Exploitation of enhanced prime editing for blocking aberrant angiogenesis.

INTRODUCTION: Aberrant angiogenesis plays an important part in the development of a variety of human diseases including proliferative diabetic retinopathy, with which there are still numerous patients remaining a therapeutically challenging condition. Prime editing (PE) is a versatile gene editing approach, which offers a novel opportunity to genetically correct challenging disorders. OBJECTIVES: The goal of this study was to create a dominant-negative (DN) vascular endothelial growth factor receptor (VEGFR) 2 by editing genomic DNA with an advanced PE system to block aberrant retinal angiogenesis in a mouse model of oxygen-induced retinopathy. METHODS: An advanced PE system (referred to as PE6x) was established within two lentiviral vectors, with one carrying an enhanced PE guide RNA and a canonical Cas9 nickase fused with an optimized reversal transcriptase, and the other conveying a nicking guide RNA and a DN-MLH1 to improve PE efficiency. Dual non-integrating lentiviruses (NILVs) produced with the two lentiviral PE6x vectors were then employed to create a mutation of VEGFR2 T17967A by editing the Mus musculus VEGFR2 locus in vitro and in vivo, leading to generation of a premature stop codon (TAG, K796stop) to produce DN-VEGFR2, to interfere with the wild type VEGFR2 which is essential for angiogenesis. RESULTS: NILVs targeting VEGFR2 delivered into cultured murine vascular endothelial cells led to 51.06 % VEGFR2 T17967A in the genome analyzed by next generation sequencing and the production of DN-VEGFR2, which was found to hamper VEGF-induced VEGFR2 phosphorylation, as demonstrated by Western blot analysis. Intravitreally injection of the dual NILVs into postnatal day 12 mice in a model of oxygen-induced retinopathy, led to production of retinal DN-VEGFR2 in postnatal day 17 mice which blocked retinal VEGFR2 expression and activation as well as abnormal retinal angiogenesis without interfering with retinal structure and function, as assessed by electroretinography, optical coherence tomography, fundus fluorescein angiography and histology. CONCLUSION: DN-VEGFR2 resulted from editing genomic VEGFR2 using the PE6x system can be harnessed to treat intraocular pathological angiogenesis.

Intermittent protein restriction before but not after the onset of diabetic kidney disease attenuates disease progression in mice.

Background: High dietary protein intake exacerbates proteinuria in individuals with diabetic kidney disease (DKD). However, studies on the impacts of low protein diet (LPD) on DKD have yielded conflicting results. Furthermore, patient compliance to continuous protein restriction is challenging. Objective: The current study aims to investigate the effects of intermittent protein restriction (IPR) on disease progression of DKD. Methods: Diabetic KK-Ay mice were used in this study. For the IPR treatment, three consecutive days of LPD were followed by four consecutive days of normal protein diet (NPD) within each week. For early intervention, mice received IPR before DKD onset. For late intervention, mice received IPR after DKD onset. In both experiments, age-matched mice fed continuous NPD served as the control group. Kidney morphology, structure and function of mice in different groups were examined. Results: Intermittent protein restriction before DKD onset ameliorated pathological changes in kidney, including nephromegaly, glomerular hyperfiltration, tubular injuries and proteinuria, without improving glycemic control. Meanwhile, IPR initiated after DKD onset showed no renoprotective effects despite improved glucose homeostasis. Conclusion: Intermittent protein restriction before rather than after DKD onset protects kidneys, and the impacts of IPR on the kidneys are independent of glycemic control. IPR shows promise as an effective strategy for managing DKD and improving patient compliance.

Enhancing predictive validity of motoric cognitive risk syndrome for incident dementia and all-cause mortality with handgrip strength: insights from a prospective cohort study.

