion resistance of a medium-entropy alloy were studied, and an optimal composition was defined. The results show that Cu and Ag elements were enriched between the dendrites and precipitated an FCC2 phase on the FCC1 matrix. During electrochemical corrosion under PBS solutions, Cu and Ag elements formed an oxide layer on the alloy's surface, which prevented the matrix atoms from diffusing. With an increase in Cu and Ag content, the corrosion potential and the arc radius of capacitive resistance increased, while the corrosion current density decreased, indicating that corrosion resistance improved. The corrosion current density of (Fe63.3Mn14Si9.1Cr9.8C3.8)94Cu3Ag3 in PBS solution was as high as 1.357 × 10-8 A·cm-2.

The Efficacy of Scouting Technology in Pedicle Screw Placement in the Patients With Degenerative Scoliosis.

Objective: To investigate the curative effect of ball tip technology in pedicle screw placement in the patients with degenerative scoliosis (DS), as compared to traditional freehand technique. Methods: A total of 90 patients with degenerative scoliosis who were admitted to Affiliated Hospital of Hebei Engineering University from October 2019 to October 2021 were selected as the objects in this prospective study. They were randomly divided into an experimental group and a control group with 45 cases in each. The clinical indications, the accuracy of pedicle screw placement, the occurrence of surgical complications, the measurement of spinal and pelvic parameters, the recovery of spinal function and pain degree were recorded and compared within the two groups. Results: After treatment, the operation time, intraoperative blood loss, total number of screws, and time of screwing were compared between the two groups, and the difference was not significant (P > .05). However, the bedding time and the hospital stay were shorter in the experimental group than the control group with difference (P < .05). There was no significant difference in clinical standards and poor implantation in the Gertzbein-Robbins A-E classification between the two groups (P > .05). While the number of perfect placement of screws in the experimental group was higher (P < .05). Before treatment, the Cobbs angle and pelvic incidence-lumbar lordosis (PI-LL) levels of the two groups were comparable (P > .05); after treatment, the Cobbs angle and PI-LL levels of the two groups were lower than those before treatment, and the difference was significant (P < .05). There was no significant difference in Cobbs angle and PI-LL levels between groups (P > .05). Before treatment, the JOA and DOI scores of the two groups were comparable (P > .05); after treatment, the JOA and DOI scores of the two groups were improved (P < .05); the improvement of JOA and DOI scores of the experimental group were better than those in the control group (P < .05). Before treatment, there was no significant difference in the pain degree between the two groups (P > .05); after treatment, the pain of the two groups was improved compared with that before treatment, and the pain degree of the experimental group was lower than that of the control group (P < .05). The incidence of postoperative complications in the experimental group was lower than that in the control group, but there was no significant difference in the total incidence of postoperative complications between the two groups (P > .05). Conclusion: The scouting technique-assisted screw placement can effectively improve the spinal function of patients with degenerative scoliosis, with obvious curative effect and high safety.

FLOT1 knockdown inhibits growth of AML cells through triggering apoptosis and pyroptosis.

Acute myeloid leukemia (AML) is a group of hematological malignancies characterized by clonal proliferation of immature myeloid cells. Lipid rafts are highly organized membrane subdomains enriched in cholesterol, sphingolipids, and gangliosides and play roles in regulating apoptosis through subcellular redistribution. Flotillin1 (FLOT1) is a component and also a marker of lipid rafts and had been reported to be involved in the progression of cancers and played important roles in cell death. However, the role of FLOT1 in AML remains to be explored. In this study, we found that increased expression of FLOT1 was correlated with poor clinical outcome in AML patients. Knockdown of FLOT1 in AML cells not only promoted cell death in vitro but also inhibited malignant cells engraftment in vivo. Mechanically, FLOT1 knockdown triggered apoptosis and pyroptosis. FLOT1 overexpression promoted AML cell growth and apoptosis resistance. Our findings indicate that FLOT1 is a prognostic factor of AML and may be a potential target for AML treatment.

CRISPR-Cas9-Mediated NPC1 Gene Deletion Enhances HEK 293 T Cell Adhesion by Regulating E-Cadherin.

