Objective: To analyze the serological phenotypes and molecular genetic characteristics of a proband with ABO forward and reverse typing discrepancy and their family members, and to investigate the molecular genetic mechanism underlying the Ael/AelB phenotype caused by the c. 575T>C variant on an ABO A1.02 background. Methods: Serological testing and adsorption-elution assays were performed for blood group identification of the proband and family members. PCR-SBT, cloning sequencing, and Nanopore third-generation sequencing were used to analyze ABO gene variants and haplotypes. Phyre2 and PyMOL were used to predict the effect of the p. Ile192Thr variant on the structure of glycosyltransferase A (GTA), and plasma GTA activity was evaluated using an in vitro transferase assay. Results: Among thirteen family members, four members showed a serological phenotype consistent with the Ael subtype and one with the AelB subtype. Cloning sequencing and third-generation sequencing confirmed that five family members carried the ABO A1.02 (c. 575T>C) variant, which co-segregated with the weak A phenotype in the family. Structural modeling suggested that p. Ile192Thr may alter the local spatial conformation and hydrogen-bond interactions of GTA. Plasma GTA activity testing showed markedly reduced GTA activity in the tested individuals. Conclusion: The ABO A1.02 (c. 575T>C) variant is associated with the Ael/AelB phenotype. The p. Ile192Thr substitution may weaken A antigen expression by altering GTA conformation and reducing enzymatic activity. This study provides additional evidence for the role of this variant in the Ael/AelB phenotype from the perspectives of familial inheritance, full-length haplotype analysis, and functional assessment, which is important for accurate ABO subtype identification and individualized transfusion strategies.

Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

To explore the clinical significance of decreased serum immunoglobulin (Ig) A levels in patients with IgG4-related disease (IgG4-RD).

Objective:To explore the assessment value of ultrasound scoring system combined with shear wave elastography(SWE)on curative effect of IgG4-related submandibular and lacrimal gland inflammation.Methods:This study was a prospective cohort study.A total of 103 patients with IgG4-related submandibular and/or lacrimal gland inflammation who admitted to the Department of Rheumatology and Immunology of Beijing Friendship Hospital,Capital Medical University from September 2022 to December 2024 were consecutively included.They were divided into an effective group(45 cases)and a non-effective group(58 cases)based on the curative effect.All patients were assessed by conventional ultrasound and SWE before and after treatment.Logistic regression analysis was used to determine the independent influencing factors of assessing the curative effect,and then,a receiver operating characteristic(ROC)curve and nomograms were drawn.Results:There were no statistically significant differences in gender and age between the effective group and the non-effective group(P>0.05).The difference between the submandibular and lacrimal gland score,change rate of score,difference of mean Young's modulus(Emean),Emean change rate,difference of maximum value of Young's modulus(Emax),and Emax change rate in the effective group were all higher than those in the non-effective group,and the differences were statistically significant(Z=-7.916,-7.680,-6.767,-6.722,-6.360,-5.957,P<0.05),respectively.The difference between the submandibular and lacrimal gland score(OR=2.90,P<0.001)and the Emax difference(OR=1.18,P<0.05)had diagnostic value for assessing the curative effectiveness.The area under curve(AUC)value,sensitivity,specificity and accuracy of the difference between submandibular and lacrimal gland score were respectively 0.945,88.9%,94.8%and 87.4%in assessing the curative effectiveness.The above indicators of Emax difference were respectively 0.866,86.7%,70.7%and 77.7%in assessing the curative effectiveness.The above indicators of the combination of them were respectively 0.976,93.3%,94.8%and 94.2%.Conclusion:The combination of the conventional ultrasound scoring system and SWE has higher diagnostic value in assessing the curative effect of IgG4-related submandibular and lacrimal gland inflammation.The combined application can significantly improve the accuracy and provide reliable imaging reference for clinical practice.

Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.

Objective·To investigate the clinical,pathological,and molecular genetic features and prognosis of epithelioid hemangioendothelioma(EHE)patients.Methods·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected.Tissue samples were analyzed using hematoxylin-eosin(H-E)staining,immunohistochemistry(IHC),and fluorescence in situ hybridization(FISH).Results·Among the 12 patients,there were 3 males and 9 females,with a mean age of(47.17±11.15)years.Tumors were located in the liver(6 cases),lung(4 cases),mediastinum(1 case),and supraclavicular region(1 case).Nine patients were asymptomatic,while 3 presented with mild symptoms such as chest tightness and fatigue.CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules,and 2 cases had tumors in both organs.Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules.H-E staining demonstrated that tumor tissues were composed of epithelioid,dendritic,and intermediate cells,arranged in acinar,cord-like,or clustered patterns.Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm,with some showing a signet-ring appearance and cytoplasmic vacuoles.The stroma contained a mucoid matrix.IHC staining revealed that mesenchymal endothelial markers,including vimentin,CD31,ETS transcription factor ERG,and factor Ⅷ-related antigen,were positive in the tumor tissues,while epithelial markers showed low positivity with weak staining.The Ki-67 indexes were also low.FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1(CAMTA1)gene break,while 2 patients had a transcription factor E3(TFE3)gene break.Of the 12 patients,11 were followed up for 2 to 38 months,with a mean follow-up time of 21.7 months.Three patients achieved tumor-free survival,6 were alive with tumors,1 died 4 months after surgery,and 1 died of heart disease 24 months after surgery.Conclusion·EHE has atypical clinical features,a tendency to recur,a and variable prognosis.Accurate diagnosis requires a combination of histopathology,IHC,and a molecular testing.

The liver is one of the organs most commonly affected by rheumatic diseases.Hepatic abnormalities in patients with rheumatic diseases can result from a variety of factors,including direct liver involvement by the disease itself,coexistence with primary liver disease,and drug-induced liver injury.When liver indicators are abnormal,a thorough differential diagnosis is required.For unexplained liver dysfunction,routine testing for autoantibodies should be performed to facilitate early identification of underlying autoimmune liver disease.If the etiology remains unclear,a liver biopsy is recommended for a final diagnosis if feasible.Alongside active management of rheumatic diseases,it is necessary to closely monitor liver function,avoid the use of agents that may exacerbate hepatic damage,particularly anti-rheumatic drugs with strong hepatotoxicity,and tailor treatment strategies according to personal specific conditions,so as to minimize liver damage and improve long-term outcome.

Rheumatic diseases are chronic inflammatory autoimmune diseases that can affect multiple organs and systems.In clinical practice,most patients with rheumatic diseases present with asymptomatic liver function abnormalities during the course of the disease,and the etiology of such diseases may be associated with the rheumatic disease itself,medications,metabolism,viruses,or the presence of other chronic liver diseases.Immune-mediated inflammatory responses play a significant role in liver involvement(including hepatocyte injury,intrahepatic vascular lesions,and hepatic fibrosis)in rheumatic diseases.This article discusses the clinical features and management of liver involvement secondary to rheumatic diseases,in order to enhance the understanding of this condition among specialists in related fields.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.