Objective To investigate the risk factors for abnormal cardiac function in patients with hepatolenticular degeneration （also known as Wilson disease ，WD） using cardiac magnetic resonance imaging （CMR）， and to identify indicators with a value for early diagnosis. Methods Patients diagnosed with WD were randomly selected to undergo CMR examination， and based on CMR findings， they were divided into abnormal group and normal group. A univariate analysis was used to obtain potential risk factors， then a multivariate logistic regression analysis was performed for variables with a significant difference， and finally the receiver operating characteristic （ROC） curve analysis was performed for the independent risk factors identified. Results A total of 42 WD patients were enrolled， with 21 in the abnormal CMR group and 21 in the normal CMR group. Compared with the normal CMR group， the abnormal CMR group had a significantly higher age and significantly higher levels of total bilirubin， serum copper， and peak 24-hour urinary copper during treatment. The multivariate Logistic regression analysis showed that white blood cell count （WBC） （OR=2.927， 95%CI 1.127‒7.839， P=0.028）， serum copper（OR=3.822， 95%CI 1.108‒13.178， P=0.034）， and type Ⅳ collagen （OR=1.097， 95%CI 1.011‒1.191，P=0.027） were independent risk factors for CMR abnormalities in WD patients. The ROC curve analysis showed that among the above three indicators used alone， serum copper had the highest diagnostic value with an area under the ROC curve （AUC） of 0.713， followed by WBC（AUC=0.651） and type Ⅳ collagen （AUC=0.644）， and the combination of these three indicators had significantly higher diagnostic efficacy （AUC=0.869）. Conclusion Serum copper is the single indicator with the highest diagnostic efficacy for CMR abnormalities in WD patients， but the combination of serum copper， WBC， and type Ⅳ collagen has a significantly better diagnostic value in identifying abnormal cardiac function in WD patients.

Objective To investigate the clinical features and key diagnostic points of aceruloplasminemia （ACP）， as well as the features of a novel pathogenic mutation. Methods A systematic analysis was performed for the clinical data of one patient with a confirmed diagnosis of ACP， and a literature review was performed based on related articles in China and globally. Results Based on the clinical features of this patient and the analysis of the family， it was clarified that the homozygous c.1944C>G （p.Ser648Arg） mutation in the Ceruloplasmin （CP） gene could cause ACP and was reported for the first time worldwide. Conclusion ACP is an extremely rare autosomal recessive disease due to abnormal iron metabolism caused by a significant reduction in ceruloplasmin， with the main clinical manifestations of retinopathy， diabetes， ataxia， and cognitive impairment， and genetic testing of the CPgene has a relatively high diagnostic value.
Ceruloplasmin

The prevalence of dry eye among children has been progressively increasing each year; however, clinical diagnosis remains challenging due to the unique physiological attributes of the pediatric tear film functional unit, as well as symptoms that are often atypical and clinical signs that differ from those seen in adults. In healthy children, tear secretion is generally greater, the meibomian gland structure is typically more intact, and the meibum composition and physicochemical properties are more favorable for the maintenance of tear film stability. Compared to adults, the etiology of pediatric dry eye is more frequently associated with meibomian gland dysfunction, allergic ocular conditions, orthokeratology lens wear, environmental influences, such as growing screen time, and systemic disorders. Affected children frequently exhibit non-specific symptoms such as excessive blinking or rubbing of the eyes, which may be overlooked due to their limited ability to verbalize discomfort. Clinical signs can include conjunctival hyperemia, decreased tear meniscus height, and corneal epithelial punctate lesions, though these tend to be milder or less distinct compared with adults. Diagnostic requires the use of age-appropriate tear metrics, such as the Schirmer test and tear film breakup time, alongside ocular surface evaluation, with particular attention to features specific to children that distinguish it from dry eye in adults. Going forward, it is essential to establish and validate pediatric-specific diagnostic criteria to improve ocular surface health and maximize visual quality in this vulnerable population.

Hereditary carotid body tumor (HCBT) is a rare neuroendocrine tumor mainly caused by germline mutations of the SDHx gene. Its multifocality, familial aggregation, and potential malignant risk pose unique challenges to diagnosis and treatment. This review systematically expounds the molecular mechanism of HCBT, pointing out that SDHx mutations drive tumorigenesis through the “pseudo-hypoxia” pathway and are regulated by epigenetic and somatic mutations. In terms of diagnosis, we emphasize the crucial role of ⁶⁸Ga-DOTATATE PET/CT and SDHB immunohistochemistry and advocate for multigene panel sequencing for patients with high-risk characteristics (such as early-onset, multifocal, family history or malignant signs) to clarify the genetic background. On the basis of existing evidence, we recommend conducting baseline biochemical tests for all newly diagnosed patients and actively suggest genetic screening for high-risk individuals such as those who are young, have multifocal tumors, or have a family history. In terms of treatment, surgery is the main treatment method for HCBT. Nevertheless, individualized strategies still need to be formulated based on tumor classification and patient’s overall condition and genetic background. Comprehensive management measures such as targeted therapy, radionuclide therapy, and standardized family management are crucial for improving the prognosis of patients.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

