Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.