NPC1 gene encodes a transmembrane glycoprotein on the late endosome/lysosomal membrane. Its mutation leads to a rare and aggravated autosomal recessive neurovisceral condition, termed Niemann-Pick disease type C1 (NPC1), which is characterized by progressive neurodegeneration, visceral symptoms, and premature death. To investigate the influence of NPC1 gene deletion on cell morphology, adhesion, proliferation, and apoptosis, CRISPR-Cas9 technology was used to knockout the NPC1 gene in HEK 293 T cells. Sanger sequencing, western blotting, and immunofluorescence were used to confirm successful NPC1 ablation. Filipin staining results indicated that deletion of NPC1 gene led to accumulation of unesterified cholesterol in HEK 293 T cells. Phalloidin staining results revealed cell aggregation, synapse shortening, nuclear enlargement, and cytoskeleton filamentous actin thinning in HEK 293 T cells with NPC1 gene mutation. Furthermore, NPC1 gene mutated HEK 293 T cell showed enhanced cell adhesion, inhibited cell proliferation, and increased cell apoptosis. In addition, NPC1 gene mutations significantly increased the protein expression levels of E-cadherin and γ-catenin and significantly decreased the protein expression levels of Wnt 3a, c-Myc, and cyclin D1. These results suggest that NPC1 may regulate cell adhesion by affecting the cadherin-catenin complex through E-cadherin, and that the classical Wnt signaling pathway may be inhibited by restricting ß-catenin from entering the nucleus to inhibit cell proliferation.

ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD.

Bromodomain-containing protein 4 (BRD4) inhibitors have been clinically developed to treat acute myeloid leukemia (AML), but their application is limited by the possibility of drug resistance, which is reportedly associated with the activation of the WNT/ß-catenin pathway. Meanwhile, homoharringtonine (HHT), a classic antileukemia drug, possibly inhibits the WNT/ß-catenin pathway. In this study, we attempted to combine a novel BRD4 inhibitor (ACC010) and HHT to explore their synergistic lethal effects in treating AML. Here, we found that co-treatment with ACC010 and HHT synergistically inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive AML cells in vitro, and significantly inhibiting AML progression in vivo. Mechanistically, ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitor-resistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD.

Versatile Medium Entropy Ti-Based Bulk Metallic Glass Composites.

An ultra-strong Ti-based bulk metallic glass composite was developed via the transformation-induced plasticity (TRIP) effect to enhance both the ductility and work-hardening capability of the amorphous matrix. The functionally graded composites with a continuous gradient microstructure were obtained. It was found that the austenitic center possesses good plasticity and toughness. Furthermore, the amorphous surface exhibited high strength and hardness, as well as excellent wear corrosion resistance. Compared with the Ti-6Al-4V alloy, bulk metallic glass composites (BMGCs) exhibit better spontaneous passivation behavior during the potential dynamic polarization. No crystallization was observed on the friction surface, indicating their good friction-reduction and anti-wear properties.

Minimally invasive repair of iatrogenic right ventricular perforation guided by bedside contrast-enhanced ultrasound: A case report and literature review.

This case report involves a 93-year-old female patient with atrioventricular block and suffered right ventricular free wall perforation during installation of Micra Leadless Pacemaker (MLP). Pericardial tamponade occurred shortly, and we adopted pericardial catheter drainage as the primary emergency treatment. Considering the patient's physical conditions and leveraging the special treatment facilitates of the Intensive Care Unit (ICU), we tried a new emergency treatment approach. After putting the patient under intravenous anesthesia (no cardiac arrest), we made a small intercostal incision and performed bedside minimally invasive repair of right ventricular free wall perforation. It should be noted that ultrasound played a key role in pinpointing the breach and intraoperative guidance. We first used contrast-enhanced ultrasound (CEUS) to locate the breach. Then guided by bedside ultrasound, we accessed the perforation with the minimum incision size (5 cm). Our experience in this case may serve as a good reference in the emergency treatment for right ventricular free wall perforation.

Genome-wide identification of calcineurin B-like protein-interacting protein kinase gene family reveals members participating in abiotic stress in the ornamental woody plant Lagerstroemia indica.

