Decoding Wilson disease: a machine learning approach to predict neurological symptoms.

Objectives: Wilson disease (WD) is a rare autosomal recessive disorder caused by a mutation in the ATP7B gene. Neurological symptoms are one of the most common symptoms of WD. This study aims to construct a model that can predict the occurrence of neurological symptoms by combining clinical multidimensional indicators with machine learning methods. Methods: The study population consisted of WD patients who received treatment at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from July 2021 to September 2023 and had a Leipzig score ≥ 4 points. Indicators such as general clinical information, imaging, blood and urine tests, and clinical scale measurements were collected from patients, and machine learning methods were employed to construct a prediction model for neurological symptoms. Additionally, the SHAP method was utilized to analyze clinical information to determine which indicators are associated with neurological symptoms. Results: In this study, 185 patients with WD (of whom 163 had neurological symptoms) were analyzed. It was found that using the eXtreme Gradient Boosting (XGB) to predict achieved good performance, with an MCC value of 0.556, ACC value of 0.929, AUROC value of 0.835, and AUPRC value of 0.975. Brainstem damage, blood creatinine (Cr), age, indirect bilirubin (IBIL), and ceruloplasmin (CP) were the top five important predictors. Meanwhile, the presence of brainstem damage and the higher the values of Cr, Age, and IBIL, the more likely neurological symptoms were to occur, while the lower the CP value, the more likely neurological symptoms were to occur. Conclusions: To sum up, the prediction model constructed using machine learning methods to predict WD cirrhosis has high accuracy. The most important indicators in the prediction model were brainstem damage, Cr, age, IBIL, and CP. It provides assistance for clinical decision-making.

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures.

Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.

FoxO1 silencing in Atp7b-/- neural stem cells attenuates high copper-induced apoptosis via regulation of autophagy.

Wilson disease (WD) is a severely autosomal genetic disorder triggered by dysregulated copper metabolism. Autophagy and apoptosis share common modulators that process cellular death. Emerging evidences suggest that Forkhead Box O1 over-expression (FoxO1-OE) aggravates abnormal autophagy and apoptosis to induce neuronal injury. However, the underlying mechanisms remain undetermined. Herein, the aim of this study was to investigate how regulating FoxO1 affects cellular autophagy and apoptosis to attenuate neuronal injury in a well-established WD cell model, the high concentration copper sulfate (CuSO4, HC)-triggered Atp7b-/- (Knockout, KO) neural stem cell (NSC) lines. The FoxO1-OE plasmid, or siRNA-FoxO1 (siFoxO1) plasmid, or empty vector plasmid was stably transfected with recombinant lentiviral vectors into HC-induced Atp7b-/- NSCs. Toxic effects of excess deposited copper on wild-type (WT), Atp7b-/- WD mouse hippocampal NSCs were tested by Cell Counting Kit-8 (CCK-8). Subsequently, the FoxO1 expression was evaluated by immunofluorescence (IF) assay, western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Meanwhile, the cell autophagy and apoptosis were evaluated by flow cytometry (FC), TUNEL staining, 2,7-dichlorofluorescein diacetate (DCFH-DA), JC-1, WB, and qRT-PCR. The current study demonstrated a strong rise in FoxO1 levels in HC-treated Atp7b-/- NSCs, accompanied with dysregulated autophagy and hyperactive apoptosis. Also, it was observed that cell viability was significantly decreased with the over-expressed FoxO1 in HC-treated Atp7b-/- WD model. As intended, silencing FoxO1 effectively inhibited abnormal autophagy in HC-treated Atp7b-/- NSCs, as depicted by a decline in LC3II/I, Beclin-1, ATG3, ATG7, ATG13, and ATG16, whereas simultaneously increasing P62. In addition, silencing FoxO1 suppressed apoptosis via diminishing oxidative stress (OS), and mitochondrial dysfunction in HC-induced Atp7b-/- NSCs. Collectively, these results clearly demonstrate the silencing FoxO1 has the neuroprotective role of suppressing aberrant cellular autophagy and apoptosis, which efficiently attenuates neuronal injury in WD.

