Ultrasomics differentiation of malignant and benign focal liver lesions based on contrast-enhanced ultrasound.

OBJECTIVES: To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). METHODS: 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. RESULTS: In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P < 0.05). In the validation cohort, the AUC of combined nomogram and expert was significantly higher than that of the resident (91.4% vs. 89.5% vs. 79.3%, P < 0.05). The combined nomogram had a comparable sensitivity with the expert and resident (95.2% vs. 98.4% vs. 97.6%), while the expert had a higher specificity than the nomogram and the resident (80.6% vs. 72.2% vs. 61.1%, P = 0.205). CONCLUSIONS: A CEUS ultrasomics based nomogram had an expert level performance in FLL characterization.

Relationship between right-to-left shunt and white matter lesions in patients with migraine: a single-center study.

Background: Migraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs. Methods: In this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs). Results: Among the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p < 0. 001) and a shorter disease duration (6.76 vs. 8.34 years, p = 0.024). The overall proportion of RLS patients was 41.9%, with a greater proportion of RLS patients in the MA group than in the MO group (55.8% vs. 41. 1%, p = 0.037). The percentage of RLS-positive patients with no/small shunt was greater in the MO group than in the MA group (81.5% vs. 65.4%, p = 0.004), whereas the percentage of RLS-positive patients with moderate/large shunt was greater in the MA group (34.6% vs. 18.5%, p = 0.024). The proportion of RLS patients was lower in the WML-positive group (n = 173) than in the WML-negative group (n = 332), but the difference was not significant (40.5% vs. 45.8%, p = 0.253). Conclusion: This study revealed that 41.9% of migraine patients had RLS, and the proportion of RLS patients was 41. 1% in the MO group and 55.8% in the MA group. The rate of RLS positivity in migraine patients may not be related to the incidence of WMLs.

Kinesin-7 CENP-E mediates centrosome organization and spindle assembly to regulate chromosome alignment and genome stability.

Chromosome congression and alignment are essential for cell cycle progression and genomic stability. Kinesin-7 CENP-E, a plus-end-directed kinesin motor, is required for chromosome biorientation, congression and alignment in cell division. However, it remains unclear how chromosomes are aligned and segregated in the absence of CENP-E in mitosis. In this study, we utilize the CRISPR-Cas9 gene editing method and high-throughput screening to establish CENP-E knockout cell lines and reveal that CENP-E deletion results in defects in chromosome congression, alignment and segregation, which further promotes aneuploidy and genomic instability in mitosis. Both CENP-E inhibition and deletion lead to the dispersion of spindle poles, the formation of the multipolar spindle and spindle disorganization, which indicates that CENP-E is necessary for the organization and maintenance of spindle poles. In addition, CENP-E heterozygous deletion in spleen tissues also leads to the accumulation of dividing lymphocytes and cell cycle arrest in vivo. Furthermore, CENP-E deletion also disrupts the localization of key kinetochore proteins and triggers the activation of the spindle assembly checkpoint. In summary, our findings demonstrate that CENP-E promotes kinetochore-microtubule attachment and spindle pole organization to regulate chromosome alignment and spindle assembly checkpoint during cell division.

AQP4 is upregulated in schizophrenia and Its inhibition attenuates MK-801-induced schizophrenia-like behaviors in mice.

BACKGROUND: The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms. METHODS: Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 µM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of AQP4, proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors. RESULTS: Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of AQP4 was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of IL-1ß, IL-6, and TNF-α in MK-801-treated C6 cells and mouse model. CONCLUSIONS: AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.

Stereotactic Body Radiation Adoption Impacts Prostate Cancer Treatment Patterns.