Calcineurin B-like protein-interacting protein kinases (CIPKs) play important roles in plant responses to stress. However, their function in the ornamental woody plant Lagerstroemia indica is remains unclear. In this study, the LiCIPK gene family was analyzed at the whole genome level. A total of 37 LiCIPKs, distributed across 17 chromosomes, were identified. Conserved motif analysis indicated that all LiCIPKs possess a protein kinase motif (S_TKc) and C-terminal regulatory motif (NAF), while seven LiCIPKs lack a protein phosphatase interaction (PPI) motif. 3D structure analysis further revealed that the N-terminal and C-terminal 3D-structure of 27 members are situated near to each other, while 4 members have a looser structure, and 6 members lack intact structures. The intra- and interspecies collinearity analysis, synonymous substitution rate (K s ) peaks of duplicated LiCIPKs, revealed that ∼80% of LiCIPKs were retained by the two whole genome duplication (WGD) events that occurred approximately 56.12-61.16 million year ago (MYA) and 16.24-26.34 MYA ago. The promoter of each LiCIPK contains a number of auxin, abscisic acid, gibberellic acid, salicylic acid, and drought, anaerobic, defense, stress, and wound responsive cis-elements. Of the 21 members that were successfully amplified by qPCR, 18 LiCIPKs exhibited different expression patterns under NaCl, mannitol, PEG8000, and ABA treatments. Given that LiCIPK30, the AtSOS2 ortholog, responded to all four types of stress it was selected for functional verification. LiCIPK30 complements the atsos2 phenotype in vivo. 35S:LiCIPK-overexpressing lines exhibit increased leaf area increment, chlorophyll a and b content, reactive oxygen species scavenging enzyme activity, and expression of ABF3 and RD22, while the degree of membrane lipid oxidation decreases under NaCl treatment compared to WT. The evolutionary history, and potential mechanism by which LiCIPK30 may regulate plant tolerance to salt stress were also discussed. In summary, we identified LiCIPK members involved in abiotic stress and found that LiCIPK30 transgenic Arabidopsis exhibits more salt and osmotic stress tolerance than WT. This research provides a theoretical foundation for further investigation into the function of LiCIPKs, and for mining gene resources to facilitate the cultivation and breeding of new L. indica varieties in coastal saline-alkali soil.

Quantitative analysis of heavy metals in soil by X-ray fluorescence with PCA-ANOVA and support vector regression.

Heavy metal concentration is an important index for evaluating soil pollution. It is of great significance to measure the trace element content accurately for green agriculture development. In order to detect the trace element content accurately, a new prediction framework including pre-processing, signal extraction, feature selection and decision-making was proposed. The energy dispersive X-ray fluorescence (ED-XRF) spectra of 57 national standard soil samples were investigated based on the proposed methods. Firstly, an innovative background deduction method called iterative adaptive window empirical wavelet transform (IAWEWT) was introduced to extract effective counts of characteristic peaks, and the proposed approach was validated by the coefficient of determination (R2) of the instrumental calibration curve compared with two other conventional methods. Secondly, principal component analysis (PCA) was combined with the analysis of variance (ANOVA) for variable selection optimization of the ED-XRF spectrum. After PCA feature extraction and ANOVA variable selection treatment, the optimum number of principal components for V, Cr, Cu, Zn, Mo, Cd and Pb were determined to be 7, 15, 4, 4, 4, 5 and 12 respectively. Furthermore, the support vector regression (SVR) model was adopted for heavy metal estimation. The evaluation indices included R2 and root mean square error (RMSE). It was demonstrated that the predictive capabilities of seven heavy metal elements were improved substantially for elemental analysis by the proposed PCA-ANOVA-SVR model, with excellent results for V, Cr, Cu, Zn, Mo, Cd and Pb estimates, and the R2 values were 0.993, 0.996, 0.999, 0.999, 0.997, 0.998 and 0.998 respectively. Therefore, the new framework proposed in this paper can effectively eliminate redundant features and determine the concentration of trace elements in soil. It provides an effective alternative for the quantitative analysis of X-ray fluorescence spectrometry.

Safrole oxide induced 5-HT neuron-like cell differentiation of bone marrow mesenchymal stem cells by elevating G9a.

In our previous study, we found that safrole oxide (SFO) could induce bone marrow mesenchymal stem cell differentiation into neuron-like cells. However, which kind of neuron cells was induced by SFO was unknown. Here, we found that SFO could induce BMSC differentiation into 5-hydroxytryptamine (5-HT) neuron-like cells. Microarray analysis of BMSCs treated with SFO for 6 h revealed a total of 35 genes changed more than twice. We selected G9a, a histone methyltransferase for further study. The upregulation of G9a was confirmed by RT-PCR and Western blot analysis. Small interfering RNA knockdown of G9a blocked SFO-induced BMSC differentiation. These results demonstrated that G9a was the pivotal factor in SFO-medicated 5-HT neuronal differentiation of BMSCs. Our findings provide a new clue for further investigating the gene control of BMSC differentiation into 5-HT neuron-like cells and provide a putative strategy for depression diseases therapies.

Percutaneous ultrasound-guided core needle biopsy for the diagnosis of cardiac tumors: Optimizing the treatment strategy for patients with intermural and pericardial cardiac tumors.

