The efficacy of suprapatellar, parapatellar and infrapatellar intramedullary nailing in the treatment of tibial fractures: a systematic review and meta-analysis.

BACKGROUND: Tibial fractures are common and challenging orthopedic injuries that are commonly treated with intramedullary nailing techniques via suprapatellar (SP), parapatellar (PP), and infrapatellar (IP) approaches. This study aimed to provide a comprehensive comparative analysis of the efficacy of different treatment approaches based on clinical outcomes. METHODS: We conducted a detailed search in PubMed, Cochrane Library, Embase, and Web of Science for clinical studies comparing suprapatellar, parapatellar, and infrapatellar approaches in intramedullary nailing of tibial fractures. Inclusion criteria included randomized controlled trials and retrospective cohort studies involving patients aged 18 and older, comparing outcomes of these surgical techniques. Exclusion criteria included studies with insufficient data, non-English publications, and those focusing on non-tibial fractures. RESULTS: A total of 15 studies involving 1396 patients were included in meta-analysis. Pooled results indicated that, compared to IP nailing, the SP approach significantly reduced fluoroscopy time (MD = - 35.63, 95% CI - 39.37 to - 31.89, p < 0.001), operative time (MD = - 10.72, 95% CI - 17.30 to - 4.15, p = 0.001), pain scores (SMD = - 1.49, 95% CI - 2.36 to - 0.62, p < 0.001), and improved Lysholm scores (MD = 5.74, 95% CI 3.29 to 8.19, p < 0.001) and malalignment rate (RR = 0.24, 95% CI 0.08 to 0.68, p = 0.008). Quality of life assessments also indicated higher physical component scores for the SP group (MD = 6.68, 95% CI 5.19 to 8.17, p < 0.001). CONCLUSION: The SP approach provides significant intraoperative and postoperative benefits, reducing surgery time and improving patient outcomes in pain management and knee joint function. These findings support the SP approach as a preferred option for surgical treatment of tibial fractures.

Prediction of epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma patients on computed tomography (CT) images using 3-dimensional (3D) convolutional neural network.

Background: Noninvasively detecting epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma patients before targeted therapy remains a challenge. This study aimed to develop a 3-dimensional (3D) convolutional neural network (CNN)-based deep learning model to predict EGFR mutation status using computed tomography (CT) images. Methods: We retrospectively collected 660 patients from 2 large medical centers. The patients were divided into training (n=528) and external test (n=132) sets according to hospital source. The CNN model was trained in a supervised end-to-end manner, and its performance was evaluated using an external test set. To compare the performance of the CNN model, we constructed 1 clinical and 3 radiomics models. Furthermore, we constructed a comprehensive model combining the highest-performing radiomics and CNN models. The receiver operating characteristic (ROC) curves were used as primary measures of performance for each model. Delong test was used to compare performance differences between different models. Results: Compared with the clinical [training set, area under the curve (AUC) =69.6%, 95% confidence interval (CI), 0.661-0.732; test set, AUC =68.4%, 95% CI, 0.609-0.752] and the highest-performing radiomics models (training set, AUC =84.3%, 95% CI, 0.812-0.873; test set, AUC =72.4%, 95% CI, 0.653-0.794) models, the CNN model (training set, AUC =94.3%, 95% CI, 0.920-0.961; test set, AUC =94.7%, 95% CI, 0.894-0.978) had significantly better predictive performance for predicting EGFR mutation status. In addition, compared with the comprehensive model (training set, AUC =95.7%, 95% CI, 0.942-0.971; test set, AUC =87.4%, 95% CI, 0.820-0.924), the CNN model had better stability. Conclusions: The CNN model has excellent performance in non-invasively predicting EGFR mutation status in patients with lung adenocarcinoma and is expected to become an auxiliary tool for clinicians.

Highly Sensitive Room-Temperature Detection of Ammonia in the Breath of Kidney Disease Patients Using Fe2Mo3O8/MoO2@MoS2 Nanocomposite Gas Sensor.