OBJECTIVE: To investigate stereotactic body radiation (SBRT) adoption for prostate cancer. As evidence supporting SBRT mounts, its utilization and impact relative to other prostate cancer treatments is unknown. METHODS: We used SEER-Medicare to identify patients diagnosed with localized prostate cancer from 2008 to 2017. We then identified physician networks by identifying the primary treating physician of each patient based on primary treatment, then linking each physician to a practice. We examined trends in prostate cancer treatment between networks performing SBRT or not using chi-squared tests and logistic regression models. RESULTS: There were 35,972 patients who received treatment for prostate cancer at 234 physician networks. Of these patients, 30,635 were treated in a non-SBRT network (n = 190), while 5337 received treatment in a SBRT network (n = 44). Patients who received care in an SBRT network were more likely to live in metropolitan areas ≥1 million (70% vs 46%, P <.001), have a higher median income >$60,000 (62% vs 42%, P <.001), and live in the northeast (35% vs 12%) or west (40% vs 38%, P <.001) compared to non-SBRT networks. In SBRT networks, more patients received IMRT (31% vs 23%), and fewer patients received prostatectomy (16% vs 23%) or active surveillance (15% vs 19%) compared to non-SBRT networks. Black men were 45% less likely to receive SBRT (OR=0.55, CI: 0.36-0.85) compared to White men. CONCLUSION: SBRT utilization is increasing relative to other prostate cancer treatments. Prostate cancer treatment mix is different in networks that offer SBRT, and SBRT is less available to some patient groups, raising concern for novel treatment inequity.

Frontiers and hotspots evolution in anti-inflammatory studies for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that seriously affects the quality of the elderly's lives worldwide. The main pathological features of AD are amyloid plaques formed by ß-amyloid (Aß) and neuronal fibrillary tangls (NFTs) formed by hyperphosphorylated Tau protein. The formation process of these pathological features is closely related to inflammatory response, so anti-inflammatory treatment has become a potential treatment for AD. In recent years, more and more research has shown that the anti-inflammatory therapy can relieve the symptoms of AD and improve cognitive function, which provides a valuable research direction for the treatment of AD strategy. Therefore, a comprehensive understanding of the hotspots and development trends of AD anti-inflammatory research is important for promoting the further development of this field and improving the quality of life of patients. METHODS: This study used bibliometric methods, with AD and anti-inflammatory as key words, collected 7638 AD anti-inflammatory studies collected in Web of Science Core Collection (WoSCC) literature database since 2000, and conducted an in-depth analysis of the research hotspots and potential trends in this field. RESULTS: The depth and breadth of AD anti-inflammatory research are in the stage of rapid development, and the hot focus is on exploring the role of inflammation in the pathogenesis of AD, especially the interaction of microglia in the neuroinflammatory mechanism. Secondly, the treatment effect and potential risks of anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) on AD are also the focus of research. Therefore, researchers have carried out a series of animal experiments and prospective clinical studies on anti-inflammatory drugs for the treatment of AD, forming a comprehensive research system from basic research to clinical research. As for the future development trend, we believe that the further exploration of inflammation in the pathogenesis of AD will still be one of the key directions, and the application of big data and artificial intelligence technology is expected to provide strong support for the association between inflammation and AD progression. Moreover, the development of novel anti-inflammatory drugs for the inflammatory mechanism of AD will be another major trend for future research. At the same time, personalized treatment strategies and alternative supplements of medicine will also become one of the hotspots of future research. Through the comprehensive use of anti-inflammatory drugs, nutritional supplements, lifestyle intervention and other means, more comprehensive and effective treatment plans for AD patients are expected. CONCLUSION: This research analyzes the overall development trend of AD anti-inflammatory research field since 2000, and provides a comprehensive perspective for the progress of AD anti-inflammatory research. Overall, the field of AD anti-inflammatory research is facing a broad development prospect. In the future, with further research and technological advances, we have resason to expect more effective and safer treatment options for AD patients to help them improve their quality of life and delay disease progression.

Clinical and computed tomography angiography characteristics of infected vs. non-infected abdominal aortic aneurysm: a comparative study.

