Exploring the anti-ischemic stroke potential of wogonoside: Insights from Nrf2/Sirt3 signaling pathway and UPLC-TripleTOF-MS/MS-based metabolomics.

Ischemic stroke, accounting for 80 % of all strokes, is a major cause of morbidity and mortality worldwide. However, effective and safe pharmacotherapy options for ischemic injury are limited. This study investigated the therapeutic effects of wogonoside, a compound derived from Radix Scutellariae, on ischemia/reperfusion (I/R) injury. The results showed that wogonoside treatment had significant therapeutic effects in rats with middle cerebral artery occlusion. It effectively reduced mortality rates, neurological deficits, cerebral infarct size, and brain water content. In an in vitro model using PC12 cells, wogonoside activated the Nrf2/Sirt3 signaling pathway. This activation contributed to the attenuation of oxidative damage and inflammation. Metabolomics analysis revealed increased levels of γ-aminobutyric acid (GABA) and glutathione in response to wogonoside treatment, suggesting their potential as therapeutic biomarkers for ischemic stroke. Additionally, wogonoside restored perturbed energy metabolism, including the tricarboxylic acid cycle. Wogonoside has the potential to ameliorate cerebral ischemic injury by targeting GABA-related amino acid metabolism, energy metabolism, and glutathione metabolism, maintaining redox homeostasis, and attenuating oxidative stress. These findings provide valuable insights into the protective mechanisms of wogonoside in cerebral I/R injury and highlight the promising therapeutic approach of wogonoside in the treatment of ischemic stroke.

Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis.

Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins. Methods: We conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS. The plasma proteins were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) database, encompassing GWAS data for 2,940 plasma proteins. Additionally, GWAS data for AS were extracted from the R9 version of the Finnish database, including 2,860 patients and 270,964 controls. The colocalization analysis was executed to identify shared causal variants between plasma proteins and AS. Finally, we examined the potential adverse effects of druggable proteins for AS therapy by conducting a phenome-wide association study (PheWAS) utilizing the extensive Finnish database in version R9, encompassing 2,272 phenotypes categorized into 46 groups. Results: The findings revealed a positive genetic association between the predicted plasma levels of six proteins and an elevated risk of AS, while two proteins exhibited an inverse association with AS risk (P fdr < 0.05). Among these eight plasma proteins, colocalization analysis identified AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13 as shared variation with AS(PPH3+PPH4>0.8), suggesting that they represent potential direct targets for AS intervention. Further phenotype-wide association studies have shown some potential side effects of these six targets (P fdr < 0.05). Conclusion: Our investigation examined the causal connections between six plasma proteins and AS, providing a comprehensive understanding of potential therapeutic targets.

Identification of hub genes involved in GA-regulated coleoptile elongation under submerged germinations in rice.

Submergence stress hinders the direct seeding in rice cultivation. Rapid elongation of rice seed coleoptiles to reach the water surface enables rice to survive submergence stress. Gibberellin (GA) positively influences rice growth. However, the molecular mechanisms underlying GA-regulated coleoptile elongation under submergence conditions remain unclear. Here, we performed a WGCNA analysis to preliminarily investigate the mechanisms. Our results identify four key modules with a high correlation to the GA regulation of rice submergence tolerance. The genes within these modules are mainly involved in Golgi apparatus and carbohydrate metabolic pathways, suggesting involvement of these biological processes in enhancing rice submergence tolerance. Moreover, natural variation analysis reveals that the hub genes, specifically, Os03g0337900, Os03g0355600, and Os07g0638400, exhibited a strong correlation with the subspecies divergence of the coleoptile elongation phenotype. Mutation of Os07g0638400 results in a lower germination potential and a stronger inhibition of coleoptile elongation under submergence conditions in rice, indicating the reliability of the analyses. The hub genes identified in this study provide deep insights into understanding the molecular mechanisms underlying GA-dependent submergence stress tolerance in rice and provide a theoretical basis for innovating rice germplasm for direct seeding application.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Acceptor Copolymerized Axially Chiral Conjugated Polymers with TADF Properties for Efficient Circularly Polarized Electroluminescence.