Background: This study aimed to assess whether integrating handgrip strength (HGS) into the concept of motoric cognitive risk (MCR) would enhance its predictive validity for incident dementia and all-cause mortality. Methods: A cohort of 5, 899 adults from the Health and Retirement Study underwent assessments of gait speed, subjective cognitive complaints, and HGS were involved. Over a 10-year follow-up, biennial cognitive tests and mortality data were collected. Cox proportional hazard analyses assessed the predictive power of MCR alone and MCR plus HGS for incident dementia and all-cause mortality. Results: Patients with MCR and impaired HGS (MCR-HGS) showed the highest adjusted hazard ratios (AHR) for dementia (2.33; 95% CI, 1.49-3.65) and mortality (1.52; 95% CI, 1.07-2.17). Even patients with MCR and normal HGS (MCR-non-HGS) experienced a 1.77-fold increased risk of incident dementia; however, this association was not significant when adjusted for socioeconomic status, lifestyle factors, and medical conditions. Nevertheless, all MCR groups demonstrated increased risks of all-cause mortality. The inclusion of HGS in the MCR models significantly improved predictive discrimination for both incident dementia and all-cause mortality, as indicated by improvements in the C-statistic, integrated discrimination improvement (IDI) and net reclassification indices (NRI). Conclusion: Our study underscores the incremental predictive value of adding HGS to the MCR concept for estimating risks of adverse health outcomes among older adults. A modified MCR, incorporating HGS, could serve as an effective screening tool during national health examinations for identifying individuals at risk of dementia and mortality.

Prognostic value of lung immune prognostic index in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a meta-analysis.

Background and Purpose: Until now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, the lung immune prognostic index (LIPI), has shown relatively high prognostic value in patients with solid cancer. Therefore, this study aimed to further identify the association between LIPI and the survival of patients with NSCLC who receive immune checkpoint inhibitors (ICIs). Methods: Several electronic databases were searched for available publications up to April 23, 2023. Immunotherapy outcomes included overall survival (OS), progression-free survival (PFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis based on the study design and comparison of the LIPI was conducted. Results: In this meta-analysis, 21 studies with 9,010 patients were included in this meta-analysis. The pooled results demonstrated that elevated LIPI was significantly associated with poor OS (HR = 2.50, 95% CI:2.09-2.99, p < 0.001) and PFS (HR = 1.77, 95% CI:1.64-1.91, p < 0.001). Subgroup analyses stratified by study design (retrospective vs. prospective) and comparison of LIPI (1 vs. 0, 2 vs. 0, 1-2 vs. 0, 2 vs. 1 vs. 0, 2 vs. 0-1 and 2 vs. 1) showed similar results. Conclusion: LIPI could serve as a novel and reliable prognostic factor in NSCLC treated with ICIs, and elevated LIPI predicts worse prognosis.

A nomogram combining CT-based radiomic features with clinical features for the differentiation of benign and malignant cystic pulmonary nodules.

BACKGROUND: Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules. METHODS: The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People's Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). RESULTS: A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804-0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application. CONCLUSION: In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.

Diagnostic performance of Node Reporting and Data System (Node-RADS) for assessing mesorectal lymph node in rectal cancer by CT.

BACKGROUND: To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment. METHODS: Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated. RESULTS: Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p < 0.001). For size-prioritized LN, Node-RADS achieved an AUC of 0.826, significantly superior to short-axis diameter (0.826 vs. 0.743, p = 0.009). For morphology-prioritized LN, Node-RADS exhibited an AUC of 0.758, slightly better than short-axis diameter (0.758 vs. 0.718, p = 0.098). The Node-RADS score of size-prioritized LN was significantly better than that of morphology-prioritized LN (0.826 vs. 0.758, p = 0.038). The nomogram achieved the best diagnostic performance (AUC = 0.861) than all the other assessment methods (p < 0.05). CONCLUSIONS: The Node-RADS scoring system outperforms the short-axis diameter in predicting lymph node metastasis in RC. Size-prioritized LN demonstrates superior predictive efficacy compared to morphology-prioritized LN. The nomogram combined the Node-RADS score of size-prioritized LN with clinical features exhibits the best diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.