PURPOSE: The aim of this study was to investigate the clinical and multi-slice spiral computed tomography angiography (MSCTA) characteristics for the diagnosis of infected AAA. METHODS: This retrospective comparative study included patients who were diagnosed with AAA at our hospital between January 2014 and May 2023. RESULTS: A total of 40 patients were included, comprising 20 with infected AAA and 20 with non-infected AAA. Patients with infected AAA were more likely to be younger (62.9 ± 10.1 vs. 70.0 ± 4.4 years, P = 0.007) and to present with fever [7 (35%) vs. 1 (5%), P = 0.026], pain [15 (75%) vs. 2 (10%), P < 0.001], higher C-reactive protein levels (60.4 ± 57.0 vs. 4.1 ± 2.9 mg/l, P = 0.005), and higher erythrocyte sedimentation rates (47.7 ± 23.4 vs. 15.2 ± 8.3 mm/h, P < 0.001) compared to those with non-infected AAA. Moreover, those with infected AAA exhibited significantly more eccentric saccular morphology [17 (85%) vs. 1 (5%), P = 0.002], a smaller longitudinal-transverse ratio (1.12 ± 0.33 vs. 2.33 ± 0.54, P = 0.001), thicker peri-aneurysmal soft tissue (2.29 ± 1.48 vs. 0.73 ± 0.55 cm, P < 0.001), more lobulated margins [18 (90%) vs. 1 (5%), P = 0.001], lower aortic calcification scores (49 vs. 56, P < 0.001), more pneumatosis [6 (30%) vs. 0 (0%), P = 0.014], more ruptures [15 (75%) vs. 5 (20%), P = 0.002], more blurred peri-abdominal aortic fat spaces [16 (80%) vs. 2 (10%), P = 0.001], more adjacent bone destruction [5 (25%) vs. 0 (0%), P = 0.025], more involvement of the psoas major muscle [8 (40%) vs. 1 (5%), P = 0.005], more lymphadenectasis [8 (40%) vs. 1 (5%), P = 0.020], and less tortuous aortas [2 (10%) vs. 9 (45%), P = 0.034] compared with those with non-infected AAA. CONCLUSION: The clinical manifestations and MSCTA characteristics may differ between infected and non-infected AAA.

Mechanisms of enhancing MgO for stabilization/solidification of Pb-contaminated red clay through CO2 sequestration.

Pb-contaminated soil poses significant environmental and health risks as well as soil stability issues. Research on sandy soils highlights CO2-enhanced reactive MgO as a promising solution for improving the solidification of Pb-contaminated soils. However, carbonation effects can differ markedly between soil types owing to varying soil properties. In this study, we evaluated the effects of CO2-enhanced reactive MgO on the engineering and environmental characteristics of Pb-contaminated red clay and explored its mechanism of carbonation solidification. The results showed that CO2-enhanced reactive MgO increased the strength of Pb-contaminated red clay to over 3 MPa within 1 h, which was approximately 25 times the strength of untreated soil (0.2 MPa) and significantly higher than that of reactive MgO-treated, uncarbonated soil (0.8 MPa). The pH of the carbonated soil (9-10) facilitated Pb2+ immobilization, and the increase over the initial parameter elevated the electrical conductivity value. Moreover, CO2-enhanced reactive MgO reduced the Pb2+ leaching concentration to below 0.1 mg/L, even at high Pb concentrations (10,000 mg/kg). Pb2+ transformed into lead carbonates during the carbonation process, with the hydrated magnesium carbonates forming a dense internal structure. This solidification mechanism included chemical precipitation, physical adsorption, and encapsulation. Notably, the carbonation time should be controlled within 1 h to prevent soil expansion. Together, these findings support the potential of CO2-enhanced reactive MgO for efficient and low-carbon application in the solidification of Pb-contaminated red clay.

Cathepsin S (CTSS) in IgA nephropathy: an exploratory study on its role as a potential diagnostic biomarker and therapeutic target.