Kidney stones are a typical model of pathological mineralization, and the association between local mineralization imbalance and systemic ectopic calcification is complex. This review systematically summarizes three major advances in the field. Firstly, at the molecular level, inflammatory/immune modulation(Th-cell activation), metabolic dysregulation(aberrant calcium-phosphate/lipid metabolism), and epigenetic control(lncRNA-driven osteogenic differentiation)act in concert to drive Randall's plaque formation. Secondly, at the systemic level, nephrolithiasis shares the Klotho pathway with vascular calcification and bone-metabolic disorders, converging on the inhibition of Wnt/β-catenin and related axes, underscoring the global impact of calcium-phosphate homeostatic disruption. Thirdly, in translational medicine, GeoBioMed technologies dissect mineral heterogeneity, AI models predict recurrence risk(AUC=0.87), CRISPR-based interventions [silencing of metastasisassociated lung adenocarcinoma transcript 1(MALAT1)], and biomimetic materials(carbonate-apatite coatings)exhibit significant therapeutic promise. Future efforts should integrate single-cell multi-omics, microbiome modulation, and cross-organ dynamic monitoring to shift the therapeutic paradigm from stone removal to the precise restoration of mineralization homeostasis.

Objective: To evaluate the clinical efficacy and safety of micro-percutaneous nephrolithotomy (microPCNL) using Needle-perc in the oblique supine-lithotomy position for treating 1—2 cm lower-pole stones (LPSs)，by comparing it with flexible ureteroscopic lithotripsy (FURL)，so as to identify an effective surgical method for LPSs. Methods: We retrospectively analyzed the clinical data of 56 patients with isolated LPSs of 1—2 cm treated in our hospital during Jan.and Dec.2023.Patients were divided into two groups based on the treatment method：FURL (n=31) and microPCNL (n=25).General information and perioperative data were compared between the two groups. Results: All operations were successfully completed.The operation time was shorter in the microPCNL group than in the FURL group \[(46.5±10.1) min vs.(73.5±18.9) min，P<0.001\].Stone-free rate (SFR) was 92.0% in the microPCNL group and 71.0% in the FURL group (P=0.026).There were no significant differences in the average fall of hemoglobin level，serumc creatinine change level，hospitalization time and postoperative fever between the two groups. Conclusion: MicroPCNL in oblique supine-lithotomy position is a safe and effective treatment for 1-2 cm LPSs，with a higher SFR compared to FURL.

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Resveratrol(Res) is a kind of polyphenolic compound, possessing multiple biological activities such as antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. In recent years, the cardiovascular protective mechanism of Res has become a research hotspot. Studies have shown that Res has a protective effect on the cardiovascular system through various pathways, such as inhibiting oxidative stress, regulating ferroptosis of cells, improving ischemia-reperfusion(I/R) injury, regulating lipid metabolism, suppressing inflammatory responses, and enhancing endothelial function. It can also alleviate cardiotoxicity caused by drugs and chemicals. In terms of oxidative stress, Res reduces the level of intracellular reactive oxygen species(ROS) by enhancing the expression of proteins such as silent information regulator 1(SIRT1) and regulating mitochondrial function, thereby alleviating myocardial cell damage. Regarding ferroptosis, Res inhibits the occurrence of ferroptosis by regulating the expression of proteins related to iron metabolism. Res can also improve I/R injury through mechanisms such as activating autophagy and the mitochondrial quality control network. In regard to improving endothelial function, Res protects the function of endothelial cells by regulating multiple signaling pathways, such as downregulating the PREP1-mediated pathway. Res can also regulate lipid metabolism and inhibit the progression of atherosclerosis. In terms of inflammatory responses, Res exerts anti-inflammatory effects through mechanisms such as inhibiting the nuclear factor-kappa B(NF-κB) signaling pathway. In addition, Res has an improving effect on cardiotoxicity caused by different drugs or environmental factors. However, the clinical application of Res still faces limitations such as poor pharmacokinetic properties. In the future, in-depth exploration is needed at multiple levels from basic research to clinical application to clarify the dose-response relationship and standardize the standards of medication regimens with the expectation of providing more effective strategies for the prevention and treatment of cardiovascular diseases.
Humans ; Resveratrol/pharmacology* ; Animals ; Cardiotonic Agents/pharmacology* ; Oxidative Stress/drug effects* ; Cardiovascular Diseases/genetics* ; Cardiovascular System/metabolism* ; Signal Transduction/drug effects*