Correlation between vertebral bone mineral density and multi-level virtual non-calcium imaging parameters from dual-layer spectral detector computed tomography.

Background: Virtual non-calcium (VNCa) imaging based on dual-energy computed tomography (CT) plays an increasingly important role in diagnosing spinal diseases. However, the utility of VNCa technology in the measurement of vertebral bone mineral density (BMD) is limited, especially the VNCa CT value at multiple calcium suppression levels and the slope of VNCa curve. This retrospective cross-sectional study aimed to explore the correlation between vertebral BMD and new VNCa parameters from dual-layer spectral detector CT. Methods: The dual-layer spectral detector CT and quantitative CT (QCT) data of 4 hydroxyapatite (HAP) inserts and 667 vertebrae of 234 patients (132 male and 102 female) who visited a university teaching hospital between April and May 2023 were retrospectively analyzed. The BMD values of 3 vertebrae (T12, L1, and L2) and inserts were measured using QCT, defined as QCT-BMD. The VNCa CT values and the slope λ of the VNCa attenuation curve of vertebrae and inserts were recorded. The correlations between VNCa parameters (VNCa CT value, slope λ) and QCT-BMD were analyzed. Results: For the vertebrae, the correlation coefficient ranged from -0.904 to 0.712 (all P<0.05). As the calcium suppression index (CaSI) increased, the correlation degree exhibited a decrease first and then increased, with the best correlation (r=-0.904, P<0.001) observed at the index of 25%. In contrast, the correlation coefficient for the inserts remained relatively stable (r=-0.899 to -1, all P<0.05). For the vertebrae, the values of 3 slopes λ (λ1, λ2, and λ3) derived from the VNCa attenuation curve were 6.50±1.99, 3.75±1.15, and 2.04±0.62, respectively. Regarding the inserts, the λ1, λ2, and λ3 values were 11.56 [interquartile range (IQR): 2.40-22.62], 6.68 (IQR: 1.39-13.49), and 3.63 (IQR: 0.75-7.8), respectively. For the vertebrae, all 3 correlation coefficients between 3 slopes λ and QCT-BMD were 0.956 (all P<0.05). For the inserts, the 3 correlation coefficients were 0.996, 0.998, and 1 (all P<0.05), respectively. Conclusions: A promising correlation was detected between VNCa CT parameters and QCT-BMD in vertebrae, warranting further investigation to explore the possibility of VNCa imaging to assess BMD.

Establishment of the Diagnostic Signature of Ferroptosis Genes in Multiple Sclerosis.

Ferroptosis is a novel form of membrane-dependent cell death that differs from other cell death modalities such as necrosis, apoptosis, and autophagy. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system primarily affecting brain and spinal cord neurons. Although the pathogenesis of these two conditions may seem unrelated, recent studies have indicated a connection between ferroptosis and multiple sclerosis. In fact, ferroptosis plays a significant role in the development of MS, as evidenced by the presence of elevated iron levels and iron metabolism abnormalities in the brains, spinal cords, and other neurons of MS patients. These abnormalities disrupt iron homeostasis within cells, leading to the occurrence of ferroptosis. However, there is currently a lack of research on the diagnostic value of ferroptosis-related genes in multiple sclerosis. In this study, we employed bioinformatics methods to identify ferroptosis-related genes (ATM, GSK3B, HMGCR, KLF2, MAPK1, NFE2L1, NRAS, PCBP1, PIK3CA, RPL8, VDAC3) associated with the diagnosis of multiple sclerosis and constructed a diagnostic model. The results demonstrated that the diagnostic model accurately identified the patients' condition. Subsequently, subgroup analysis was performed based on the expression levels of ferroptosis-related genes, dividing patients into high and low expression groups. The results showed differences in immune function and immune cell infiltration between the two groups. Our study not only confirms the correlation between ferroptosis and multiple sclerosis but also demonstrates the diagnostic value of ferroptosis-related genes in the disease. This provides guidance for clinical practice and direction for further mechanistic research.

