Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Crown adjustment and chairside efficiency of single-unit restorations fabricated from immediate and staged impressions using a digital workflow for posterior implants.

PURPOSE: This is a clinical study to compare immediate and staged impression methods in a complete digital workflow for single-unit implants in the posterior area. MATERIALS AND METHODS: Sixty patients requiring single-unit implant crowns were enrolled. Forty patients were assigned to the test group, immediate digital impression after implant surgery with crown delivery 4 months later. The remaining 20 patients were assigned to the control group, staged digital impressions 4 months after implant surgery, and crown delivery 1 month later. Both workflows involved free-model CAD-CAM crown fabrications. The crowns were scanned before and after clinical adjustment using an intraoral scanner (TRIOS Color; 3Shape). Two 3D digital models were trimmed and superimposed to evaluate the dimensional changes using Geomagic Control software. Chairside times for the entire workflow were recorded. Kruskal-Wallis was performed to compare crown adjustments between two groups, while One-way ANOVA was used to compare chairside time durations between the test and control groups. RESULTS: All crowns were delivered without refabrication. The average maximum occlusion adjustment of crowns was -353.2 ± 207.1 µm in the test group and -212.7 ± 150.5 µm in the control group (p = 0.02). The average area of occlusal adjustment, measured as an area of deviation larger than 100 µm, was 14.8 ± 15.3 and 8.4 ± 8.1 mm2 in the test and control groups, respectively (p = 0.056). There were no significant differences in the mesial and distal contact adjustment amounts, or the maximum deviations of the proximal area, between the two groups. The mean chair-side time was 50.25 ± 13.48 and 51.20 ± 5.34 min in the test and control groups, respectively (p = 0.763). CONCLUSIONS: The immediate impression method in the digital workflow for single-unit implants required more occlusal adjustments of crowns but showed similar chairside times compared to the staged impression method.

A cell therapy approach based on iPSC-derived midbrain organoids for the restoration of motor function in a Parkinson's disease mouse model.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra and loss of DA transmission in the striatum, thus making cell transplantation an effective treatment strategy. Here, we develop a cellular therapy based on induced pluripotent stem cell (iPSC)-derived midbrain organoids. By transplanting midbrain organoid cells into the striatum region of a 6-OHDA-lesioned PD mouse model, we found that the transplanted cells survived and highly efficiently differentiated into DA neurons. Further, using a dopamine sensor, we observed that the differentiated human DA neurons could efficiently release dopamine and were integrated into the neural network of the PD mice. Moreover, starting from four weeks after transplantation, the motor function of the transplanted mice could be significantly improved. Therefore, cell therapy based on iPSC-derived midbrain organoids can be a potential strategy for the clinical treatment of PD.

MGIML: Cancer Grading with Incomplete Radiology-Pathology Data via Memory Learning and Gradient Homogenization.

Taking advantage of multi-modal radiology-pathology data with complementary clinical information for cancer grading is helpful for doctors to improve diagnosis efficiency and accuracy. However, radiology and pathology data have distinct acquisition difficulties and costs, which leads to incomplete-modality data being common in applications. In this work, we propose a Memory-and Gradient-guided Incomplete Modal-modal Learning (MGIML) framework for cancer grading with incomplete radiology-pathology data. Firstly, to remedy missing-modality information, we propose a Memory-driven Hetero-modality Complement (MH-Complete) scheme, which constructs modal-specific memory banks constrained by a coarse-grained memory boosting (CMB) loss to record generic radiology and pathology feature patterns, and develops a cross-modal memory reading strategy enhanced by a fine-grained memory consistency (FMC) loss to take missing-modality information from well-stored memories. Secondly, as gradient conflicts exist between missing-modality situations, we propose a Rotation-driven Gradient Homogenization (RG-Homogenize) scheme, which estimates instance-specific rotation matrices to smoothly change the feature-level gradient directions, and computes confidence-guided homogenization weights to dynamically balance gradient magnitudes. By simultaneously mitigating gradient direction and magnitude conflicts, this scheme well avoids the negative transfer and optimization imbalance problems. Extensive experiments on CPTAC-UCEC and CPTAC-PDA datasets show that the proposed MGIML framework performs favorably against state-of-the-art multi-modal methods on missing-modality situations.