Introduction: IgA nephropathy (IgAN), a prevalent form of glomerulonephritis globally, exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various physiological and pathological processes, including renal conditions. Prior observational studies have suggested a potential link between cathepsins and IgAN, yet the precise causal relationship remains unclear. Methods: We conducted a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data to explore the causal association between cathepsins and IgAN systematically. Additionally, immunohistochemical (IHC) staining and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. We investigated the underlying mechanisms via gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Molecular docking and virtual screening were also performed to identify potential drug candidates through drug repositioning. Results: Univariate MR analyses demonstrated a significant link between increased cathepsin S (CTSS) levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009-1.073, P=0.012) as estimated using the inverse variance weighting (IVW) method. In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels continued to show a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037, 95% CI=1.006-1.069). However, reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins. IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. Investigations into immune cell infiltration, GSEA, and GSVA highlighted the role of CTSS expression in the immune dysregulation observed in IgAN. Molecular docking and virtual screening pinpointed Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS. Conclusion: Elevated CTSS levels are associated with an increased risk of IgAN, and this enzyme is notably overexpressed in IgAN patients' serum and renal tissues. CTSS could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating IgAN.

Willingness to use smart fetal heart rate monitoring devices among pregnant women: an extension of the technology acceptance model.

The purpose of this study was to assess the significant factors that impact pregnant women's willingness to use smart fetal heart-rate monitoring devices. We propose a research model that integrates technological factors (perceived compatibility and perceived credibility) and personal factors (health anxiety, personal physiological conditions, health consciousness, and health beliefs). The subjects of this study were Chinese women who were pregnant or had previously given birth. Data were collected and analyzed from 397 paper-and-pencil and electronic questionnaires. Our structural equation model indicated that perceived usefulness (ß = 0.490, t = 7.591, p < 0.001), perceived ease of use (ß = 0.352, t = 5.631, p < 0.001), health anxiety (ß = 0.095, t = 2.664, p = 0.008), personal physiological conditions (ß = 0.075, t = 2.142, p = 0.032), and health consciousness (ß = 0.078, t = 2.110, p = 0.035) were the determinants of the intention to use smart fetal heart-rate monitoring devices, with perceived usefulness having the highest degree of influence. Furthermore, we discovered that the levels of perceived compatibility and perceived credibility did not have direct correlations with the intention to use these devices, but they did significantly influence the model. Perceived compatibility (ß = 0.345, t = 6.601, p < 0.001) and perceived credibility (ß = 0.519, t = 9.958, p < 0.001) significantly influences perceived ease of use. Perceived credibility (ß = 0.421, t = 7.802, p < 0.001) significantly influences perceived usefulness. Based on these results, suggestions for future research are put forward.

Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.

BACKGROUND AND HYPOTHESIS: Zinc finger protein 804A (ZNF804A) was the first genome-wide associated susceptibility gene for schizophrenia (SCZ) and played an essential role in the pathophysiology of SCZ by influencing neurodevelopment regulation, neurite outgrowth, synaptic plasticity, and RNA translational control; however, the exact molecular mechanism remains unclear. STUDY DESIGN: A nervous-system-specific Zfp804a (ZNF804A murine gene) conditional knockout (cKO) mouse model was generated using clustered regularly interspaced short palindromic repeat/Cas9 technology and the Cre/loxP method. RESULTS: Multiple and complex SCZ-like behaviors, such as anxiety, depression, and impaired cognition, were observed in Zfp804a cKO mice. Molecular biological methods and targeted metabolomics assay validated that Zfp804a cKO mice displayed altered SATB2 (a cortical superficial neuron marker) expression in the cortex; aberrant NeuN, cleaved caspase 3, and DLG4 (markers of mature neurons, apoptosis, and postsynapse, respectively) expressions in the hippocampus and a loss of glutamate (Glu)/γ-aminobutyric acid (GABA) homeostasis with abnormal GAD67 (Gad1) expression in the hippocampus. Clozapine partly ameliorated some SCZ-like behaviors, reversed the disequilibrium of the Glu/GABA ratio, and recovered the expression of GAD67 in cKO mice. CONCLUSIONS: Zfp804a cKO mice reproducing SCZ-like pathological and behavioral phenotypes were successfully developed. A novel mechanism was determined in which Zfp804a caused Glu/GABA imbalance and reduced GAD67 expression, which was partly recovered by clozapine treatment. These findings underscore the role of altered gene expression in understanding the pathogenesis of SCZ and provide a reliable SCZ model for future therapeutic interventions and biomarker discovery.