Chiral conjugated polymer has promoted the development of the efficient circularly polarized electroluminescence (CPEL) device, nevertheless, it remains a challenge to develop chiral polymers with high electroluminescence performance. Herein, by the acceptor copolymerization of axially chiral biphenyl emitting skeleton and benzophenone, a pair of axially chiral conjugated polymers namely R-PAC and S-PAC are synthesized. The target polymers exhibit obvious thermally activated delayed fluorescence (TADF) activities with high photoluminescence quantum yields of 81%. Moreover, the chiral polymers display significant circularly polarized luminescence features, with luminescence dissymmetry factor (|glum|) of nearly 3 × 10-3. By using the chiral polymers as emitters, the corresponding circularly polarized organic light-emitting diodes (CP-OLEDs) exhibit efficient CPEL signals with electroluminescence dissymmetry factor |gEL| of 3.4 × 10-3 and high maximum external quantum efficiency (EQEmax) of 17.8%. Notably, considering both EQEmax and |gEL| comprehensively, the device performance of R-PAC and S-PAC is the best among all the reported CP-OLEDs with chiral conjugated polymers as emitters. This work provides a facile approach to constructing chiral conjugated TADF polymers and discloses the potential of axially chiral conjugated luminescent skeletons in architecting high-performance CP-OLEDs.

B,N-Embedded Hetero[9]helicene Toward Highly Efficient Circularly Polarized Electroluminescence.

The intrinsic helical π-conjugated skeleton makes helicenes highly promising for circularly polarized electroluminescence (CPEL). Generally, carbon helicenes undergo low external quantum efficiency (EQE), while the incorporation of a multi-resonance thermally activated delayed fluorescence (MR-TADF) BN structure has led to an improvement. However, the reported B,N-embedded helicenes all show low electroluminescence dissymmetry factors (gEL), typically around 1×10-3. Therefore, the development of B,N-embedded helicenes with both a high EQE and gEL value is crucial for achieving highly efficient CPEL. Herein, a facile approach to synthesize B,N-embedded hetero[9]helicenes, BN[9]H, is presented. BN[9]H shows a bright photoluminescence with a maximum at 578 nm with a high luminescence dissymmetry factor (|glum|) up to 5.8×10-3, attributed to its inherited MR-TADF property and intrinsic helical skeleton. Furthermore, circularly polarized OLED devices incorporating BN[9]H as an emitter show a maximum EQE of 35.5 %, a small full width at half-maximum of 48 nm, and, more importantly, a high |gEL| value of 6.2×10-3. The Q-factor (|EQE×gEL|) of CP-OLEDs is determined to be 2.2×10-3, which is the highest among helicene analogues. This work provides a new approach for the synthesis of higher helicenes and paves a new way for the construction of highly efficient CPEL materials.

Anion-Reinforced Solvating Ionic Liquid Electrolytes Enabling Stable High-Nickel Cathode in Lithium-Metal Batteries.

Ionic liquid electrolytes (ILEs) are promising to develop high-safety and high-energy-density lithium-metal batteries (LMBs). Unfortunately, ILEs normally face the challenge of sluggish Li+ transport due to increased ions' clustering caused by Coulombic interactions. Here a type of anion-reinforced solvating ILEs (ASILEs) is discovered, which reduce ions' clustering by enhancing the anion-cation coordination and promoting more anions to enter the internal solvation sheath of Li+ to address this concern. The designed ASILEs, incorporating chlorinated hydrocarbons and two anions, bis(fluorosulfonyl) imide (FSI- ) and bis(trifluoromethanesulfonyl) imide (TFSI- ), aim to enhance Li+ transport ability, stabilize the interface of the high-nickel cathode material (LiNi0.8 Co0.1 Mn0.1 O2 , NCM811), and retain fire-retardant properties. With these ASILEs, the Li/NCM811 cell exhibits high initial specific capacity (203 mAh g-1 at 0.1 C), outstanding capacity retention (81.6% over 500 cycles at 1.0 C), and excellent average Coulombic efficiency (99.9% over 500 cycles at 1.0 C). Furthermore, an Ah-level Li/NCM811 pouch cell achieves a notable energy density of 386 Wh kg-1 , indicating the practical feasibility of this electrolyte. This research offers a practical solution and fundamental guidance for the rational design of advanced ILEs, enabling the development of high-safety and high-energy-density LMBs.

CT­based radiomics analysis of consolidation characteristics in differentiating pulmonary disease of non­tuberculous mycobacterium from pulmonary tuberculosis.