Peri-zygomatic complications on zygomatic implants with or without penetrating the external surface of zygoma: A 2-year retrospective study.

OBJECTIVES: The main purpose of this retrospective study was to assess the difference in the incidence of peri-zygomatic complications (PZCs) when zygomatic implants (ZIs) penetrate or do not penetrate the external surface of zygoma. MATERIALS AND METHODS: This study included 32 patients with edentulous maxillae or potentially edentulous maxillae undergo zygomatic implantation. The patients were divided into the penetration group (P-group) and the non-penetration group (N-group) according to whether the apex of implants penetrated the external surface of zygoma in postoperative CBCT. The extension length, the penetration section of the implants, and the skin thickness at the corresponding position were simultaneously measured. Clinical follow-up was conducted regularly until 2 years after surgery. The occurrence of PZCs (including peri-zygomatic infection, skin numbness, non-infectious pain, and foreign body sensation) was recorded. A mixed effect logistic model was used to compare the difference of complication rate between the P-group and the N-group, and odds ratio (OR) was calculated. Then identify the impact of the extension length, penetration section and skin thickness in P-group with the same model. RESULTS: A total of 71 ZIs were implanted in 32 patients, including 37 implants in the P-group and 34 implants in the N-group. During the 2-year follow-up, a total of 13 implants occurred PZCs, with an overall complication rate of 18.3%. Thereinto, the incidence rate was 29.7% in the P-group, and 5.9% in the N-group (OR = 6.77). In P-group, there was a significant difference in complication rate of different extension lengths, while the penetration section and skin thickness had no statistical significance on the complication rate. CONCLUSION: Under the limitation of this study, to minimize the risk of PZCs, ZI should be placed in a manner that avoids the apex penetrating the external surface of the zygoma.

Cuproptosis-Associated lncRNA Gene Signature Establishes New Prognostic Profile and Predicts Immunotherapy Response in Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

Comparison of Cerebrospinal Fluid Cellular Analysis by Optical Microscopy and Sysmex XN 9000.

BACKGROUND: This study was designed to compare the body fluid module of Sysmex XN9000 (XN-BF) with optical microscopy (OM) for cerebrospinal fluid (CSF) analysis after two-step cell slide centrifuge (TSCSC), defining the best procedure for CSF optical microscopy analysis. METHODS: Items of RBC, WBC enumeration and differentiation were observed. The cell count and morphologic evaluation of the cellular composition by OM was carried out both with and without two-step cell slide centrifuge (TSCSC) and were compared the data with XN-BF. RESULTS: There were 69.98 ± 4.94 RBC and 36.98 ± 3.39 WBC in one OSCSC microscopic field whereas there were 96.35 ± 5.41 RBC and 66.15 ± 4.85 WBC in one TSCSC microscopic field in the same sample (*200). There was a statistical difference between those two methods (p = 0.000). Excellent correlation was found between total cell count with both OM and XN-BF. The R2 value for RBC and WBC counts were 0.99 and 0.96, respectively. For WBC differential, the R2 values were 0.98 for PMN and 0.70 for MN. Correlation of MN was poorer than PMN. As far as the tumor cell, phagocyte, and plasma cell with high fluorescence were concerned, OM were not consistent with XN-BF. CONCLUSIONS: The TSCSC procedure contributes to the separation of cells and other ingredients. XN-BF displays excellent performance at RBC and WBC cell count except for mononuclear cells, tumor cells, phagocytes, and leukemia cells. which makes it just a practical alternative to total cell (WBC, RBC) count for CSF samples. Detailed morphologic workup of CSF samples is mandated in all cases with meningoencephalitis, elevated cell count, sub-arachnoid hemorrhage and meningeal carcinomatosis, the TSCSC procedure is recommended.

Single-cell and spatial architecture of primary liver cancer.

Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.

[Inhibition of Ferulic Acid on U937 Cell Growth and Its Related Mechanism].