Export priority technique for Uni-portal thoracoscopic left upper lobectomy.

BACKGROUND: Further explore the safety and feasibility of Uni-portal video assisted thoracoscopic (UVATS) left upper lobectomy by optimizing the treatment of incisions and blood vessels. METHODS: We conducted a retrospective analysis of data from 32 patients who underwent UVATS left upper lobectomy and systematic mediastinal lymph node dissection utilizing the Export priority technique between January 2021 and December 2022. We documented perioperative indicators, including surgical time, intraoperative blood loss, the number of lymph nodes dissected, and postoperative pathological staging. RESULTS: All surgeries were conducted utilizing the Export priority technique in UVATS. The mean surgical duration was (98.93 ± 14.98) minutes, with an average intraoperative blood loss of (79.53 ± 37.96) ml. The mean count of dissected lymph nodes was (13.96 ± 2.69). The length of hospital Stay averaged (5.62 ± 1.81) days. On the first postoperative day, the thoracic drainage volume was (101.87 ± 49.46) ml. The mean duration of postoperative thoracic tube insertion was (3.1 ± 1.84) days. No occurrences of postoperative hoarseness, pulmonary infection, or complications such as bronchopleural fistula were observed. CONCLUSION: The application of the Export priority technique improves the safety and feasibility of UVATS left upper lobectomy.

Comparative Analysis of the Anti-Inflammatory Effects of Liraglutide and Dulaglutide.

Inflammation plays a pathophysiological role in atherosclerosis and its clinical consequences. In addition to glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are of wide concern for cardioprotective effects. The structure, half-life, homology, and clinical efficacy of GLP-1RAs exhibit remarkable disparity. Several studies have compared the disparities in anti-inflammatory effects between daily and weekly GLP-1RAs. This study aimed to compare the similarities and differences between liraglutide and dulaglutide in terms of inhibiting atherosclerotic inflammation and improving co-cultured endothelial cell function. The expression of inflammation markers was examined by immunofluorescence, Western blotting, and real-time PCR. The tube-forming ability of endothelial cells was tested on Matrigel. The results verify that 10/50/100 nmol/L liraglutide and 100 nmol/L dulaglutide markedly suppressed the expression of inflammatory factors in LPS-induced atherosclerosis after 24 and 72 hours, respectively. Moreover, they promoted the polarization of M1 macrophages toward the M2 phenotype and improved the function of co-cultured endothelial cells. Both liraglutide and dulaglutide ameliorate atherosclerosis development. The difference between the two resided in the extended intervention duration required to observe the effect of dulaglutide, and liraglutide demonstrated a superior dose-dependent manner. We provide a potential strategy to understand the dynamics of drug action and possible timing administration.

Effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange compared with standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: A meta-analysis based on randomized controlled trials.

PURPOSE: To further identify the effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) for pre- and apneic oxygenation during the anesthesia induction by comparison to facemask ventilation (FMV) based on current available evidence. METHODS: Medline, EMBASE, Web of Science, Cochrane Library and CNKI databases were searched from inception to December 22, 2023 for available randomized controlled trials (RCTs). Primary outcomes were PaO2 and PaCO2 after intubation and safe apnoea time. Secondary outcomes included the O2 desaturation, end expiratory carbon dioxide (EtCO2) and complications. The effect measures for continuous and categorical outcomes were separately the mean difference (MD) and relative risk (RR) with 95% confidence interval. RESULTS: Twelve RCTs with 403 patients in the THRIVE group and 401 patients in th FMV group were included. Pooled results demonstrated that the PaO2 after intubation was significantly higher (MD = 82.90mmHg, 95% CI: 12.25~153.54mmHg, P = 0.02) and safe apnoea time (MD = 103.81s, 95% CI: 42.07~165.56s, P = 0.001) was longer in the THRIVE group. Besides, the incidence rate of O2 desaturation (RR = 0.28, 95% CI: 0.12-0.66, P = 0.004) and gastric insufflation (RR = 0.26, 95% CI: 0.13-0.49, P<0.001) was significantly lower in the THRIVE group. CONCLUSION: Based on current evidence, THRIVE manifested better effectiveness representing as improved oxygenation, prolonged safe apnoea time and decreased risk of complications compared to standard FMV in surgical patients. Therefore, THRIVE could be served as a novel and valuable oxygenation technology for patients during anesthesia induction.