Abnormalities in subcortical function and their treatment response in Wilson's disease.

Extensive neuroimaging abnormalities in subcortical regions build the pathophysiological basis of Wilson's disease (WD). Yet, subcortical topographic organization fails to articulate, leaving a huge gap in understanding the neural mechanism of WD. Thus, how functional abnormalities of WD subcortical regions influence complex clinical symptoms and response to treatment remain unknown. Using resting-state functional MRI data from 232 participants (including 130 WD patients and 102 healthy controls), we applied a connectivity-based parcellation technique to develop a subcortical atlas for WD. The atlas was further used to investigate abnormalities in subcortical function (ASF) by exploring intrasubcortical functional connectivity (FC) and topographic organization of cortico-subcortical FC. We further used support vector machine (SVM) to integrate these functional abnormalities into the ASF score, which serves as a biomarker for characterizing individual subcortical dysfunction for WD. Finally, the baseline ASF score and one-year treatment data of the follow-up WD patients were used to assess treatment response. A group set of subcortical parcellations was evaluated, in which 26 bilateral regions well recapitulated the anatomical nuclei of the subcortical areas of WD. The results of cortico-subcortical FC and intrasubcortical FC reveal that dysfunction of the somatomotor networks-lenticular nucleus-thalamic pathways is involved in complex symptoms of WD. The ASF score was able to characterize disease progression and was significantly associated with treatment response of WD. Our findings provide a comprehensive elaboration of functional abnormalities of WD subcortical regions and reveal their association with clinical presentations, improving our understanding of the functional neural underpinnings in WD. Furthermore, abnormalities in subcortical function could serve as a potential biomarker for understanding the disease progression and evaluating treatment response of WD.

Investigation on the interaction of NH3&CH4 co-activated char under reburning conditions.

In the current global context, there is a pressing need to curtail greenhouse gas emissions, making the utilization of a coal and zero-carbon energy blend an imperative strategy for reducing carbon emissions from coal-fired power generation. The planar flame burner serves as a tool to simulate the temperature and atmospheric conditions within the reburning zone, facilitating extensive examination of the physical and chemical structural alterations, as well as the nitrogen oxide reduction potential, during NH3/CH4 activation for reburning pulverized coal. Experimental results underscore that blending high-activity fuels optimizes the combustion performance of coal char. Through the addition of NH3 and CH4, the NO reduction capability of coal char is bolstered by approximately 0.67 times compared to sole reliance on recirculating flue gas transport. Furthermore, NH3 introduction facilitates the conversion of C]O double bonds into C-O single bonds, rendering them more amenable to reduction by NO. While the joint influence of NH3 and CH4 does not significantly impact char particle size, it does foster the evolution of N-Q to N-5 and N-6 on the char surface. Furthermore, there was a significant increase in the BET-specific surface area, which rose by 50%. Additionally, the total pore volume increased by approximately 21.43%. The comprehensive understanding of NH3 and CH4 modified pulverized coal reburning technology holds significant promise for optimizing power plant operations and mitigating carbon dioxide and nitrogen oxide emissions.

Analysis of risk factors for fatty liver disease in children with Wilson's disease.

BACKGROUND AND AIMS: Many children with Wilson's disease are complicated with dyslipidemia. The aim of this study was to investigate the risk factors for the development of fatty liver disease (FLD) in children with Wilson's disease. METHODS: We evaluated sex, age, weight, the disease course, treatment course, clinical classification, alanine transaminase (ALT), aspartate transaminase, γ-glutamyl transpeptidase, total biliary acid, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, uric acid, fibrinogen (FBG), creatinine, procollagen III N-terminal propeptide, laminin, hyaluronic acid, type IV collagen, and performed receiver operating characteristic curve analysis to investigate the forecast value of individual biochemical predictors and combined predictive indicators to evaluate FLD in Wilson's disease. RESULTS: The multivariate logistic regression analysis revealed that ALT [odds ratio (OR), 1.011; 95% confidence interval (CI), 1.004-1.02; P  = 0.006], uric acid (OR, 1.01; 95% CI, 1.002-1.018; P  = 0.017), FBG (OR, 3.668; 95% CI, 1.145-13.71; P  = 0.037), creatinine (OR, 0.872; 95% CI, 0.81-0.925; P  < 0.001), and laminin (OR, 1.01; 95% CI, 1.002-1.018; P  = 0.017) acted as independent risk factors in Wilson's disease complicated with FLD. The receiver operating characteristic curves for combined predictive indicators demonstrated an area under the curve values of 0.872, which was found to be a significant predictors for FLD in Wilson's disease. CONCLUSIONS: We screened out the most important risk factors, namely ALT, uric acid, creatinine, FBG, and laminin for Wilson's disease complicated with FLD. The joint prediction achieved is crucial for identifying children with Wilson's disease complicated with FLD.