OBJECTIVE: To investigate the effects of ferulic acid (FA) on proliferation, apoptosis and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway of human acute myeloid leukemia (AML) U937 cells. METHODS: Different concentrations of FA (0、10、25、50、100、200 µmol/L) was used to treat human AML cell lines Kasumi-1, HL-60, and U937 cells respectively for 24 h. The cell survival rate was detected by cell counting kit-8 method, and the 50% inhibitory concentration (IC50) of each cell line was calculated. The U937 cells were divided into control group, FA group (50 µmol/L FA), FA+pcDNA group (50 µmol/L FA+transfected with empty plasmid), FA+pcDNA-TLR4 group (50 µmol/L FA+transfected with TLR4 overexpression plasmid). Flow cytometry was used to detect U937 cell cycle and cell apoptosis; plate clone formation test was used to detect U937 cell clone formation ability; fluorescence quantitative PCR was used to detect the TLR4, NF-κB p65 mRNA levels in U937 cells; Western blot was used to detect the expression levels of CyclinD1, CyclinE, Bcl-2 related X protein (Bax), B cell lymphoma-2 (Bcl-2), Caspase-3, TLR4, and NF-κB p65 protein in U937 cells. RESULTS: With the increase of FA concentration, the survival rates of Kasumi-1, HL-60 and U937 cells gradually decreased(r=-0.919, r=-0.909, r=-0.900), the IC50 of U937 cells was 50.25±2.23 µmol/L. Compared with the control group, after drug treatment of U937 cells, the ratio of G0/G1 phase cells, apoptosis rate, expression levels of Bax and Caspase-3 proteins in FA group were significantly increased (P<0.05), the number of cell clones, the ratios of S phase and G2/M phase cells, expression levels of CyclinD1, CyclinE and Bcl-2 proteins, and TLR4, NF-κB p65 mRNA and protein were significantly decreased (P<0.05); compared with FA group and FA+pcDNA group, the ratio of G0/G1 phase cells, apoptosis rate, expression levels of Bax and Caspase-3 proteins in FA+pcDNA-TLR4 group were significantly decreased (P<0.05), the number of cell clones, the ratios of S phase and G2/M phase cells, expression levels of expression levels of CyclinD1, CyclinE and Bcl-2 proteins, and TLR4, NF-κB p65 mRNA and proteins were significantly increased (P<0.05). CONCLUSION: FA inhibits U937 cell proliferation and promotes cell apoptosis by inhibiting the TLR4/NF-κB signaling pathway.

[Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5].

OBJECTIVE: To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme. METHODS: The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests. RESULTS: Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001). CONCLUSION: For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.

Lateral sinus floor elevation in patients with sinus floor defects: A retrospective study with a 1- to 9-year follow-up.

OBJECTIVES: We aimed to retrospectively evaluate the long-term clinical outcomes of lateral sinus floor elevation (LSFE) in patients with sinus floor defects. MATERIALS AND METHODS: Between 2008 and 2020, patients with sinus floor defects were recruited after confirmation on preoperative cone-beam computed tomography (CBCT). The split-thickness flap technique with a palatal crestal incision was used to manage tissue adhesion in the bone defects area. A resorbable collagen membrane was used to close the sinus floor defects from the crestal side before bone substitute placement. Of 58 implants, 47 (81.0%) were placed after an 8-month healing period, whereas 11 were placed simultaneously. Patients were followed up by radiography and clinical examination for 1-9 years. Finally, the cumulative survival rate (CSR) of implants, surgical complications, and marginal bone loss (MBL) were recorded and analyzed. RESULTS: In total, LSFE was performed in 36 sinuses (35 patients) with sinus floor defects, of which surgery was completed in 35 sinuses (97.2%) in the first attempt. Schneiderian membrane perforations (SMP) occurred in 10/36 (27.8%) sinuses; nine were repaired carefully, whereas one surgery was suspended due to complicated SMP, and successful re-entry LSFE was performed 4 months later. After a follow-up period of 1-9 years, the CSR was 96.5% at the 1-year, 3-year, 5-year, and 7-year follow-ups and 64.3% at the 8-year follow-up. CONCLUSION: Within the limitations of this study, sinus floor defects seem not to compromise LSFE therapy after appropriate management and long-term clinical outcomes are predictable.

