Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.