A novel Fe2Mo3O8/MoO2@MoS2 nanocomposite is synthesized for extremely sensitive detection of NH3 in the breath of kidney disease patients at room temperature. Compared to MoS2, α-Fe2O3/MoS2, and MoO2@MoS2, it shows the optimal gas-sensing performance by optimizing the formation of Fe2Mo3O8 at 900 °C. The annealed Fe2Mo3O8/MoO2@MoS2 nanocomposite (Fe2Mo3O8/MoO2@MoS2-900 °C) sensor demonstrates a remarkably high selectivity of NH3 with a response of 875% to 30 ppm NH3 and an ultralow detection limit of 3.7 ppb. This sensor demonstrates excellent linearity, repeatability, and long-term stability. Furthermore, it effectively differentiates between patients at varying stages of kidney disease through quantitative NH3 measurements. The sensing mechanism is elucidated through the analysis of alterations in X-ray photoelectron spectroscopy (XPS) signals, which is supported by density functional theory (DFT) calculations illustrating the NH3 adsorption and oxidation pathways and their effects on charge transfer, resulting in the conductivity change as the sensing signal. The excellent performance is mainly attributed to the heterojunction among MoS2, MoO2, and Fe2Mo3O8 and the exceptional adsorption and catalytic activity of Fe2Mo3O8/MoO2@MoS2-900 °C for NH3. This research presents a promising new material optimized for detecting NH3 in exhaled breath and a new strategy for the early diagnosis and management of kidney disease.

An investigation of tomosynthesis on the diagnostic efficacy of spot compression mammography.

To explore the diagnostic efficacy of tomosynthesis spot compression (TSC) compared with conventional spot compression (CSC) for ambiguous findings on full-field digital mammography (FFDM). In this retrospective study, 122 patients (including 108 patients with dense breasts) with ambiguous FFDM findings were imaged with both CSC and TSC. Two radiologists independently reviewed the images and evaluated lesions using the Breast Imaging Reporting and Data System. Pathology or at least a 1-year follow-up imaging was used as the reference standard. Diagnostic efficacies of CSC and TSC were compared, including area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The mean glandular dose was recorded and compared for TSC and CSC. Of the 122 patients, 63 had benign lesions and 59 had malignant lesions. For Reader 1, the following diagnostic efficacies of TSC were significantly higher than those of CSC: AUC (0.988 vs. 0.906, P = 0.001), accuracy (93.4% vs. 77.8%, P = 0.001), specificity (87.3% vs. 63.5%, P = 0.002), PPV (88.1% vs. 70.5%, P = 0.010), and NPV (100% vs. 90.9%, P = 0.029). For Reader 2, TSC showed higher AUC (0.949 vs. 0.909, P = 0.011) and accuracy (83.6% vs. 71.3%, P = 0.022) than CSC. The mean glandular dose of TSC was higher than that of CSC (1.85 ± 0.53 vs. 1.47 ± 0.58 mGy, P < 0.001) but remained within the safety limit. TSC provides better diagnostic efficacy with a slightly higher but tolerable radiation dose than CSC. Therefore, TSC may be a candidate modality for patients with ambiguous findings on FFDM.

The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

Using Multi-phase CT Radiomics Features to Predict EGFR Mutation Status in Lung Adenocarcinoma Patients.

RATIONALE AND OBJECTIVES: This study aimed to non-invasively predict epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma using multi-phase computed tomography (CT) radiomics features. MATERIALS AND METHODS: A total of 424 patients with lung adenocarcinoma were recruited from two hospitals who underwent preoperative non-enhanced CT (NE-CT) and enhanced CT (including arterial phase CT [AP-CT], and venous phase CT [VP-CT]). Patients were divided into training (n = 297) and external validation (n = 127) cohorts according to hospital. Radiomics features were extracted from the NE-CT, AP-CT, and VP-CT images, respectively. The Wilcoxon test, correlation analysis, and simulated annealing were used for feature screening. A clinical model and eight radiomics models were established. Furthermore, a clinical-radiomics model was constructed by incorporating multi-phase CT features and clinical risk factors. Receiver operating characteristic curves were used to evaluate the predictive performance of the models. RESULTS: The predictive performance of multi-phase CT radiomics model (AUC of 0.925 [95% CI, 0.879-0.971] in the validation cohort) was higher than that of NE-CT, AP-CT, VP-CT, and clinical models (AUCs of 0.860 [95% CI,0.794-0.927], 0.792 [95% CI, 0.713-0.871], 0.753 [95% CI, 0.669-0.838], and 0.706 [95% CI, 0.620-0.791] in the validation cohort, respectively) (all P < 0.05). The predictive performance of the clinical-radiomics model (AUC of 0.927 [95% CI, 0.882-0.971] in the validation cohort) was comparable to that of multi-phase CT radiomics model (P > 0.05). CONCLUSION: Our multi-phase CT radiomics model showed good performance in identifying the EGFR mutation status in patients with lung adenocarcinoma, which may assist personalized treatment decisions.