Global incidence rate of non-tuberculous mycobacteria (NTM) pulmonary disease has been increasing rapidly. In some countries and regions, its incidence rate is higher than that of tuberculosis. It is easily confused with tuberculosis. The topic of this study is to identify two diseases using CT radioomics. The aim in the present study was to investigate the value of CT-based radiomics to analyze consolidation features in differentiation of non-tuberculous mycobacteria (NTM) from pulmonary tuberculosis (TB). A total of 156 patients (75 with NTM pulmonary disease and 81 with TB) exhibiting consolidation characteristics in Shandong Public Health Clinical Center were retrospectively analyzed. Subsequently, 305 regions of interest of CT consolidation were outlined. Using a random number generated via a computer, 70 and 30% of consolidations were allocated to the training and the validation cohort, respectively. By means of variance threshold, when investigating the effective radiomics features, SelectKBest and the least absolute shrinkage and selection operator regression method were employed for feature selection and combined to calculate the radiomics score. K-nearest neighbor (KNN), support vector machine (SVM) and logistic regression (LR) were used to analyze effective radiomics features. A total of 18 patients with NTM pulmonary disease and 18 with TB possessing consolidation characteristics in Jinan Infectious Disease Hospital were collected for external validation of the model. A total of three methods was used in the selection of 52 optimal features. For KNN, the area under the curve (AUC; sensitivity, specificity) for the training and validation cohorts were 0.98 (0.93, 0.94) and 0.90 (0.88, 083), respectively; for SVM, AUC was 0.99 (0.96, 0.96) and 0.92 (0.86, 0.85) and for LR, AUC was 0.99 (0.97, 0.97) and 0.89 (0.88, 0.85). In the external validation cohort, AUC values of models were all >0.84 and LR classifier exhibited the most significant precision, recall and F1 score (0.87, 0.94 and 0.88, respectively). LR classifier possessed the best performance in differentiating diseases. Therefore, CT-based radiomics analysis of consolidation features may distinguish NTM pulmonary disease from TB.

Carbon Dots with Antioxidant Capacity for Detecting Glucose by Fluorescence and Repairing High-Glucose Damaged Glial Cells.

Diabetic mellitus management extends beyond blood glucose monitoring to the essential task of mitigating the overexpression of reactive oxygen species (ROS), particularly vital for cellular repair, especially within the nervous system. Herein, antioxidant carbon dots (Arg-CDs) were designed and prepared using anhydrous citric acid, L-arginine, and ethylenediamine as sources through a hydrothermal method. Arg-CDs exhibited excellent scavenging ability to 2,2-Diphenyl-1-picrylhydrazyl (DPPH∙), and fluorescence response to hydroxyl radicals (∙OH), a characteristic representative of reactive oxygen species (ROS). Assisted by glucose oxidase and Fe2+, Arg-CDs showed a sensitive and selective response to glucose. The quenching mechanism of Arg-CDs by formed ∙OH was based on the static quenching effect (SQE). The analytical performance of this method for glucose detection encompassed a wide linear range (0.3-15 µM), a low practical limit of detection (0.1 µM) and practical applicability for blood glucose monitoring. In an in vitro model employing glial cells (BV2 cells), it was observed that high glucose medium led to notable cellular damage ascribed to the excessive ROS production from hyperglycemia. The diminished and apoptotic glial cells were gradually recovered by adding increased contents of Arg-CDs. This work illustrates a promising area that designs effective carbon dots with antioxidant capacity for the dual applications of detection and cell repairing based on the utilization of antioxidant activity.

How Information Framing Nudges Acceptance of China's Delayed Retirement Policy: A Moderated Mediation Model of Anchoring Effects and Perceived Fairness.

China's delayed retirement policy will be prudently rolled out at the appropriate time, yet the public's acceptance of this policy is concerning. To address this issue, our endeavor explores the impact of framing and anchoring effects on policy acceptance, aiming to mitigate the populace's resistance to the new policy. We conducted two survey studies on the Chinese population aged 16-65. Achieved through an online survey, Study 1 (N = 225) demonstrated that information framing significantly influences the public's acceptance of the delayed retirement policy. It was found that perceived fairness plays a mediating role between information framing and policy acceptance. Notably, the positive frame had a more pronounced effect on acceptance than its negative counterpart, with the positive presentation being perceived as more fair. Study 2 (N = 383), utilizing a combination of online and offline approaches, revealed that the anchoring effect moderates the relationship between information framing and perceived fairness. The interaction of anchoring and framing effects significantly influences perceived fairness, subsequently promoting public policy acceptance. The interplay between anchoring and framing effects significantly shapes perceived fairness, in turn bolstering the public's receptiveness to policy. These insights offer reasonable communication strategies for the smooth advancement of new policies, further enriching the field of behavioral science.