Characterization of renal damage in Wilson's disease-Detailed analysis of 20 Chinese cases.

OBJECTIVE: Copper metabolism disorder disease is thought to contribute to renal symptoms in Wilson's disease (WD). Nonetheless, there remains limited knowledge regarding the precise characteristics of renal damage in individuals with Wilson's disease, encompassing clinical presentations, biochemical indicators, imaging findings, and renal histopathological alterations. METHODS: In this study, 20 patients diagnosed with Wilson's disease and renal involvement were enrolled in our hospital. These patients met the validated European criteria for Wilson's disease, and those with primary kidney disease or secondary renal damage caused by other underlying conditions were excluded. The baseline data of patients were collected. Various biochemical and hematological parameters were monitored. Biochemical examinations were measured using an automatic biochemistry analyzer, blood routines were tested by flow cytometry analysis, 24-h urine copper was tested by atomic absorption spectrophotometer. Besides, CER was measured by turbidimetric immunoassay with a Hitachi 7020 automatic biochemical analyzer (the intraplate and interplate coefficients of variation were 2.7% and 5.13% respectively). Copper oxidase was tested by colorimetric method using p-phenylenediamine hydrochloride (the intraplate and interplate coefficients of variation were both <10%). Diagnostic criteria for Wilson's disease and kidney damage were established based on the European Association for the Study of the Liver (EASL) and CKD Epidemiology Collaboration guidelines, respectively. Statistical analysis was carried out using t-tests and χ2 tests in SPSS 22.0 software. Significant differences were considered when P<0.05. RESULTS: In those patients with Wilson's disease-related renal damage, edema, gross hematuria, oliguria, and lumbar pain were present in most patients. Microscopic haematuria and proteinuria were also observed in 19 patients. Compared to patients without renal involvement, those with renal complications exhibited a significant increase in white blood cell (WBC) and neutrophil counts (P<0.05). Additionally, patients with renal damage showed a noteworthy rise in both diastolic and systolic blood pressure, along with a significant reduction in hemoglobin levels (P<0.05). Color Doppler ultrasound results revealed diffuse lesions in both kidneys in 12 patients, renal cysts were identified in 5 patients, and 2 patients exhibited abnormal renal blood flow signals. Meanwhile, varying degrees of IgA, IgM, IgG-based immunoglobulins, complement C3 and C1q deposition in the glomerular mesangial area were detected by immunofluorescence. Furthermore, renal puncture biopsy results revealed a spectrum of findings, including minimal change nephrosis in 1 case, IgA nephropathy in 3 cases, atypical membranous proliferative nephropathy in 2 cases, and focal segmental glomerulosclerosis in 1 case. CONCLUSION: This study comprehensively elucidates the distinct attributes of renal damage related to Wilson's disease, while also speculating that renal dysfunction in Wilson's disease could be linked to immune complex deposition. Depending on the underlying pathogenesis, kidney injury associated with Wilson's disease can be classified as primary or secondary. To slow down the progression of renal impairment, it is essential to undergo a renal biopsy pathological examination as early as possible to clarify the type of impairment and take the appropriate treatment.

High-sensitivity and energy-efficient chloride ion sensors based on flexible printed carbon nanotube thin-film transistors for wearable electronics.