Prognostic role of lymph node micrometastasis in pN0 esophageal cancer: A meta-analysis.

BACKGROUND: To further identify the association between the lymph node micrometastasis (LNM) and long-term survival among pN0 esophageal cancer patients receiving the surgery. METHODS: Several databases were searched for relevant studies up to June 22, 2023. The primary and secondary outcomes were separately overall survival (OS) and relapse-free survival (RFS) and hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Subgroup analysis based on pathological type and source of HR was further performed. All statistical analyses were conducted by STATA 15.0 software. RESULTS: A total of 20 studies involving 1830 pN0 patients were included in this meta-analysis. The pooled results demonstrated that the presence of LNM indicated significantly worse OS (HR = 2.19, 95% CI = 1.77-2.70, P < .001) and RFS (HR = 2.15, 95% CI = 1.65-2.80, P < .001). Besides, subgroup analysis for the OS and RFS stratified by the pathological type (squamous cell carcinoma vs mixed esophageal cancer) and source of HR (reported vs estimated) further identified the significant relationship of LNM with prognosis in surgical esophageal cancer. CONCLUSION: The presence of LNM indicated significantly poorer long-term survival among operated pN0 esophageal cancer patients. LNM could serve as a novel and reliable prognostic indicator in surgical esophageal cancer.

Identification and validation of a novel nine-gene prognostic signature of stem cell characteristic in hepatocellular carcinoma.

Currently, cancer stem cells (CSCs) are regarded as the most promising target for cancer therapy due to their close association with tumor resistance, invasion, and recurrence. Thus, identifying CSCs-related genes and constructing a prognostic risk model associated with CSCs may be crucial for hepatocellular carcinoma (HCC) therapy. Xena Browser was used to download gene expression profiles and clinical data, while MSigDB was used to obtain genes associated with CSCs. Firstly, the non-negative matrix factorization (NMF) algorithm was used to cluster the HCC samples based on CSCs-related genes. To evaluate the predictive performance of the risk model, the receiver operating characteristic curves (ROC) and Kaplan-Meier analysis were used. The R package "rms" was used to construct the final nomogram based on risk scores and clinical characteristics. Based on 449 CSCs-related genes, a total of 588 HCC samples from TCGA-LIHC and ICGC-LIRI_JP were classified into four molecular subtypes with marked differences in survival and mRNA stemness index (mRNAsi) between subtypes. Univariate Cox regression, multivariate Cox regression, and LASSO regression analyses were performed on a total of 1417 differentially expressed genes (DEGs) between subtypes, and a nine-gene prognostic model was constructed with TTK, ST6GALNAC4, SPP1, SGCB, MEP1A, HTRA1, CD79A, C6, and ATP2A3. In both the training and testing sets and the external validation cohort, the risk model performed well in predicting HCC patients' survival. A nomogram was constructed and had high predictive efficacy in short-term survival. In comparison with the other two prognostic models, our nine-gene signature model performed best. We constructed a nine-gene signature model to predict the survival of HCC patients, which has good predictive efficacy and stability. The model may contribute to guiding the prognostic assessment of HCC patients in clinical practice.

FXR/Menin-mediated epigenetic regulation of E2F3 expression controls ß-cell proliferation and is increased in islets from diabetic GK rats after RYGB.