B-N Covalent Bond Embedded Double Hetero-[n]helicenes for Pure Red Narrowband Circularly Polarized Electroluminescence with High Efficiency and Stability.

Chiral B/N embedded multi-resonance (MR) emitters open a new paradigm of circularly polarized (CP) organic light-emitting diodes (OLEDs) owing to their unique narrowband spectra. However, pure-red CP-MR emitters and devices remain exclusive in literature. Herein, by introducing a B-N covalent bond to lower the electron-withdrawing ability of the para-positioned B-π-B motif, the first pair of pure-red double hetero-[n]helicenes (n = 6 and 7) CP-MR emitter peaking 617 nm with a small full-width at half-maximum of 38 nm and a high photoluminescence quantum yield of ≈100% in toluene is developed. The intense mirror-image CP light produced by the enantiomers is characterized by high photoluminescence dissymmetry factors (gPL ) of +1.40/-1.41 × 10-3 from their stable helicenes configuration. The corresponding devices using these enantiomers afford impressive CP electroluminescence dissymmetry factors (gEL ) of +1.91/-1.77 × 10-3 , maximum external quantum efficiencies of 36.6%/34.4% and Commission Internationale de I'Éclairage coordinates of (0.67, 0.33), exactly satisfying the red-color requirement specified by National Television Standards Committee (NTSC) standard. Notably a remarkable long LT95 (operational time to 95% of the initial luminance) of ≈400 h at an initial brightness of 10,000 cd m-2 is also observed for the same device, representing the most stable CP-OLED up to date.

Study on the acute toxicity of trichlorfon and its breakdown product dichlorvos to goldfish (Carassius auratus) based on 1H NMR metabonomics.

Trichlorfon, one of the most widely used organophosphate insecticides, is commonly employed in aquaculture and agriculture to combat parasitic infestations. However, its inherent instability leads to rapid decomposition into dichlorvos (DDVP), increasing its toxicity by eightfold. Therefore, the environmental effects of trichlorfon in real-world scenarios involve the combined effects of trichlorfon and its degradation product, DDVP. In this study, we systematically investigated the degradation of trichlorfon in tap water over time using HPLC and LC-MS/MS analysis. Subsequently, an experiment was conducted to assess the acute toxicity of trichlorfon and DDVP on goldfish (Carassius auratus), employing a 1H NMR-based metabolic approach in conjunction with serum biochemistry, histopathological inspection, and correlation network analysis. Exposure to trichlorfon and its degradation product DDVP leads to increased lipid peroxidation, reduced antioxidant activity, and severe hepatotoxicity and nephrotoxicity in goldfish. Based on the observed pathological changes and metabolite alterations, short-term exposure to trichlorfon significantly affected the liver and kidney functions of goldfish, while exerting minimal influence on the brain, potentially due to the presence of the blood-brain barrier. The changes in the metabolic profile indicated that trichlorfon and DDVP influenced several pathways, including oxidative stress, protein synthesis, energy metabolism, and nucleic acid metabolism. This study demonstrated the applicability and potential of 1H NMR-based metabonomics in pesticide environmental risk assessment, providing a feasible method for the comprehensive study of pesticide toxicity in water environments.

Torachrysone-8-O-ß-d-glucoside mediates anti-inflammatory effects by blocking aldose reductase-catalyzed metabolism of lipid peroxidation products.