Alveolar Bone Morphologic Predictors for Guided Bone Regeneration Outcome in Anterior Maxilla.

OBJECTIVES: This study aimed to explore the influence of alveolar bone morphologic variables on the outcome of guided bone regeneration (GBR) in the anterior maxilla region. METHODS: Twenty-eight patients who received single maxillary anterior tooth delayed implant placed simultaneously with GBR were recruited. Baseline data including age, gender, implant site, implant brand, and bone graft materials were recorded. The resorption rate of the grafted bone (RRGB), labial bone width at 0 mm, 2 mm, and 4 mm apical to the implant platform at Tn (LBW0Tn, LBW2Tn, LBW4Tn), implant angulation (IA), maximum bone graft thickness (MBGT), bone graft volume (BGV), and the initial bone morphologic variables bone concavity depth (BCD) and bone concavity angulation (BCA) were measured. The Pearson correlation analysis, analysis of variance (ANOVA), and optimal binning method were used to explore the potential predictors for GBR. RESULTS: Among 28 patients, the labial bone width of implant and bone graft volume decreased significantly when measured 6 months after surgery. The mean percentage of RRGB was 49.78%. RRGB was not correlated with gender, age, bone graft material, IA, MBGT, bone graft volume at T1, implant site, and implant brand (P > .05). BCD and BCA were each moderately correlated with RRGB (r = -0.872 [P < .001] and r = 0.686 [P < .001], respectively). A BCD ≥1.03 mm and a BCA <155.30° resulted in a significantly lower percentage of RRGB (P < .001). CONCLUSIONS: A significant grafted bone materials volume reduction was detected after GBR with collagen membrane and deproteinized bovine bone mineral (DBBM). The initial bone morphology can influence GBR outcome, and a bone concavity with a depth ≥1.03 mm and an angulation <155.30° led to a lower RRGB. BCD and BCA can be used as variables to predict the outcome of GBR.

Preoperative prediction of microvascular invasion in hepatocellular carcinoma using ultrasound features including elasticity.

BACKGROUND: Microvascular invasion (MVI) is an important predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy. Shear wave elastography (SWE) plays an important role in hepatic imaging, but its value in the preoperative prediction of MVI in HCC has not yet been proven. AIM: To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC. METHODS: Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study. Conventional ultrasound features and SWE features such as maximal elasticity (Emax) of HCCs and Emax of the periphery of HCCs were acquired before surgery. These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs. RESULTS: This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs, including 54 with mild MVI and 48 with severe MVI. Maximal tumor diameters, surrounding liver tissue, color Doppler flow, Emax of HCCs, and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs. In addition, Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs. Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI, with odds ratios of 2.820 and 1.021, respectively. CONCLUSION: HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI. Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.

Studies of Dopamine Oxidation Process by Atmospheric Pressure Glow Discharge Mass Spectrometry.

An atmospheric pressure glow discharge ionisation source was constructed and utilized to study the dopamine (DA) oxidation process coupling with mass spectrometry. During the DA oxidation process catalysed by polyphenol oxidase (PPO), six cationic intermediates were directly detected by the atmospheric pressure glow discharge mass spectrometry (APGD-MS). Combined with tandem mass spectrometry, the structures of the dopamine o-semiquinone radical (DASQ) and leukodopaminochrome radical (LDAC●) intermediates and structures of the isomers of dopaminochrome (DAC) and 5,6-dihydroxyindole (DHI) were further characterised with the introduction of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) and deuterium oxide (D2O) to APGD-MS. Meanwhile, UV-Vis studies confirmed the important role of PPO in catalyzing the DA oxidation reaction. Based on APGD-MS studies, a possible mechanism could be proposed for DA oxidation catalysed by PPO. Furthermore, APGD-MS could provide possibilities for the effective detection and characterisation of short-lived intermediates, even in complicated systems.

Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat: How Does the Brain Breathe?

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.