The advent of flexible single-walled carbon nanotube thin-film transistors (SWCNT-TFTs) has transformed electronics, providing significant benefits like low operating voltage, reduced power consumption, cost-effectiveness, and improved signal amplification. This study focuses on leveraging these attributes to develop a novel flexible high-sensitivity and energy-efficient chloride ion sensors based on printed flexible SWCNT-TFTs utilizing polymers-sorted semiconducting SWCNTs (sc-SWCNTs) as the active layers and ion liquids-poly(4-vinylphenol as dielectric layers along with the evaporated deposition of aluminum electrodes and printed silver electrodes as the gate and source-drain electrodes, respectively. The sensors exhibit several operational advantages, including low voltage requirements (≤1 V), rapid response speed (5.32 s), significant signal amplification (Up to 702.6 %), low power consumption (0.31 µJ at 1 mmol chloride ion), good repeatability, high sensitivity for both low and high concentrations of chloride ion (up to 100 mmol/L) and excellent mechanical flexibility (No obvious changes after bending for 10,000 times with a 5 mm radius). The detection mechanism of chloride ions was analyzed using X-ray Photoelectron Spectroscopy (XPS). It was found that chloride ions react with silver nanoparticles (AgNPs) to form silver chloride (AgCl) on printed electrodes, impeding carrier transport and reducing the currents in SWCNT TFTs. Importantly, our sensors' compatibility with smart devices allows for real-time monitoring of chloride ion levels in human sweat, offering significant potential for daily health monitoring.

1H-NMR-based metabolomics to dissect the traditional Chinese medicine promotes mesenchymal stem cell homing as intervention in liver fibrosis in mouse model of Wilson's disease.

BACKGROUND: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription. METHODS: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics. RESULTS: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-ß1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances. CONCLUSION: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.

Development and testing of a post competency scale for traditional Chinese medicine physicians undergoing standardized training.

Objective: To develop and test a post competency scale for traditional Chinese medicine (TCM) physicians undergoing standardized training to provide an applicable tool for scientific evaluation. Methods: Based on literature analysis, behavioral event interviews, and expert consultations, measurement questions were formulated and the initial scale was designed. A questionnaire survey was conducted from July 2022 to May 2023 among TCM physicians undergoing standardized training in China. The rationality of the scale was confirmed through item purification, factor analysis, and tests of reliability and validity. Results: The post competency scale consisted of three dimensions (TCM fundamentals and research abilities, TCM thinking and skill abilities, and personal traits and communication abilities) with 21 items. Exploratory factor analysis identified three common factors, accounting for a cumulative variance contribution rate of 62.165%. Confirmatory factor analysis demonstrated that the fit indices of the three-factor model fell within a relatively ideal level. The Cronbach's alpha coefficient of the scale was 0.885. Through convergent validity analysis, the standardized loading coefficients of the 21 items were >0.5, and the average extracted variance (AVE) of the three factors was also >0.5. Moreover, the square roots of the AVE values for each dimension exceeded the correlation coefficients between it and the other dimensions. Conclusions: The findings suggest that the post competency scale of TCM physicians undergoing standardized training can provide a reliable scientific basis for training and assessment within China.

Ammonia marine engine design for enhanced efficiency and reduced greenhouse gas emissions.

Pilot-diesel-ignition ammonia combustion engines have attracted widespread attentions from the maritime sector, but there are still bottleneck problems such as high unburned NH3 and N2O emissions as well as low thermal efficiency that need to be solved before further applications. In this study, a concept termed as in-cylinder reforming gas recirculation is initiated to simultaneously improve the thermal efficiency and reduce the unburned NH3, NOx, N2O and greenhouse gas emissions of pilot-diesel-ignition ammonia combustion engine. For this concept, one cylinder of the multi-cylinder engine operates rich of stoichiometric and the excess ammonia in the cylinder is partially decomposed into hydrogen, then the exhaust of this dedicated reforming cylinder is recirculated into the other cylinders and therefore the advantages of hydrogen-enriched combustion and exhaust gas recirculation can be combined. The results show that at 3% diesel energetic ratio and 1000 rpm, the engine can increase the indicated thermal efficiency by 15.8% and reduce the unburned NH3 by 89.3%, N2O by 91.2% compared to the base/traditional ammonia engine without the proposed method. At the same time, it is able to reduce carbon footprint by 97.0% and greenhouse gases by 94.0% compared to the traditional pure diesel mode.