A Patient With Proteinuria, Myalgias, and Decreased Pigmentation of Facial Skin.

A patient had bilateral leg edema, insomnia, myalgias, paresthesias in the fingertips, lighter pigmentation of the facial skin compared with other areas of the body, proteinuria, and an elevated creatinine level. What is the diagnosis and what would you do next?

The role of Atg5 gene in tumorigenesis under autophagy deficiency conditions.

Autophagy is a self-recycling machinery to maintain cellular homeostasis by degrading harmful materials in the cell. Autophagy-related gene 5 (Atg5) is required for autophagosome maturation. However, the role of Atg5 in tumorigenesis under autophagy deficient conditions remains unclear. This study focused on the autophagy-independent role of Atg5 and the underlying mechanism in tumorigenesis. We demonstrated that knockout of autophagy-related genes including Atg5, Atg7, Atg9, and p62 in mouse embryonic fibroblast (MEF) cells consistently decreased cell proliferation and motility, implying that autophagy is required to maintain diverse cellular functions. An Atg7 knockout MEF (Atg7-/- MEF) cell line representing deprivation of autophagy function was used to clarify the role of Atg5 transgene in tumorigenesis. We found that Atg5-overexpressed Atg7-/-MEF (clone A) showed increased cell proliferation, colony formation, and migration under autophagy deficient conditions. Accordingly, rescuing the autophagy deficiency of clone A by overexpression of Atg7 gene shifts the role of Atg5 from pro-tumor to anti-tumor status, indicating the dual role of Atg5 in tumorigenesis. Notably, the xenograft mouse model showed that clone A of Atg5-overexpressed Atg7-/- MEF cells induced temporal tumor formation, but could not prolong further tumor growth. Finally, biomechanical analysis disclosed increased Wnt5a secretion and p-JNK expression along with decreased ß-catenin expression. In summary, Atg5 functions as a tumor suppressor to protect the cell under normal conditions. In contrast, Atg5 shifts to a pro-tumor status under autophagy deprivation conditions.

Association between exposure to organophosphorus pesticide and suicidal ideation among U.S. adults: A population-based study.

OBJECTIVE: This study aims to investigate the potential link between exposure to organophosphorus pesticides (OPPs) and suicidal ideation (SI) among adults. METHODS: This study encompassed four cycles of the National Health and Nutrition Examination Survey (NHANES), involving 5244 participants aged 20 and above. SI was assessed using the Patient Health Questionnaire-9. The levels of exposure to OPPs were estimated by analyzing concentrations of OPP metabolites in urine samples. Multivariate logistic regression models were used to explore the association between exposure to each OPP and SI. Stratified analyses and interaction tests were conducted across various groups, including pairwise combinations of gender and age, as well as body mass index, smoking status, hypertension, and diabetes. Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) models were applied to assess the cumulative impact of exposure to the four OPPs on SI, along with their respective contributions. Additionally, the potential interactions among these four OPPs were evaluated. RESULTS: Multivariate logistic regression revealed that only dimethylthiophosphate (DMTP) among OPPs demonstrated a statistically significant positive association with SI [OR: 1.18; 95 % CI: 1.02-1.37]. Stratified analyses indicated that the influence of OPPs on SI was particularly pronounced in young and older men. The WQS regression analysis revealed a statistically significant association between the mixed metabolites of OPPs and SI [OR = 1.10, 95 % CI: 1.04-1.16], with DMTP (weighted 0.63) contributing the most. Furthermore, the BKMR model supported a positive trend in the overall impact of these OPP metabolites on SI, displaying notable individual exposure-response relationships for DMTP (PIP: 0.77). CONCLUSIONS: Our study suggests an association between exposure to DMTP and an increased risk of SI. Specifically, young adult males and older males appear particularly susceptible to the effects of OPP exposure.