Diagnostic value of aberrant decreased 5-Methylcytosine RNA modification in leukocytes for non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) was a disease with poor outcomes, partly because there were no high-efficiency non-invasive diagnostic biomarkers. The RNA modification status of 5-Methylcytosine (m5C) has been shown to be a biomarker for various diseases, but its potentiality to be a diagnostic biomarker for NSCLC remained inconclusive. Methods: In this research, we collected peripheral leukocyte samples from 141 patients with NSCLC and 90 normal people as controls to evaluate the extent of m5C RNA modification. Results: We found that the m5C modification levels in leukocytes of NSCLC patients were decreased dramatically, which were compared to the normal controls, and levels of m5C modification decreased progressively with tumor stage. Importantly, m5C modification exhibited superior diagnostic value compared to carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), and carbohydrate antigen 125 (CA125), which demonstrated area under the curves (AUCs) of 0.912, 0.773, 0.669, 0.754, and 0.732, respectively. The combination of m5C modification with these serum tumor biomarkers further improved the AUC to 0.960. A nomogram model incorporating m5C modification also provided an effectively diagnostic tool for NSCLC. Conclusion: Collectively, our findings suggested that m5C modification in leukocytes held promise as a prospective biomarker for NSCLC diagnosis.

Identification and validation of a novel anoikis-related signature for predicting prognosis and immune landscape in ovarian serous cystadenocarcinoma.

Background: Ovarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies. Methods: The mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups. Results: We identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score (rs = -0.21, P < 0.05). Ultimately, quantitative reverse transcription polymerase chain reaction (RT-PCR) was utilized to validate the expression of the seven pivotal ARGs. Conclusion: In this study, based on seven ARGs, a risk model and nomogram established can be used for risk stratification and prediction of survival outcomes in patients with OSC, providing a reliable reference for individualized therapy of OSC patients.

The use of magnet-controlled capsule endoscopy as the initial diagnostic tool in patients with acute upper gastrointestinal bleeding.

BACKGROUND: The latest magnet-controlled capsule endoscopy (MCCE) system can examine the water-distended stomach, duodenum, and the small bowel. We assessed the use of MCCE as the first diagnostic tool in patients with acute upper gastrointestinal bleeding (AUGIB). METHODS: This was a prospective cohort study that enrolled patients admitted with AUGIB from two teaching hospitals. Patients underwent MCCE as the initial diagnostic modality. Our primary endpoint was the diagnostic yield of MCCE. The subsequent care of these patients was guided by MCCE findings. RESULTS: Of 100 enrolled patients, 99 (mean age 54 years, 70.7% men) with a median Glasgow-Blatchford score of 6 (IQR 3-9) underwent MCCE. In three patients, MCCE found active bleeding (two duodenal ulcers and Dieulafoy's lesion). The overall diagnostic yield of MCCE was 95.8% (92 lesions in 96 patients); five in the esophagus (Mallory Weiss tears 2, varices 1, and esophagitis 2), 51 in the stomach (gastric erosions 26, gastric ulcers 14, cancer 3, GIST 3, gastric polyps 3, antral vascular ectasia 1,angiodysplasia 1), 32 in the duodenum (ulcers 28, erosions 3, polyp 1), and four in the small bowel (ulcers 2, an erosion with a nonbleeding vessel 1, Meckel's diverticulum 1). Fifty-two (52.5%) patients were discharged without endoscopy. Forty-five (45.5%) patients underwent inpatient esophagogastroduodenoscopy (EGD), which found an antral ulcer and six duodenal ulcers in addition. CONCLUSIONS: In stable patients with AUGIB, MCCE can be used as a diagnostic tool. EGD should follow in patients with an inadequate view of the duodenum.

Non-selective beta-blockers and the incidence of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.

Background: Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients. Aim: To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis. Methods: We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case‒control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed. Results: A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10), p = 0.000, and I2 = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62-1.44) or timolol (OR = 1.32 and 95%CI 0.44-3.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64-0.86) and carvedilol (OR = 0.62 and 95%CI 0.52-0.74), respectively. Conclusion: Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America. Systematic Review Registration: identifier https://CRD42023434175, https://www.crd.york.ac.uk/PROSPERO/.

