Hsa_circ_0001615 downregulation inhibits esophageal cancer development through miR-142-5p/ß-catenin.

Background: Recent studies have found that circular RNAs (circRNAs) play important roles in tumorigenesis. This study aimed to determine the function and potential mechanisms of hsa_circ_0001615 in esophageal cancer. Methods: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the expression of hsa_circ_0001615 and miR-142-5p. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt, flow cytometry, clone formation, and transwell assays were used to assess the function of hsa_circ_0001615. Furthermore, qRT-PCR and Western blot analysis were used to verify cyclin D1, Bcl-2 associated X, B-cell lymphoma/leukemia gene-2, and ß-catenin levels. Circular RNA Interactome was used to estimate the binding site between hsa_circ_0001615 and miR-142-5p. Additionally, dual-luciferase reporter assays were used to determine whether miR-142-5p was a direct target of hsa_circ_0001615. Pearson correlation analysis was used to explore the relationship between miR-142-5p and hsa_circ_0001615. Results: In esophageal cancer, the expressions of hsa_circ_0001615 and miR-142-5p were increased and decreased, respectively. Hsa_circ_0001615 inhibition significantly reduced the proliferation, migration, and invasion but increased the apoptosis of esophageal cancer cells. Additionally, hsa_circ_0001615 knockdown increased miR-142-5p expression but decreased ß-catenin expression. MiR-142-5p was a direct target of hsa_circ_0001615. Conclusion: Hsa_circ_0001615 knockdown could mediate antitumor effects through the miR-142-5p/ß-catenin pathway.

Ensemble learning-assisted prediction of prolonged hospital length of stay after spine correction surgery: a multi-center cohort study.

PURPOSE: This research aimed to develop a machine learning model to predict the potential risk of prolonged length of stay in hospital before operation, which can be used to strengthen patient management. METHODS: Patients who underwent posterior spinal deformity surgery (PSDS) from eleven medical institutions in China between 2015 and 2022 were included. Detailed preoperative patient data, including demographics, medical history, comorbidities, preoperative laboratory results, and surgery details, were collected from their electronic medical records. The cohort was randomly divided into a training dataset and a validation dataset with a ratio of 70:30. Based on Boruta algorithm, nine different machine learning algorithms and a stack ensemble model were trained after hyperparameters tuning visualization and evaluated on the area under the receiver operating characteristic curve (AUROC), precision-recall curve, calibration, and decision curve analysis. Visualization of Shapley Additive exPlanations method finally contributed to explaining model prediction. RESULTS: Of the 162 included patients, the K Nearest Neighbors algorithm performed the best in the validation group compared with other machine learning models (yielding an AUROC of 0.8191 and PRAUC of 0.6175). The top five contributing variables were the preoperative hemoglobin, height, body mass index, age, and preoperative white blood cells. A web-based calculator was further developed to improve the predictive model's clinical operability. CONCLUSIONS: Our study established and validated a clinical predictive model for prolonged postoperative hospitalization duration in patients who underwent PSDS, which offered valuable prognostic information for preoperative planning and postoperative care for clinicians. Trial registration ClinicalTrials.gov identifier NCT05867732, retrospectively registered May 22, 2023, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05867732 .

Puerarin prevents sepsis-associated encephalopathy by regulating the AKT1 pathway in microglia.

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.

Primary intraosseous Rosai-Dorfman disease: An analysis of clinicopathologic characteristics, molecular genetics, and prognostic features.