Abnormal methylation of HOXA11 promoter promotes tumor progression in testicular germ cell tumor.

OBJECTIVE: To investigate the methylation of HOXA11 gene promoter in testicular germ cell tumor (GCT). METHOD: The clinicopathological data of 63 patients with primary testicular GCT who underwent surgery during Apr. 2019 to Mar. 2021, were retrospectively analyzed. Their GCT tissue and paraneoplastic testicular tissue were obtained, and genomic DNA was extracted from both. The methylation of HOXA11 gene promoter region was detected by methylation-specific PCR (MSP). The incidence of HOXA11 methylation in testicular GCT and adjacent tissues was compared, and the connection between methylation level in testicular GCT and clinicopathologic features of patients was statistically analyzed. Testicular GCT cells were treated with methylated transferase inhibitor 5-Aza-dC in vitro, and HOXA11 mRNA expression was detected by real-time PCR. RESULTS: The positive rate of HOXA11 promoter methylation in testicular GCT tissues was notably higher than that of paired adjacent tissues (P<0.05). The abnormal methylation of HOXA11 gene promoter was correlated with lymph node metastasis and TNM stage in patients (P<0.05). HOXA11 mRNA expression in testicular GCT cells treated with 5-Aza-dC was increased (P<0.05). CONCLUSION: Abnormal methylation of HOXA11 gene promoter in testicular germ cell tumor tissue inhibits transcription and expression of HOXA11 gene. The abnormal methylation of HOXA11 promoter region is tightly associated with lymph node metastasis and TNM staging in testicular germ cell tumors.

Efficacy of real-time artificial intelligence-aid endoscopic ultrasonography diagnostic system in discriminating gastrointestinal stromal tumors and leiomyomas: a multicenter diagnostic study.

Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.

Dual-mRNA Delivery Using Tumor Cell Lysate-Based Multifunctional Nanoparticles as an Efficient Colon Cancer Immunogene Therapy.

Background: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.

The Impact of Sarcopenia on the Clinical Outcomes of Percutaneous Kyphoplasty in Patients With Osteoporotic Vertebral Compression Fracture: A Retrospective Cohort Study.

Objective: This study aimed to explore the impact of sarcopenia on clinical outcomes after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF). Methods: We retrospectively analyzed the medical records of patients with single-segment OVCF who underwent percutaneous kyphoplasty (PKP) between September 2021 and August 2022. Patients were categorized into a sarcopenia group (43 patients) and a non-sarcopenia group (125 patients) based on their Advanced Skeletal Muscle Index (ASMI). Clinical and radiological data were collected and analyzed. Results: There were no significant differences between the sarcopenia and non-sarcopenia groups in age, sex, bone mineral density (BMD), body mass index (BMI), fractured segment, fracture type, surgical approach, bone cement volume, bone cement distribution, comorbidities, preoperative and immediate postoperative VAS and ODI scores (P > .05). However, the time to ambulation, hospital stays, VAS and ODI scores at follow-up, excellent/good rate, and the incidence of residual pain and re-fractures in the non-sarcopenia group were significantly better than those in the sarcopenia group (P < .05). Meanwhile, radiological outcomes, including regional kyphosis and vertebral height loss rate, were significantly better in the non-sarcopenia group than in the sarcopenia group at 6 and 12 month follow-ups (P < .05). Conclusion: Clinical outcomes after PKP in patients with OVCF could be negatively affected by sarcopenia. Therefore, prevention and treatment of sarcopenia should be actively considered in the management of patients with OVCF.