Neoadjuvant Immunotherapy Combined with Chemotherapy for Local Advanced Non-Small-Cell Lung Cancer in a Patient with a History of Breast Cancer: A Case Report.

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1-2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy.

CNPY4 is a potential promising prognostic-related biomarker and correlated with immune infiltrates in gliomas.

Glioblastomas are classified into primary and secondary; primary glioblastomas develop rapidly and aggressively, whereas secondary glioblastomas are more common in grade II and III gliomas. Here, we aimed to demonstrate the role of the CNPY4 gene as a potential biomarker in immune infiltration in gliomas. Based on gene expression profile interaction analysis (GEPIA), we studied the survival model of CNPY4 and evaluated its effect on patients with glioma. The glioma dataset was downloaded from The Cancer Genome Atlas (TCGA) database. Logistic regression was used to analyze the relationship between clinical data and CNPY4 expression. Univariate and multivariate Cox proportional-hazards models were used to compare clinical features and patient survival. The relationship between CNPY4 and immune infiltration in glioma was studied using GEPIA and CIBERSORT online tools. TCGA data were analyzed using gene set enrichment analysis (GSEA). Finally, TIMER was used to analyze the expression and immune infiltration of CNPY4 in glioma to study the cumulative survival rate. Univariate logistic regression analysis showed that increased CNPY4 expression was associated with tumor age, grade, IDH status, and 1p/19q codeletion. Multivariate analysis showed that that downregulation of CNPY4 expression was an independent and satisfactory prognostic factor. CNPY4 expression was correlated with the infiltration level of dendritic cells in glioblastoma. In contrast, in low-grade gliomas, the infiltration level of B cells, dendritic cells, macrophages, neutrophils, and CD4+ T cells was significantly correlated with CNPY4 expression. The GSEA results showed that CNPY4 played an immunoregulatory role in immune-related phenotypic pathways between lymphoid and nonlymphoid cells. The intestinal immune networks for IgA production, rabbit thyroid disease, primary immunodeficiencies, and cancer immunotherapy were enriched by PD-1 blockade. High CNPY4 expression is a biomarker of glioma prognosis and is associated with the immune invasion of glioma.

Establishment and Validation of a Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Lower-Grade Glioma.

Background: The prognosis of lower-grade glioma (LGG) is highly variable, and more accurate predictors are still needed. The aim of our study was to explore the prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in LGG and to develop a novel risk signature for predicting survival with LGG. Methods: We first integrated multiple datasets to screen for prognostic ferroptosis-related lncRNAs in LGG. A least absolute shrinkage and selection operator (LASSO) analysis was then utilized to develop a risk signature for prognostic prediction. Based on the results of multivariate Cox analysis, a prognostic nomogram model for LGG was constructed. Finally, functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA), immunity, and m6A correlation analyses were conducted to explore the possible mechanisms by which these ferroptosis-related lncRNAs affect survival with LGG. Results: A total of 11 ferroptosis-related lncRNAs related to the prognosis of LGG were identified. Based on prognostic lncRNAs, a risk signature consisting of 8 lncRNAs was constructed and demonstrated good predictive performance in both the training and validation cohorts. Correlation analysis suggested that the risk signature was closely linked to clinical features. The nomogram model we constructed by combining the risk signature and clinical parameters proved to be more accurate in predicting the prognosis of LGG. In addition, there were differences in the levels of immune cell infiltration, immune-related functions, immune checkpoints, and m6A-related gene expression between the high- and low-risk groups. Conclusion: In summary, our ferroptosis-related lncRNA signature exhibits good performance in predicting the prognosis of LGG. This study may provide useful insight into the treatment of LGG.

Development of a Nomogram Based on 3D CT Radiomics Signature to Predict the Mutation Status of EGFR Molecular Subtypes in Lung Adenocarcinoma: A Multicenter Study.