Background: Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of uncertain pathogenesis. Most patients present with proliferation in the lymph nodes manifesting as adenopathy; however, RDD may primarily arise in a variety of extranodal sites, including the bone, which is a great challenge in the diagnosis. The clinicopathological characteristics and prognostic features of primary intraosseous RDD have not been well characterized. Methods: We retrospectively analyzed the clinicopathologic and prognostic features of four cases of primary intraosseous RDD during the past 10 years in our hospital, with a review of an additional 62 cases with complete follow-up data from the literature. Results: Primary intraosseous RDD was identified in 0.14% (4/2,800) of total bone biopsies performed at our institution over the study period. According to our retrospective analysis, a total of 18 cases of primary lymph node, skin, or other non-osseous site-based RDD were diagnosed in our hospital. The ages of the 66 total patients ranged from 1.5 to 76 years, with a median age of 25 years. There were 31 male and 35 female patients, with a male-to-female ratio of 0.89:1. Primary intraosseous RDD occurred most often in the bones of the extremities (60.6%, 40/66), with the proximal tibia being the most common location; 39.4% (26/66) of the cases arose in the axial skeleton, predominantly in the vertebra and craniofacial bones. Solitary masses and multiple tumors were present in 84.8% (56/66) and 15.2% (10/66) of the cases, respectively. Pain of the affected area was the most common presenting symptom. Radiographically, the lesions were lytic with well-defined and usually sclerotic margins. Immunohistochemistry showed that large histiocytes from patients with RDD were positive for OCT2, in addition to S100 and CD68. Molecular tests were performed in seven reported cases and four of our cases. All the 11 cases were non-decalcified. PCR results showed that there were no BRAF-V600E, KRAS, or NRAS mutations in primary intraosseous RDD; only one case with both RDD and Langerhans cell histiocytosis showed BRAF-V600E mutation. The survival data showed that 22.7% (15/66) of the patients experienced recurrences or developed RDD at distant sites during the follow-up period (median follow-up, 13 months; range, 1-106 months). The 5-year progression-free survival (PFS) of the patients with primary intraosseous RDD was 57.5%. We found that there was a significant difference in PFS between female and male patients (p = 0.031). However, there was no statistically significant difference in PFS between patients with solitary masses and multiple tumors (p = 0.698). Similarly, no statistically significant differences in PFS were found between the different age groups (p = 0.908) or tumor locations (p = 0.728). Conclusion: Primary intraosseous RDD is an extremely rare disease. The diagnosis of RDD may be quite challenging because of its non-specific clinical presentation and imaging. Immunohistochemistry showed that large histiocytes were positive for OCT2 in addition to S100 and CD68, which may be helpful for differential diagnosis. Molecular detection showed that RDD may be related to the MAPK pathway, though these results are also ultimately not specific. The pathogenesis of RDD is yet to be elucidated, but recent studies suggest possible clonality of hyperproliferative histiocytes.

Are preoperative phase-contrast CSF flow parameters ideal for predicting the outcome of shunt surgery in patients with idiopathic normal pressure hydrocephalus?

Purpose: Phase-contrast magnetic resonance (PC-MR) is widely used in patients with idiopathic normal pressure hydrocephalus (iNPH), but its role in predicting prognosis remains controversial. To evaluate the effectiveness of preoperative PC-MR CSF flow measurement in predicting the clinical response to shunt surgery in patients with iNPH. Methods: Forty-six patients with definite iNPH were included between January 2018 and January 2022. PC-MR was used to evaluate CSF peak velocity (PV), average velocity, aqueductal stroke volume (ASV), net ASV, and net flow. The modified Rankin Scale (mRS), iNPH grading scale (iNPHGS), Mini-Mental State Examination (MMSE), and Timed 3-m Up and Go Test (TUG) were used for clinical assessment. The primary endpoint was the improvement in the mRS score 1 year after surgery, and the secondary endpoints were the iNPHGS, MMSE, and TUG scores at 1 year. Differences between shunt improvement and non-improvement groups, based on the clinical outcomes, were compared using the Mann-Whitney U-test, logistic regression models, and receiver operating characteristic curves. Correlations between CSF flow parameters and the baseline clinical outcomes were assessed using Spearman's correlation coefficient. Results: No CSF parameters significantly differed between shunt improvement and non-improvement groups based on mRS and secondary outcomes. And all CSF parameters showed significant overlap in both shunt improvement and non-improvement groups based on mRS and secondary outcomes. Significant correlations between the mRS and iNPHGS scores, and PV, ASV, and net ASV were observed. Conclusion: While some preoperative PC-MR CSF flow parameters reflected the symptom severity of iNPH to a certain extent, they alone might not be ideal markers of shunt responsiveness.