A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Objective To explore the predictive value of radiomics for postoperative pancreatic fistula, infection, and long-term survival in patients with pancreatic ductal adenocarcinoma (PDAC). Methods 206 patients who received radical resection of pancreatic cancer in Zhongshan Hospital, Fudan University from January 2014 to December 2020 and were pathologically confirmed as PDAC after surgery were retrospectively selected, all of whom had complete surgical data and long-term follow-up data. Pyradiomics was used to analyze the enhanced CT images of all patients and extract radiomics features. LASSO dimensionality reduction combined with logistic regression analysis was used to construct a predictive model for pancreatic fistula and abdominal infection after PDAC surgery, and evaluating the model’s effectiveness using ROC curves. A long-term survival prediction model for PDAC patients was constructed using LASSO dimensionality reduction combined with Cox regression analysis, and patient risk scores were calculated. The patients were divided into high-risk and low-risk groups based on the median, and the survival curves were compared to evaluate the effectiveness of the model. The imaging omics features with the highest weight were divided into high expression group and low expression group according to the median, and the prognostic differences and clinical features were compared. Radiomics and clinical features were combined to analyze the influencing factors of long-term prognosis and construct a clinical imaging comprehensive model. Results A total of 1 595 radiomics features were extracted. A predictive model for pancreatic fistula and infection after PDAC surgery was constructed, with AUC values of 0.81 and 0.79, respectively. The PDAC long-term survival prediction model was successfully constructed, and the prognosis of the high-risk group was worse than that of the low-risk group (P<0.001). The weight of the radiomics feature “log-sigma-5-mm-3D_glszm_ZonePercentage” was 59.557. The CA19-9 level in the high expression group is higher than that in the low expression group (P=0.017), and there is a statistically significant difference in survival curves between the two groups (P=0.021). The comprehensive clinical imaging model suggested that age, AJCC stage, lymph infiltration, CA19-9 level and imaging characteristics were risk factors for long-term prognosis of PDAC patients (HR=1.028, 4.084, 2.566, 1.232 and 2.536). Conclusions The predictive model based on radiomics has good predictive performance for pancreatic fistula, infection, and long-term prognosis after PDAC surgery. Patients with high expression of the radiomics feature “log-sigma-5-mm-3D_glszm_ZonePercentage” face poorer prognosis.

Objective To systematically evaluate the performance and methodological quality of the risk prediction models for urinary incontinence after radical prostatectomy,so as to provide a reference for selecting the appropriate risk prediction tool.Methods A systematic search was conducted in PubMed,Web of Science,Cochrane Library,CINAHL,EMBASE,CNKI,Wanfang,VIP,and Chinese biomedical literature database from inception to Jan.23,2024.Two researchers independently conducted literature screening and data extraction,and the prediction model risk of bias assessment tool(PROBAST)was applied to assess the risk of bias and applicability of the included studies.MedCalc software was used to perform a meta-analysis of the area under curve(AUC)of the validation groups using the random effect model,and the publication bias and sensitivity analysis were also performed.Results A total of 8 studies were included,with a combined sample size of 7 216 cases.Six models reported the AUC values,and 7 models reported calibration.The applicability of 2 studies was acceptable,while 6 were poor.The most commonly used type of prediction model was logistic regression.After excluding models with extreme AUC values,the random-effects meta-analysis result was 0.840(95%confidence interval 0.786 to 0.895),with no heterogeneity(I2=0%,P=0.737).The bias risk was high in all 8 studies,mainly due to retrospective cohort data,transformation of continuous variables into binary variables,unaddressed missing data,selection of predictors based on univariate analysis,incomplete report of the model discrimination and calibration,and lack of external validation.Egger test result indicated no significant publication bias.Conclusion The development and validation process of the existing risk prediction models for urinary incontinence after radical prostatectomy is still imperfect.Future research should construct prediction models based on multicenter and large-sample data,strengthen the clinical applicability assessment of the models,and strictly follow the reporting standards and procedures,so as to establish high-quality risk prediction models for clinical practice.

Objective To explore the histological and immunohistochemical characteristics of undifferentiated liver cancer in small tissue biopsy specimens.Methods Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)was used to obtain liver tissue strips and cell samples.The tissue and cell morphology of a case of liver undifferentiated carcinoma were analyzed by hematoxylin-eosin staining,immunohistochemical staining,and cell smear techniques.The related literatures of undifferentiated liver cancer were retrieved from PubMed and Wanfang databases to summarize the diagnostic criteria of undifferentiated liver cancer.Results Histologically,this case of undifferentiated liver cancer presented as a patchy arrangement of oval or spindle shaped tumor cells,with large,deeply stained,and distinctly atypical anaplastic cells visible in between.Localized nuclear fission images could be observed.The cytological manifestation was nuclear atypical cells,with less cytoplasm in atypical cells,and some cells had red staining of cytoplasm resembling squamous cell carcinoma cytoplasm.The immunohistochemical results showed epithelial membrane antigen(EMA)(+),cytokeratin(CK)18(+),glutamine synthetase(GS)(-),carbohydrate antigen 19-9(CA19-9)(-),vimentin(-),CK7(-),CK20(-),alpha fetoprotein(AFP)(-),glypican 3(Gpc-3)(-),hepatocellular paraffin antigen-1(Hep-1)(-),and chromogranin A(CgA)(-).The results of literature review showed that undifferentiated liver cancer was more common in middle-aged and elderly men,and generally appeared as isolated circular nodules.In 8 out of 9 cases,tumor cells were observed to grow diffusely under the microscope,and no typical glandular or beam like growth patterns of liver tumors were observed.The malignant degree of tumor cells was high,with 5 out of 9 cases showing significantly atypical interstitial cells.Immunohistochemical features included positive expression of epithelial derived markers(such as pan cytokeratin[CKpan],EMA,and CK18)and negative expression of liver derived markers(AFP,Hep-1,Gpc-3,and arginase-1),which might be accompanied by positive expression of neuroendocrine markers.Conclusion The histological morphology of undifferentiated liver cancer is characterized by diffuse distribution of anaplastic cells,without any glandular or cord like arrangement.The tumor often expresses epithelial derived markers,while liver derived markers show negative expression.