Background: This study aimed to noninvasively predict the mutation status of epidermal growth factor receptor (EGFR) molecular subtype in lung adenocarcinoma based on CT radiomics features. Methods: In total, 728 patients with lung adenocarcinoma were included, and divided into three groups according to EGFR mutation subtypes. 1727 radiomics features were extracted from the three-dimensional images of each patient. Wilcoxon test, least absolute shrinkage and selection operator regression, and multiple logistic regression were used for feature selection. ROC curve was used to evaluate the predictive performance of the model. Nomogram was constructed by combining radiomics features and clinical risk factors. Calibration curve was used to evaluate the goodness of fit of the model. Decision curve analysis was used to evaluate the clinical applicability of the model. Results: There were three, two, and one clinical factor and fourteen, thirteen, and four radiomics features, respectively, which were significantly related to each EGFR molecular subtype. Compared with the clinical and radiomics models, the combined model had the highest predictive performance in predicting EGFR molecular subtypes [Del-19 mutation vs. wild-type, AUC=0.838 (95% CI, 0.799-0.877); L858R mutation vs. wild-type, AUC=0.855 (95% CI, 0.817-0.894); and Del-19 mutation vs. L858R mutation, AUC=0.906 (95% CI, 0.869-0.943), respectively], and it has a stable performance in the validation set [AUC was 0.813 (95% CI, 0.740-0.886), 0.852 (95% CI, 0.790-0.913), and 0.875 (95% CI, 0.781-0.929), respectively]. Conclusion: Our combined model showed good performance in predicting EGFR molecular subtypes in patients with lung adenocarcinoma. This model can be applied to patients with lung adenocarcinoma.

NGF/TrkA promotes the vitality, migration and adhesion of bone marrow stromal cells in hypoxia by regulating the Nrf2 pathway.

BACKGROUND: Bone marrow stromal cells (BMSCs) transplantation is a treatment strategy for ischemic stroke (IS) with great potential. However, the vitality, migration and adhesion of BMSCs are greatly impaired due to the harsh environment of the ischemic area, which affects the therapeutic effects. Herein, we aimed to investigate the roles of nerve growth factor (NGF) in regulating cell behaviors of BMSCs in IS. METHODS: The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. To simulate ischemic-like conditions in vitro, Brain microvascular (bEnd.3) cells were exposed to oxygen and glucose deprivation (OGD). Cell viability and cell proliferation were evaluated by MTT assay and BrdU assay, respectively. Transwell migration and cell adhesion assays were carried out to determine cell migration and adhesion of BMSCs, respectively, coupled with flow cytometry to evaluate cell apoptosis of bEnd.3 cells. Finally, angiogenesis assay was performed to assess the angiogenesis ability of bEnd.3 cells. RESULTS: NGF overexpression resulted in increased cell vitality, adhesion and migration of BMSCs, while NGF knockdown presented the opposite effects. We subsequently discovered that TrkA was a receptor for NGF, and TrkA knockdown significantly inhibited the cell viability, migration and adhesion of BMSCs. Besides, Nrf2 was confirmed as the downstream target of NGF/TrkA to promote the viability, adhesion and migration of BMSC cells. Finally, NGF-silenced BMSCs could not effectively restore the OGD-induced brain microvascular cell damage. CONCLUSIONS: NGF/TrkA promoted the viability, migration and adhesion of BMSCs in IS via activating Nrf2 pathway.

Biological variation in the serum and urine kidney injury markers of a healthy population measured within 24 hours.

BACKGROUND AND AIMS: To explore the biological variation (BV) of kidney injury markers in serum and urine of healthy subjects within 24 hours to assist with interpretation of future studies using these biomarkers in the context of known BV. MATERIALS AND METHODS: Serum and urine samples were collected every 4 hours (0, 4, 8, 12, 16 and 20 hours) from 31 healthy subjects within 24 hours and serum creatinine (s-Crea), serum ß2-microglobin (s-ß2MG), serum cystatin C (s-CYSC), serum neutrophil gelatinase-associated lipoprotein (s-NGAL), urine creatinine (u-Crea), urine ß2-microglobin (u-ß2MG), urine cystatin C (u-CYSC), urine neutrophil gelatinase-associated lipoprotein (u-NGAL) were measured. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA analysis on trend-corrected data (if relevant), and analytical (CVA), within-subject (CVI), and between-subject (CVG) biological variation were calculated. RESULTS: The concentration of kidney injury markers in male was higher than that in female, except for u-CYSC and u-NGAL. There were no significant difference in serum and urine kidney injury markers concentration at different time points. Serum CVI was lower than urine CVI, serum CVG was higher than CVI, and urine CVG was lower than CVI. The individual index (II) of serum kidney injury markers was less than 0.6, while the II of urinary kidney injury markers was more than 1.0. CONCLUSIONS: This study provides new short-term BV data for kidney injury markers in healthy subjects within 24 hours, which are of great significance in explaining other AKI / CKD studies.