Farnesoid X receptor (FXR) improves the function of islets, especially in the setting of Roux-en-Y gastric bypass (RYGB). Here we investigated how FXR activation regulates ß-cell proliferation and explored the potential link between FXR signaling and the menin pathway in controlling E2F3 expression, a key transcription factor for controlling adult ß-cell proliferation. Stimulation with the FXR agonist GW4064 or chenodeoxycholic acid (CDCA) increased E2F3 expression and ß-cell proliferation. Consistently, E2F3 knockdown abolished GW4064-induced proliferation. Treatment with GW4064 increased E2F3 expression in ß-cells via enhancing Steroid receptor coactivator-1 (SRC1) recruitment, increasing the pro-transcriptional acetylation of histone H3 at the E2f3 promoter. GW4064 treatment also decreased the association between FXR and menin, leading to the induction of FXR-mediated SRC1 recruitment. Mimicking the impact of FXR agonists, RYGB also increased E2F3 expression and ß-cell proliferation in GK rats and SD rats. These findings unravel the crucial role of the FXR/menin signaling in epigenetically controlling E2F3 expression and ß-cell proliferation, a mechanism possibly underlying RYGB-induced ß-cell proliferation.

CT-based radiomics for differentiating peripherally located pulmonary sclerosing pneumocytoma from carcinoid.

BACKGROUND: Pulmonary sclerosing pneumocytoma (PSP) and pulmonary carcinoid (PC) are difficult to distinguish based on conventional imaging examinations. In recent years, radiomics has been used to discriminate benign from malignant pulmonary lesions. However, the value of radiomics based on computed tomography (CT) images to differentiate PSP from PC has not been well explored. PURPOSE: We aimed to investigate the feasibility of radiomics in the differentiation between PSP and PC. METHODS: Fifty-three PSP and fifty-five PC were retrospectively enrolled and then were randomly divided into the training and test sets. Univariate and multivariable logistic analyses were carried to select clinical predictor related to differential diagnosis of PSP and PC. A total of 1316 radiomics features were extracted from the unenhanced CT (UECT) and contrast-enhanced CT (CECT) images, respectively. The minimum redundancy maximum relevance and the least absolute shrinkage and selection operator were used to select the most significant radiomics features to construct radiomics models. The clinical predictor and radiomics features were integrated to develop combined models. Two senior radiologists independently categorized each patient into PSP or PC group based on traditional CT method. The performances of clinical, radiomics, and combined models in differentiating PSP from PC were investigated by the receiver operating characteristic (ROC) curve. The diagnostic performance was also compared between the combined models and radiologists. RESULTS: In regard to differentiating PSP from PC, the area under the curves (AUCs) of the clinical, radiomics, and combined models were 0.87, 0.96, and 0.99 in the training set UECT, and were 0.87, 0.97, and 0.98 in the training set CECT, respectively. The AUCs of the clinical, radiomics, and combined models were 0.84, 0.92, and 0.97 in the test set UECT, and were 0.84, 0.93, and 0.98 in the test set CECT, respectively. In regard to the differentiation between PSP and PC, the combined model was comparable to the radiomics model, but outperformed the clinical model and the two radiologists, whether in the test set UECT or CECT. CONCLUSIONS: Radiomics approaches show promise in distinguishing between PSP and PC. Moreover, the integration of clinical predictor (gender) has the potential to enhance the diagnostic performance even further.

Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China.

BACKGROUND: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. METHODS: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. FINDINGS: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. CONCLUSIONS: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.

The possible neural mechanism of neuropathic pain evoked by motor imagery in pediatric patients with complete spinal cord injury: A preliminary brain structure study based on VBM.