Objective: The aims of this study are to investigate the clinical value and practical safety of ultrasound-guided percutaneous core needle biopsy on diagnosing cardiac tumor and to discuss the treatment strategy for cardiac intermural and pericardial tumors. Methods: The clinical data were retrospectively collected for patients with intermural and pericardial cardiac tumors. The patients were divided into groups of surgical resection, surgical resection after obtaining pathological tissue by PUS-CNB, and/or radiotherapy according to the treatment modality. Ultrasound-guided aspiration biopsy was divided into cardiac tumor biopsy and extracardiac lesion biopsy according to patient conditions. The surgical time was recorded, and the safety and clinical application value of PUS-CNB for the diagnosis of cardiac tumors were evaluated in terms of complications and satisfaction with pathological sampling. Results: A total of 18 patient cases were collected, and PUS-CNB of cardiac tumors was performed in 8 cases, with sampling times averaging 15.6 ± 3.0 min. Four cases of cardiac tumors combined with extracardiac tumors were biopsied, with puncture times averaging 13.0 ± 2.9 min. All 12 biopsied patients had no postoperative complications. Except for 1 failed biopsy, the biopsies were successful and the pathological results were consistent with the clinical diagnosis with a satisfaction rate of 91.7%. Except for two cases of surgical resection, the rest were considered for conservative treatment. Surgical resection and/or biopsy were performed in six cases, and two cases were aggravated after surgery. The final pathology of all 17 cardiac tumors was malignant. Conclusion: PUS-CNB is safe and effective, providing a simple and undemanding method for accurate diagnosis of cardiac intermural and pericardial tumors while avoiding unnecessary open-heart surgery.

Evidence and assessment of parenchymal patterns of ultrasonography for breast cancer detection among Chinese women: a cross-sectional study.

BACKGROUND: Screening of breast cancer in asymptomatic women is important to evaluate for early diagnosis. In China ultrasound is a more frequently used method than mammography for the detection of breast cancer. The objectives of the study were to provide evidence and assessment of parenchymal patterns of ultrasonography for breast cancer detection among Chinese women. METHODS: Breast ultrasound examinations including the parenchymatous pattern of cytopathological confirmed breast cancer (n = 541) and age-matched cytopathological not confirmed breast cancer (n = 849) women were retrospectively reviewed by seven sonographer physicians. According to compositions of ducts, the thickness of the breast, diameter of ducts, fat lobules, and fibro glandular tissues, the breast parenchymatous pattern was categorized into heterogeneous (high percentage of fatty tissues), ductal (the inner diameters of ducts > 50% of the thick mass of the breast), mixed (the inner diameters of ducts was 50% of the thick mass of the breast), and fibrous categories (a dense classification of the breast). RESULTS: Heterogeneous (p < 0.0001, OR = 3.972) and fibrous categories (p < 0.0001, OR = 2.702) were higher among women who have cytopathological confirmed breast cancer than those who have not cytopathological confirmed breast cancer. The heterogeneous category was high-risk ultrasonographic examination category followed by the fibrous category. Agreements between sonographer physicians for categories of ultrasonic examinations were fair to good (Cohen's k = 0.591). CONCLUSIONS: Breast cancer risk in Chinese asymptomatic women differ according to the ultrasonographic breast parenchymal pattern. LEVEL OF EVIDENCE: III. Technical efficacy stage: 2.

The Basic Research of the Combinatorial Therapy of ABT-199 and Homoharringtonine on Acute Myeloid Leukemia.

BACKGROUND: Existing research shows that ABT-199, as a first-line drug, have been widely used in hematological malignancies, especially in leukemia, but the clinical efficacy of single drug therapy was limited part of the reason was that BCL-2 inhibitors failure to target other anti-apoptotic BCL-2 family proteins, such as MCL-1. In this case, combination therapy may be a promising way to overcome this obstacle. Here, we investigate the preclinical efficacy of a new strategy combining ABT-199 with homoharringtonine (HHT), a selective inhibitor of MCL-1 may be a promising approach for AML treatment as these two molecules are important in apoptosis. METHODS: A Cell Counting Kit-8 (CCK8) assay and flow cytometry were used to determine the half-maximal inhibitory concentration (IC50) value and cell apoptosis rate, respectively. The flow cytometry results showed that combined treatment with HHT and ABT-199 caused apoptosis in AML patient samples (n=5) but had no effect on normal healthy donor samples (n=11). Furthermore, we used a Western blot assay to explore the mechanism underlying the efficacy of HHT combined with ABT-199. Finally, antileukemic activity was further evaluated in vivo xenograft model. RESULTS: Our results indicated that ABT-199 combined with HHT significantly inhibited cell growth and promoted apoptosis in both AML cell lines and primary AML tumors in a dose- and time-dependent manner. Moreover, HHT combined with ABT-199 suppressed AML cell growth and progression in vivo xenograft model. CONCLUSIONS: Our research found that HHT combined with ABT-199 exerted its anti-leukemia effect by inducing apoptosis through the treatment of AML in vitro and in vivo.