Image-free single-pixel keypoint detection for privacy preserving human pose estimation.

Computer vision technology has been applied in various fields such as identification, surveillance, and robot vision. However, computer vision algorithms used for human-related tasks operate on human images, which raises data security and privacy concerns. In this Letter, we propose an image-free human keypoint detection technique using a few coded illuminations and a single-pixel detector. Our proposed method can complete the keypoint detection task at an ultralow sampling rate on a measured one-dimensional sequence without image reconstruction, thus protecting privacy from the data collection stage and preventing the acquisition of detailed visual information from the source. The network is designed to optimize both the illumination patterns and the human keypoint predictor with an encoder-decoder framework. For model training and validation, we used 2000 images from Leeds Sport Dataset and COCO Dataset. By incorporating EfficientNet backbone, the inference time is reduced from 4 s to 0.10 s. In the simulation, the proposed network achieves 91.7% average precision. Our experimental results show an average precision of 88.4% at a remarkably low sampling rate of 0.015. In summary, our proposed method has the advantages of privacy protection and resource efficiency, which can be applied to many monitoring and healthcare tasks, such as clinical monitoring, construction site monitoring, and home service robots.

Diagnostic and prognostic value of circulating tumor cells in renal cell cancer: A systematic review and meta-analysis.

Renal cell carcinoma (RCC) is a type of tumor with high morbidity and recurrence rates. The application of circulating tumor cells (CTCs) in RCC remains controversial. Hence, we performed a meta-analysis to elucidate the diagnostic and prognostic value of CTCs in RCC. To obtain a precise conclusion, a systematic search was conducted in Pubmed, Cochrane Database, Embase and Web of Science up to Dec 01, 2022. We also further identified the references in relevant studies. The diagnostic accuracy variables (sensitivity, specificity) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to access precise of CTCs and relationship between CTCs and disease stages, respectively. Heterogeneity test, sensitivity analysis, meta-regression and publishing bias were also applied. A total of 12 studies involving 767 patients were considered to be included in the final meta-analysis. The results revealed that the overall sensitivity, specificity of CTC detection in RCC were 45% (95%CI, 32-60%) and 99% (95%CI, 97-100%), respectively. In subgroup analysis, diagnostic sensitivity of CTCs in clear cell renal cell carcinoma (ccRCC) (69%, 95%CI; 50-88%) was significantly higher than other RCC subtypes (34%, 95%CI; 21-48%) (p<0.05). Meanwhile, advanced diseases (stage III-IV) were more likely to find CTCs than localized diseases (stage I-II) (OR, 2.29; 95%CI, 1.37-3.83; p = 0.002). This systematic review and meta-analysis demonstrated that CTC detection could be considered as a promising auxiliary diagnostic and staging method for RCC, especially ccRCC subtype. Meanwhile, the presence of cytokeratin-positive CTCs is highly likely associated with increased risk of poor prognosis in RCC.

High-Speed Centrifugation Efficiently Removes Immunogenic Elements in Osteochondral Allografts.