In this study, we observed pediatric complete spinal cord injury (CSCI) patients receiving MI training and divided them into different groups according to the effect of motor imagery (MI) training on neuropathic pain (NP). Then, we retrospectively analysed the differences in brain structure of these groups before the MI training, identifying brain regions that may predict the effect of MI on NP. Thirty pediatric CSCI patients were included, including 12 patients who experienced NP during MI and 18 patients who did not experience NP during MI according to the MI training follow-up. The 3D high-resolution T1-weighted images of all subjects were obtained using a 3.0 T MRI system before MI training. A two-sample t-test was performed to evaluate the differences in gray matter volume (GMV) between patients who experienced NP and those who did not experience NP during MI. Receiver operating characteristic (ROC) analysis was performed to compute the sensitivity and specificity of the imaging biomarkers for the effect of MI on NP in pediatric CSCI patients. MI evoked NP in some of the pediatric CSCI patients. Compared with patients who did not experience NP, patients who experienced NP during MI showed larger GMV in the right primary sensorimotor cortex (PSMC) and insula. When using the GMV of the right PSMC and insula in combination as a predictor, the area under the curve (AUC) reached 0.824. Our study demonstrated that MI could evoke NP in some pediatric CSCI patients, but not in others. The individual differences in brain reorganization of the right PSMC and insula may contribute to the different effects of MI on NP. Moreover, the GMV of the right PSMC and insula in combination may be an effective indicator for screening pediatric CSCI patients before MI training therapy.

The relationship between triglyceride-glucose index and prospective key clinical outcomes in patients hospitalised for coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a dependable alternative for assessing insulin resistance (IR), given its simplicity, cost-effectiveness, and strong correlation with IR. The relationship between the TyG index and adverse outcomes in patients with coronary heart disease (CHD) is not well established. This study examines the association of the TyG index with long-term adverse outcomes in hospitalized CHD patients. METHODS: In this single-center prospective cohort study, 3321 patients hospitalized with CHD were included. Multivariate Cox regression models were employed to assess the associations between the TyG index and the incidence of all-cause mortality and major adverse cardiovascular events (MACEs). To examine potential nonlinear associations, restricted cubic splines and threshold analysis were utilized. RESULTS: During a follow-up period of 9.4 years, 759 patients (22.9%) succumbed to mortality, while 1291 (38.9%) experienced MACEs. Threshold analysis demonstrated a significant "U"-shaped nonlinear relationship with MACEs, with different hazard ratios observed below and above a TyG index of 8.62 (below: HR 0.71, 95% CI 0.50-0.99; above: HR 1.28, 95% CI 1.10-1.48). Notably, an increased risk of all-cause mortality was observed only when the TyG index exceeded 8.77 (HR 1.53, 95% CI 1.19-1.96). CONCLUSIONS: This study reveals a nonlinear association between the TyG index and both all-cause mortality and MACEs in hospitalized CHD patients with CHD. Assessing the TyG index, particularly focusing on individuals with extremely low or high TyG index values, may enhance risk stratification for adverse outcomes in this patient population.

GLP-1 signaling-regulated SNAP25 is involved in improved insulin secretion in diabetic GK rats after Roux-en-Y gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved ß-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of ß-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND RESULTS: RYGB or sham surgery was conducted in GK rats. mRNA and protein expression of SNAP25 was assessed by qPCR and Western blot, respectively. Occupancy of CREB and acetyltransferase CBP and acetylation of histone H3 (ACH3) at the Snap25 promoter were determined using ChIP assay. RYGB led to increased SNAP25 expression and CREB phosphorylation in islets from GK rats. Increased SNAP25 improved GSIS in ß-cells cultured in high glucose conditions. Consistent with increased plasma GLP-1 after RYGB, GLP-1R agonist exendin4 increased SNAP25 expression and CREB phosphorylation in ß-cells. Mechanistically, exendin4 promoted the recruitment of CREB and CBP, thereby increasing ACH3 at the Snap25 promoter. Consistently, inhibition of CBP attenuated the effect of exendin4 on SNAP25 expression. Furthermore, the knockdown of SNAP25 diminished the increase of GSIS potentiated by chronic GLP-1 culture in INS-1 832/13 cells. CONCLUSIONS: Our findings unravel the novel mechanisms of RYGB-enhanced SNAP25 expression in ß-cells, and SNAP25 may contribute to the improved ß-cell secretory function induced by RYGB.