Aldose reductase (AR) is an important enzyme involved in the reduction of various aldehyde and carbonyl compounds, including the highly reactive and toxic 4-hydroxynonenal (4-HNE), which has been linked to the progression of various pathologies such as atherosclerosis, hyperglycemia, inflammation, and tumors. AR inhibitors have potential therapeutic benefits for these diseases by reducing lipid peroxidation and mitigating the harmful effects of reactive aldehydes. In this study, we found that torachrysone-8-O-ß-d-glucoside (TG), a natural product isolated from Polygonum multiflorum Thunb., functions as an effective inhibitor of AR, exhibiting potent effects in clearing reactive aldehydes and reducing inflammation. TG up-regulated the mRNA levels of several antioxidant factors downstream of NRF2, especially glutathione S-transferase (GST), which is significantly increased, thus detoxifying 4-HNE by facilitating the conjugation of 4-HNE to glutathione, forming glutathione-4-hydroxynonenal (GS-HNE). By employing a combination of molecular docking, cellular thermal shift assay, and enzyme activity experiments, we demonstrated that TG exhibited strong binding affinity with AR and inhibited its activity and blocked the conversion of GS-HNE to glutathionyl-1,4-dihydroxynonene (GS-DHN), thereby preventing the formation of protein adducts and inducing severe cellular damage. This study provides novel insights into the anti-inflammatory mechanisms of AR inhibitors and offers potential avenues for developing therapeutic strategies for AR-related pathologies. Our findings suggest that TG, as an AR inhibitor, may hold promise as a therapeutic agent for treating conditions characterized by excessive lipid peroxidation and inflammation. Further investigations are needed to fully explore the clinical potential of TG and evaluate its efficacy in the treatment and management of these complex diseases.

Visualization of Thromboinflammation by 18F-DPA-714 PET in a Stroke Patient.

ABSTRACT: A 44-year-old man who presented with progressive right limb weakness was diagnosed with ischemic stroke. He was referred for 18F-DPA-714 PET/CT for evaluation of the disease. 18F-DPA-714 PET/CT showed increased uptake of the intracranial thrombus. This DPA-714-avid thrombus highly suggested the involvement of immune cells in the extension of the clot resulting in neurological deterioration. This present case suggested that 18F-DPA-714 PET might be a promising tracer in visualizing thromboinflammation in vivo.

Preeclampsia promotes autism in offspring via maternal inflammation and fetal NFκB signaling.

Preeclampsia (PE) is a risk factor for autism spectrum disorder (ASD) in offspring. However, the exact mechanisms underlying the impact of PE on progeny ASD are not fully understood, which hinders the development of effective therapeutic approaches. This study shows the offspring born to a PE mouse model treated by Nω-nitro-L-arginine methyl ester (L-NAME) exhibit ASD-like phenotypes, including neurodevelopment deficiency and behavioral abnormalities. Transcriptomic analysis of the embryonic cortex and adult offspring hippocampus suggested the expression of ASD-related genes was dramatically changed. Furthermore, the level of inflammatory cytokines TNFα in maternal serum and nuclear factor kappa B (NFκB) signaling in the fetal cortex were elevated. Importantly, TNFα neutralization during pregnancy enabled to ameliorate ASD-like phenotypes and restore the NFκB activation level in the offspring exposed to PE. Furthermore, TNFα/NFκB signaling axis, but not L-NAME, caused deficits in neuroprogenitor cell proliferation and synaptic development. These experiments demonstrate that offspring exposed to PE phenocopies ASD signatures reported in humans and indicate therapeutic targeting of TNFα decreases the likelihood of bearing children with ASD phenotypes from PE mothers.

Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.

Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.

Collateral circulation status-guided mechanical thrombectomy in pediatric stroke with an extended ghost infarct core: illustrative case.

BACKGROUND: Mechanical thrombectomy (MT) has been proved to be a highly effective therapy to treat acute ischemic stroke due to large vessel occlusion. Often, the ischemic core extent on baseline imaging is an important determinant for endovascular treatment eligibility. However, computed tomography (CT) perfusion (CTP) or diffusion-weighted imaging may overestimate the infarct core on admission and, consequently, smaller infarct lesions called "ghost infarct cores." OBSERVATIONS: A 4-year-old, previously healthy boy presented with acute-onset, right-sided weakness and aphasia. Fourteen hours after the onset of symptoms, the patient presented with a National Institutes of Health Stroke Scale (NIHSS) score of 22, and magnetic resonance angiography demonstrated a left middle cerebral artery occlusion. MT was not considered because of a large infarct core (infarct core volume: 52 mL; mismatch ratio 1.6 on CTP). However, multiphase CT angiography indicated good collateral circulation, which encouraged MT. Complete recanalization was achieved via MT at 16 hours after the onset of symptoms. The child's hemiparesis improved. Follow-up magnetic resonance imaging was nearly normal and showed that the baseline infarct lesion was reversible, in agreement with neurological improvement (NIHSS score 1). LESSONS: The selection of pediatric stroke with a delayed time window guided by good collateral circulation at baseline seems safe and efficacious, which suggests a promising value of vascular window.