OBJECTIVES: The current clinical pulse lavage technique for flushing fresh osteochondral allografts (OCAs) to remove immunogenic elements from the subchondral bone is ineffective. This study aimed to identify the optimal method for removing immunogenic elements from OCAs. METHODS: We examined five methods for the physical removal of immunogenic elements from OCAs from the femoral condyle of porcine knees. We distributed the OCAs randomly into the following seven groups: (1) control, (2) saline, (3) ultrasound, (4) vortex vibration (VV), (5) low-pulse lavage (LPL), (6) high-pulse lavage (HPL), and (7) high-speed centrifugation (HSC). OCAs were evaluated using weight measurement, micro-computed tomography (micro-CT), macroscopic and histological evaluation, DNA quantification, and chondrocyte activity testing. Additionally, the subchondral bone was zoned to assess the bone marrow and nucleated cell contents. One-way ANOVA and paired two-tailed Student's t-test are used for statistical analysis. RESULTS: Histological evaluation and DNA quantification showed no significant reduction in marrow elements compared to the control group after the OCAs were treated with saline, ultrasound, or VV treatments; however, there was a significant reduction in marrow elements after LPL, HPL, and HSC treatments. Furthermore, HSC more effectively reduced the marrow elements of OCAs in the middle and deep zones compared with LPL (p < 0.0001) and HPL (p < 0.0001). Macroscopic evaluation revealed a significant reduction in blood, lipid, and marrow elements in the subchondral bone after HSC. Micro-CT, histological analyses, and chondrocyte viability results showed that HSC did not damage the subchondral bone and cartilage; however, LPL and HPL may damage the subchondral bone. CONCLUSION: HSC may play an important role in decreasing immunogenicity and therefore potentially increasing the success of OCA transplantation.

Protein structuromics: A new method for protein structure-function crosstalk in glioma.

Glioma is a type of tumor that starts in the glial cells of the brain or spine. Since the 1800s, when the disease was first named, its survival rates have always been unsatisfactory. Despite great advances in molecular biology and traditional treatment methods, many questions regarding cancer occurrence and the underlying mechanism remain to be answered. In this study, we assessed the protein structural features of 20 oncogenes and 20 anti-oncogenes via protein structure and dynamic analysis methods and 3D structural and systematic analyses of the structure-function relationships of proteins. All of these results directly indicate that unfavorable group proteins show more complex structures than favorable group proteins. As the tumor cell microenvironment changes, the balance of oncogene-related and anti-oncogene-related proteins is disrupted, and most of the structures of the two groups of proteins will be disrupted. However, more unfavorable group proteins will maintain and refold to achieve their correct shape faster and perform their functions more quickly than favorable group proteins, and the former thus support cancer development. We hope that these analyses will help promote mechanistic research and the development of new treatments for glioma.

Identification of lncRNA-miRNA-mRNA Networks in the Lenticular Nucleus Region of the Brain Contributes to Hepatolenticular Degeneration Pathogenesis and Therapy.

Long non-coding RNAs (lncRNAs) are a recently discovered group of non-coding RNAs that play a crucial role in the regulation of various human diseases, especially in the study of nervous system diseases which has garnered significant attention. However, there is limited knowledge on the identification and function of lncRNAs in hepatolenticular degeneration (HLD). The objective of this study was to identify novel lncRNAs and determine their involvement in the networks associated with HLD. We conducted a comprehensive analysis of RNA sequencing (RNA-seq) data, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and computational biology to identify novel lncRNAs and explore their potential mechanisms in HLD. We identified 212 differently expressed lncRNAs, with 98 upregulated and 114 downregulated. Additionally, 32 differently expressed mRNAs were found, with 15 upregulated and 17 downregulated. We obtained a total of 1131 pairs of co-expressed lncRNAs and mRNAs by Pearson correlation test and prediction and annotation of the lncRNA-targeted miRNA-mRNA network. The differential lncRNAs identified in this study were found to be involved in various biological functions and signaling pathways. These include translational initiation, motor learning, locomotors behavior, dioxygenase activity, integral component of postsynaptic membrane, neuroactive ligand-receptor interaction, nuclear factor-kappa B (NF-κB) signaling pathway, cholinergic synapse, sphingolipid signaling pathway, and Parkinson's disease signaling pathway, as revealed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Six lncRNAs, including XR_001782921.1 (P < 0.01), XR_ 001780581.1 (P < 0.01), ENSMUST_00000207119 (P < 0.01), XR_865512.2 (P < 0.01), TCONS_00005916 (P < 0.01), and TCONS_00020683 (P < 0.01), showed significant differences in expression levels between the model group and normal group by RT-qPCR. Among these, four lncRNAs (TCONS_00020683, XR_865512.2, XR_001780581.1, and ENSMUST00000207119) displayed a high degree of conservation. This study provides a unique perspective for the pathogenesis and therapy of HLD by constructing the lncRNA-miRNA-mRNA network. This insight provides a foundation for future exploration in this field.

