Objective To observe the correlations between left atrial myocardial strain and left ventricular function in children with Duchenne muscular dystrophy(DMD).Methods Fifty-one DMD children(DMD group)and 42 healthy one(control group)were prospectively enrolled.The parameters of routine ultrasound and three-dimensional speckle-tracking echocardiography(3D-STE)were compared between groups,and the correlations between left atrial strain parameters and left ventricular function parameters were analyzed.Results The mitral annular lateral wall velocity(e'),left ventricular ejection fraction(LVEF),left atrial ejection fraction(LAEF),left atrioventricular coupling index(LACI),left ventricular global longitudinal strain(LVGLS),left atrial strain during reservoir phase(LASr)and left atrial strain during conduit phase(LAScd)were all lower,while mitral early diastolic peak flow velocity/e'(E/e'),left atrial stiffness index(LASI)and left atrial filling index(LAFI)were higher in DMD group than those in control group(all P＜0.05).In DMD group,LAEF,LASr and LAScd were moderately positively correlated with LVGLS(r=0.409,0.437,0.440,all P＜0.05),LAFI and LASI were weakly negatively correlated with LVGLS(r=-0.207,-0.223,both P＜0.05),while LASr was moderately positively correlated with e'(r=0.419,P＜0.05).Conclusion The left atrial myocardial strain was correlated with left ventricular systolic and diastolic function in DMD children.

The grade of histological severity is a determining factor to evaluate the prognosis and survival rate in primary biliary cholangitis (PBC). However, liver biopsy is limited by sampling error, invasiveness, high cost, and poor compliance. Therefore, in order to overcome the limitations of liver biopsy, some non-invasive evaluation methods have been studied and applied to evaluate the progression of liver fibrosis in PBC. The prognostic score can be calculated using routine laboratory test results obtained at the time of diagnosis, which are characterized by their simplicity, affordability, ease of acquisition, and superior reproducibility. Recent studies have reported that the prognostic score can be employed as a non-invasive liver fibrosis model to diagnose the liver fibrosis stage in PBC and predict the transplant-free survival rate, in addition to being used to evaluate the patient prognosis and transplant-free survival (TFS). This paper reviews, summarizes, and explores the research progress of different prognostic scores as non-invasive liver fibrosis models via their diagnostic performance and predictive accuracy for PBC.

BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

The global incidence of head and neck cancer (HNC) is rising, with over 60% of patients presenting at a locally advanced stage. Radiotherapy remains a cornerstone of HNC treatment, and advancements in modern techniques and concurrent chemotherapy have improved local control and survival rates of HNC patients. However, these benefits also bring challenges in the management of toxicities. Due to the proximity of salivary glands and tumors, especially the highly radiosensitive parotid and submandibular glands, this condition is among the most common adverse effects of radiotherapy. Radiation damages acinar cells and ducts, causing glandular atrophy, fibrosis, and reduced saliva secretion, thereby leading to xerostomia and related complications. The risk and severity of injury are associated with the radiation dose and volume affecting the glands. Prevention and management strategies emphasize precise radiotherapy planning, target optimization, and supportive care. Emerging multimodal imaging techniques offer potential for non-invasive prediction and early diagnosis and treatment of radiation-induced salivary gland injury. Future research in regenerative medicine, tissue engineering, and molecular biology aims to elucidate molecular mechanisms, such as signaling pathways and genomics, facilitating personalized strategies to mitigate radiotherapy-induced toxicities and enhance the quality of life of patients.

A method that integrates the features of image patches from corneal lesions and conjunctival congestion-like complications is proposed to address the limitations of manual keratitis diagnosis(i.e.,time-consuming,laborious,high subjectivity)and the generally low accuracy of automatic keratitis diagnosis based on original slit-lamp images.Specifically,samples are acquired from the corneal and conjunctival regions.A cost-sensitive convolutional neural network is then used to extract and concatenate the high-level features of these image patches.After dimensionality reduction through principal component analysis,the processed features are input into the fully connected layer for classification.Trained and evaluated on 6414 slit-lamp images collected from Ningbo Eye Hospital,the proposed method achieves accuracies of 97.8%,98.6%,and 97.0%for keratitis,normal cornea,and other abnormal corneas,respectively.This method effectively integrates relevant features and provides a feasible solution for high-accuracy keratitis diagnosis.

Stroke is characterized by a high disability rate. After stroke, patients will have different degrees of limb dysfunction, which seriously affects their quality of life. In recent years, fully immersive virtual technology has been gradually applied at home and abroad to promote limb function rehabilitation of stroke patients. This paper reviews the technical components, application forms, application effects, prospects and challenges of fully immersive virtual reality technology in limb function rehabilitation of stroke patients, in order to provide theoretical basis for the subsequent application of fully immersive virtual reality technology to improve the level of limb function rehabilitation of stroke patients.

Objective To observe the correlations between left atrial myocardial strain and left ventricular function in children with Duchenne muscular dystrophy(DMD).Methods Fifty-one DMD children(DMD group)and 42 healthy one(control group)were prospectively enrolled.The parameters of routine ultrasound and three-dimensional speckle-tracking echocardiography(3D-STE)were compared between groups,and the correlations between left atrial strain parameters and left ventricular function parameters were analyzed.Results The mitral annular lateral wall velocity(e'),left ventricular ejection fraction(LVEF),left atrial ejection fraction(LAEF),left atrioventricular coupling index(LACI),left ventricular global longitudinal strain(LVGLS),left atrial strain during reservoir phase(LASr)and left atrial strain during conduit phase(LAScd)were all lower,while mitral early diastolic peak flow velocity/e'(E/e'),left atrial stiffness index(LASI)and left atrial filling index(LAFI)were higher in DMD group than those in control group(all P＜0.05).In DMD group,LAEF,LASr and LAScd were moderately positively correlated with LVGLS(r=0.409,0.437,0.440,all P＜0.05),LAFI and LASI were weakly negatively correlated with LVGLS(r=-0.207,-0.223,both P＜0.05),while LASr was moderately positively correlated with e'(r=0.419,P＜0.05).Conclusion The left atrial myocardial strain was correlated with left ventricular systolic and diastolic function in DMD children.

A method that integrates the features of image patches from corneal lesions and conjunctival congestion-like complications is proposed to address the limitations of manual keratitis diagnosis(i.e.,time-consuming,laborious,high subjectivity)and the generally low accuracy of automatic keratitis diagnosis based on original slit-lamp images.Specifically,samples are acquired from the corneal and conjunctival regions.A cost-sensitive convolutional neural network is then used to extract and concatenate the high-level features of these image patches.After dimensionality reduction through principal component analysis,the processed features are input into the fully connected layer for classification.Trained and evaluated on 6414 slit-lamp images collected from Ningbo Eye Hospital,the proposed method achieves accuracies of 97.8%,98.6%,and 97.0%for keratitis,normal cornea,and other abnormal corneas,respectively.This method effectively integrates relevant features and provides a feasible solution for high-accuracy keratitis diagnosis.

Stroke is characterized by a high disability rate. After stroke, patients will have different degrees of limb dysfunction, which seriously affects their quality of life. In recent years, fully immersive virtual technology has been gradually applied at home and abroad to promote limb function rehabilitation of stroke patients. This paper reviews the technical components, application forms, application effects, prospects and challenges of fully immersive virtual reality technology in limb function rehabilitation of stroke patients, in order to provide theoretical basis for the subsequent application of fully immersive virtual reality technology to improve the level of limb function rehabilitation of stroke patients.