A real-time automated bone age assessment system based on the RUS-CHN method.

Background: Bone age is the age of skeletal development and is a direct indicator of physical growth and development in children. Most bone age assessment (BAA) systems use direct regression with the entire hand bone map or first segmenting the region of interest (ROI) using the clinical a priori method and then deriving the bone age based on the characteristics of the ROI, which takes more time and requires more computation. Materials and methods: Key bone grades and locations were determined using three real-time target detection models and Key Bone Search (KBS) post-processing using the RUS-CHN approach, and then the age of the bones was predicted using a Lightgbm regression model. Intersection over Union (IOU) was used to evaluate the precision of the key bone locations, while the mean absolute error (MAE), the root mean square error (RMSE), and the root mean squared percentage error (RMSPE) were used to evaluate the discrepancy between predicted and true bone age. The model was finally transformed into an Open Neural Network Exchange (ONNX) model and tested for inference speed on the GPU (RTX 3060). Results: The three real-time models achieved good results with an average (IOU) of no less than 0.9 in all key bones. The most accurate outcomes for the inference results utilizing KBS were a MAE of 0.35 years, a RMSE of 0.46 years, and a RMSPE of 0.11. Using the GPU RTX3060 for inference, the critical bone level and position inference time was 26 ms. The bone age inference time was 2 ms. Conclusions: We developed an automated end-to-end BAA system that is based on real-time target detection, obtaining key bone developmental grade and location in a single pass with the aid of KBS, and using Lightgbm to obtain bone age, capable of outputting results in real-time with good accuracy and stability, and able to be used without hand-shaped segmentation. The BAA system automatically implements the entire process of the RUS-CHN method and outputs information on the location and developmental grade of the 13 key bones of the RUS-CHN method along with the bone age to assist the physician in making judgments, making full use of clinical a priori knowledge.

Clinical characteristics and survival analysis of class I pulmonary arterial hypertension.

PURPOSE: To analyze the clinical data and prognosis of patients with World Health Organization (WHO) functional class I pulmonary arterial hypertension (PAH). METHODS: This research retrospectively analyzed the clinical data (baseline, laboratory as well as echocardiography and right heart catheterization data) of 63 class I PAH patients diagnosed and treated in the Department of Cardiology, First Affiliated Hospital of Zhengzhou University, between January 2021 and June 2022. The mean follow-up time was 10.7±6.5 months. The treatment and prognosis of the patients were analyzed. RESULTS: Among the class I PAH patients, the average age at diagnosis was 39.7±12.7 years, with females accounting for 92.1%; 44.4% of patients were at grade III or IV; 55.6% were at medium-high risk. In the subgroup analysis, there were more cases with grade III/IV cardiac function (P=0.03) and high risk in idiopathic PAH (IPAH) group than those in congenital heart disease-associated (CHD-PAH) and connective tissue disease-associated PAH (CTD-PAH) groups (P=0.04). CHD-PAH patients tended to present with higher pulmonary systolic blood pressure, mean pulmonary artery pressure and pulmonary vascular resistance than CTD-PAH patients (P<0.01), while IPAH patients had worse right ventricular end-systolic and end-diastolic volumes (P<0.05). The three subgroups showed no obvious differences in echocardiographic indexes (right atrial size, right ventricular size and pulmonary artery systolic pressure) and related laboratory indexes (blood routines and hepatorenal function). In terms of the targeted drug therapy for PAH, the proportion of dual-drug combination therapy was the highest (48.1%), followed by monotherapy (35%) and triple combination therapy (15.9%). Nearly half (48.7%) of CTD-PAH cases were first diagnosed in the Rheumatology and Immunology Department, and all of them were given targeted drug therapy for PAH. After a mean follow-up of 10.7±6.5 months, a total of 8 endpoint events occurred, including 3 deaths due to CTD-PAH complicated with serious complications of other organs. The 1-year survival rate for all the included PAH patients was 95.2%. CONCLUSIONS: In the era of targeted therapy, class I PAH patients in China have a high early survival rate, a high proportion of combined therapy and strong multidisciplinary attention.