Removing a suprapatellar intramedullary nail via a suprapatellar approach: a retrospective cohort study.

BACKGROUND: Over the last 20 years, suprapatellar (SP) intramedullary nailing has gained considerable attention for treating tibia fractures and is believed to improve fracture alignments, decrease anterior knee pain, and facilitate intraoperative fluoroscopy. However, it is associated with various concerns, including the need to make another infrapatellar (IP) incision to remove the nail. AIMS: This study was aimed at developing a new technique for the removal of SP tibial nails through an SP approach using a cannulated extraction system. The efficiency of the novel SP approach was compared to that of the traditional IP approach for the removal of SP tibial nails. PATIENTS AND METHODS: This was a retrospective cohort study from a prospectively collected clinical registry. The data for 69 consecutive patients who received surgery to remove a previous SP intramedullary nail using an SP approach (n = 30, SP cohort) or an IP approach (n = 39, IP cohort) were analyzed. Intra-operative evaluations included intraoperative blood loss, operation time, and changes in the surgical procedures. At six months follow-up, post-operative Lysholm knee score, visual analog scale (VAS) score, and the active range of motion (ROM) of the affected knee and complications were assessed. RESULTS: Patients in the SP cohort exhibited an increased post-operative Lysholm knee score (ß, 2.6; 95% confidence interval [CI], 0.6 to 4.6; P = 0.012), decreased post-operative VAS score (ß, - 0.7; 95% CI, - 1.1 to - 0.2; P = 0.004), and increased operation time (ß, 9.8 minutes; 95% CI, 5.7 to 14.0 minutes; P < 0.001) compared with those treated with the IP approach after adjustment for baseline characteristics. There were no statistically significant differences in blood loss, post-operative ROM, or complications between the two cohorts. CONCLUSIONS: Compared with the IP technique, the SP approach for the removal of an SP tibial nail was independently associated with an increased post-operative Lysholm knee score and decreased VAS score, although the surgery was longer in duration. The novel technique offers a reliable and minimally invasive option for the removal of an SP tibial nail.

Comparison between infrapatellar and suprapatellar approaches for intramedullary nailing for the fractures of the tibial shaft.

INTRODUCTION: This study aimed to compare the outcomes at the clinical and functional levels of suprapatellar (SP) and infrapatellar (IP) approaches for intramedullary nailing in treating tibial shaft fracture. METHODS: Patients who underwent tibial shaft fracture intramedullary nailing by the SP approach or IP approach in a trauma center were retrospectively reviewed. The demographics, intraoperative fluoroscopy time, operation time, blood loss, irrigation volume, postoperative X-ray alignment, and complications of patients were compared between the two groups under different approaches. Lysholm knee score, visual analog score (VAS), and incidence of anterior knee pain (AKP) were assessed 1 year after surgery. RESULTS: The study finally included well-documented 81 patients (38 SP versus 43 IP). The SP group exhibited significantly shorter intraoperative fluoroscopy time than that of the IP group (81.7 ± 14.5 s vs. 122.0 ± 24.3 s, P < 0.001). Both aspects recorded a precise reduction of the fracture: angulation (2.1 ± 1.2° vs 3.1 ± 1.5°, P < 0.05) and translation (0.6 ± 0.8 mm vs 1.4 ± 1.5 mm, P < 0.05) in the coronal plane in the SP group. However, the sagittal plane recorded no such change (P > 0.05). The Lysholm knee score was higher in the SP group than that of the IP group (87 ± 8 vs. 80 ± 15, P < 0.05). The SP group displayed an evidently lower average VAS score than that of the IP approach group (0.3 ± 0.8 vs 1.3 ± 1.4, P < 0.001). Six cases (16%) in the SP group and 16 cases (37%) in the IP group experienced AKP 1-year post-operation (P < 0.05). As far as complications are concerned, neither group showed any significant difference (P > 0.05). CONCLUSION: Compared with the IP approach, the application of intramedullary nailing through the SP approach in treating tibial shaft fractures can effectively shorten the intraoperative fluoroscopy time, correct coronal plane angulation and translation deformity, reduce the incidence of AKP and improve postoperative function.