ARU-GAN: U-shaped GAN based on Attention and Residual connection for super-resolution reconstruction.

Plane-wave ultrasound imaging technology offers high-speed imaging but lacks image quality. To improve the image spatial resolution, beam synthesis methods are used, which often compromise the temporal resolution. Herein, we propose ARU-GAN, a super-resolution reconstruction model based on residual connectivity and attention mechanisms, to address this issue. ARU-GAN comprises a Full-scale Skip-connection U-shaped Generator (FSUG) with an attention mechanism and a Residual Attention Patch Discriminator (RAPD). The former captures global and local features of the image by using full-scale skip-connections and attention mechanisms. The latter focuses on changes in the image at different scales to enhance its discriminative ability at the patch level. ARU-GAN was trained using a combined loss function on the Plane-Wave Imaging Challenge in Medical Ultrasound (PICMUS) 2016 dataset, which includes three types of targets: point targets, cyst targets, and in-vivo targets. Compared to Coherent Plane-Wave Compounding (CPWC), ARU-GAN achieved a reduction in Full Width at Half Maximum (FWHM) by 5.78%-20.30% on point targets, improved Contrast (CR) by 7.59-11.29 percentage points, and Contrast to Noise Ratio (CNR) by 30.58%-45.22% on cyst targets. On in-vivo target, ARU-GAN improved the Peak Signal-to-Noise Ratio (PSNR) by 11.94%, the Complex-Wavelet Structural Similarity Index Measurement (CW-SSIM) by 17.11%, and the Normalized Cross Correlation (NCC) by at least 2.17% compared to existing deep learning methods. In conclusion, ARU-GAN is a promising model for the super-resolution reconstruction of plane-wave medical ultrasound images. It provides a novel solution for improving image quality, which is essential for clinical practice.

Polyporus umbellatus polysaccharide iron-based nanocomposite for synergistic M1 polarization of TAMs and combinational anti-breast cancer therapy.

M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials.

DEF6(differentially exprehomolog) exacerbates pathological cardiac hypertrophy via RAC1.

Pathological cardiac hypertrophy involves multiple regulators and several signal transduction pathways. Currently, the mechanisms of it are not well understood. Differentially expressed in FDCP 6 homolog (DEF6) was reported to participate in immunity, bone remodeling, and cancers. The effects of DEF6 on pathological cardiac hypertrophy, however, have not yet been fully characterized. We initially determined the expression profile of DEF6 and found that DEF6 was upregulated in hypertrophic hearts and cardiomyocytes. Our in vivo results revealed that DEF6 deficiency in mice alleviated transverse aortic constriction (TAC)-induced cardiac hypertrophy, fibrosis, dilation and dysfunction of left ventricle. Conversely, cardiomyocyte-specific DEF6-overexpression aggravated the hypertrophic phenotype in mice under chronic pressure overload. Similar to the animal experiments, the in vitro data showed that adenovirus-mediated knockdown of DEF6 remarkably inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas DEF6 overexpression exerted the opposite effects. Mechanistically, exploration of the signal pathways showed that the mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase 1/2 (ERK1/2) cascade might be involved in the prohypertrophic effect of DEF6. Coimmunoprecipitation and GST (glutathione S-transferase) pulldown analyses demonstrated that DEF6 can directly interact with small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1), and the Rac1 activity assay revealed that the activity of Rac1 is altered with DEF6 expression in TAC-cardiac hypertrophy and PE-triggered cardiomyocyte hypertrophy. In the end, western blot and rescue experiments using Rac1 inhibitor NSC23766 and the constitutively active mutant Rac1(G12V) verified the requirement of Rac1 and MEK1/2-ERK1/2 activation for DEF6-mediated pathological cardiac hypertrophy. Our study substantiates that DEF6 acts as a deleterious regulator of cardiac hypertrophy by activating the Rac1 and MEK1/2-ERK1/2 signaling pathways, and suggests that DEF6 may be a potential treatment target for heart failure.