A chorea-acanthocytosis patient with novel mutations in the VPS13A gene without acanthocyte.

Chorea-acanthocytosis (ChAc) is a rare clinical genetic disorder of the nervous system, which is characterized by choreiform movement disorder, cognitive decline, and psychiatric disorders. ChAc is mostly diagnosed based on its typical clinical manifestations and the increased number of acanthocytes in peripheral blood smears. Here, we report a patient, who has the characteristic clinical manifestations of ChAc with limb choreiform movements, involuntary lip and tongue bites, seizures, and emotional instability. However, her blood smear was negative for acanthocytes with scanning electron microscopy. We later identified two novel pathogenic mutations in the patient's vacuolar protein sorting homolog 13 A (VPS13A) on chromosome 9q21 by targeted gene sequencing, and she was definitively diagnosed with "ChAc." After treatment with carbamazepine, haloperidol, the patient's symptoms gradually improved. We consider that an acanthocyte negative blood smear cannot rule out ChAC diagnosis, and genetic testing is the "gold standard" for the diagnosis. Through a review of previous research, it is rare for a patient to have a clear diagnosis of ChAc by genetic testing, but whose blood smear is negative for acanthocytes with electron microscopy. In addition, in this report, we discovered two novel pathogenic mutations, which have not been reported previously, and extended the genetic characteristics of ChAc.

Case Report: Laparoscopy-assisted resection for intra-abdominal gossypiboma masquerading as a jejunal tumor (with video).

Introduction: Intra-abdominal gossypiboma, a cotton-based retained foreign body after an abdominal surgery, is associated with various clinical manifestations and complications. Its infrequent occurrence and unpredictability make its early diagnosis particularly challenging. We herein present an atypical case of intra-abdominal gossypiboma mistaken for a jejunal tumor. Case presentation: A 33-year-old female presented to the emergency room with an acute episode of progressive abdominal pain and distention, nausea, and vomiting for 20 hours. She had undergone an urgent cesarean section due to fetal tachycardia seven years prior. The initial diagnosis of small bowel obstruction (SBO) due to a jejunal tumor was established by computed tomography. Subsequent to successful medical management of the SBO, a laparoscopy-assisted resection of the mass and the adherent jejunal segment was conducted, culminating in a primary side-to-side jejunojejunostomy. Examination of the excised tissue revealed an approximately spherical fibrous mass, 6 × 6 × 5 cm in dimension, embedded in the jejunal wall, housing a 20 × 20-cm gauze. Postoperative recovery and routine follow-up ensued without complications. Conclusion: In light of this case, the need for clinicians to maintain an elevated awareness and suspicion of gossypiboma should be accentuated when evaluating an intra-abdominal mass, especially in patients with a prior history of high-risk laparotomy. Laparoscopic surgery stands out as a technically proficient and minimally invasive strategy for diagnosing and treating intra-abdominal gossypiboma. Besides, it is imperative to emphasize the importance of meticulous surgical procedures and postoperative protocols to prevent such oversights, reaffirming the need for consistent intraoperative counts and checks of surgical items.

A Dual-Scale Lead-Separated Transformer for ECG Classification.

This work proposes a novel dual-scale lead-separated transformer for the auxiliary diagnosis of 12-lead electrocardiograms (ECGs). We added a new structure design on the basis of traditional ECG signal processing, which led to our model with only 2.6M parameters. The output of the system is the classification results. The fixed 0.5 second ECG segments of each lead are interpreted as independent patches. Together with the reduced dimension signal, patches form a dual-scale representation. As a method to reduce interference from segments with low correlation, a lead-orthogonal attention module is proposed. Experimental results show the effectiveness and scalability of our model.Clinical relevance- Our method improves the scores of clinical 12-lead ECG classification and shows generalization ability. Our model is suitable for single-label and multi-label classification tasks on clinical 12-lead ECG and is compatible with single lead classification. The integration of clinical information can further improve the effectiveness of the model.