Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

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/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/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.

An excess of amyloid beta (Aβ) led to a rise in ROS production, which in turn caused inflammatory reactions and mitochondrial dysfunction, both of which accelerate the progression of Alzheimer’s disease (AD).Natural flavonoids are proposed as possible agents for neurodegeneration. Pectolinarin is an important flavone mainly found in Cirsium species. In this study, we explored the potential neuroprotective effect of pectolinarin in Aβ25-35 -induced SH-SY5Y cells. The result demonstrated that pectolinarin enhanced cell viability. Pectolinarin treatment inhibited Aβ25-35 -induced ROS generation. Pectolinarin also suppressed NO generation by inhibiting the translocation of NF-ĸB and downregulating protein expression of iNOS and COX-2. Moreover, the expression of Bcl-2 increased while BAX protein decreased when the cells were exposed to pectolinarin, resulting in a decrease in the BAX/Bcl-2 ratio. Pectolinarin treatment also increased BDNF and its receptor TrkB protein expression. In conclusion, pectolinarin neuroprotected Aβ25-35 -induced inflammation and apoptosis. These findings suggest that pectolinarin may be a promising neuroprotective functional food in the protection of the neurodegenerative diseases, including AD.

An excess of amyloid beta (Aβ) led to a rise in ROS production, which in turn caused inflammatory reactions and mitochondrial dysfunction, both of which accelerate the progression of Alzheimer’s disease (AD).Natural flavonoids are proposed as possible agents for neurodegeneration. Pectolinarin is an important flavone mainly found in Cirsium species. In this study, we explored the potential neuroprotective effect of pectolinarin in Aβ25-35 -induced SH-SY5Y cells. The result demonstrated that pectolinarin enhanced cell viability. Pectolinarin treatment inhibited Aβ25-35 -induced ROS generation. Pectolinarin also suppressed NO generation by inhibiting the translocation of NF-ĸB and downregulating protein expression of iNOS and COX-2. Moreover, the expression of Bcl-2 increased while BAX protein decreased when the cells were exposed to pectolinarin, resulting in a decrease in the BAX/Bcl-2 ratio. Pectolinarin treatment also increased BDNF and its receptor TrkB protein expression. In conclusion, pectolinarin neuroprotected Aβ25-35 -induced inflammation and apoptosis. These findings suggest that pectolinarin may be a promising neuroprotective functional food in the protection of the neurodegenerative diseases, including AD.

An excess of amyloid beta (Aβ) led to a rise in ROS production, which in turn caused inflammatory reactions and mitochondrial dysfunction, both of which accelerate the progression of Alzheimer’s disease (AD).Natural flavonoids are proposed as possible agents for neurodegeneration. Pectolinarin is an important flavone mainly found in Cirsium species. In this study, we explored the potential neuroprotective effect of pectolinarin in Aβ25-35 -induced SH-SY5Y cells. The result demonstrated that pectolinarin enhanced cell viability. Pectolinarin treatment inhibited Aβ25-35 -induced ROS generation. Pectolinarin also suppressed NO generation by inhibiting the translocation of NF-ĸB and downregulating protein expression of iNOS and COX-2. Moreover, the expression of Bcl-2 increased while BAX protein decreased when the cells were exposed to pectolinarin, resulting in a decrease in the BAX/Bcl-2 ratio. Pectolinarin treatment also increased BDNF and its receptor TrkB protein expression. In conclusion, pectolinarin neuroprotected Aβ25-35 -induced inflammation and apoptosis. These findings suggest that pectolinarin may be a promising neuroprotective functional food in the protection of the neurodegenerative diseases, including AD.

An excess of amyloid beta (Aβ) led to a rise in ROS production, which in turn caused inflammatory reactions and mitochondrial dysfunction, both of which accelerate the progression of Alzheimer’s disease (AD).Natural flavonoids are proposed as possible agents for neurodegeneration. Pectolinarin is an important flavone mainly found in Cirsium species. In this study, we explored the potential neuroprotective effect of pectolinarin in Aβ25-35 -induced SH-SY5Y cells. The result demonstrated that pectolinarin enhanced cell viability. Pectolinarin treatment inhibited Aβ25-35 -induced ROS generation. Pectolinarin also suppressed NO generation by inhibiting the translocation of NF-ĸB and downregulating protein expression of iNOS and COX-2. Moreover, the expression of Bcl-2 increased while BAX protein decreased when the cells were exposed to pectolinarin, resulting in a decrease in the BAX/Bcl-2 ratio. Pectolinarin treatment also increased BDNF and its receptor TrkB protein expression. In conclusion, pectolinarin neuroprotected Aβ25-35 -induced inflammation and apoptosis. These findings suggest that pectolinarin may be a promising neuroprotective functional food in the protection of the neurodegenerative diseases, including AD.

An excess of amyloid beta (Aβ) led to a rise in ROS production, which in turn caused inflammatory reactions and mitochondrial dysfunction, both of which accelerate the progression of Alzheimer’s disease (AD).Natural flavonoids are proposed as possible agents for neurodegeneration. Pectolinarin is an important flavone mainly found in Cirsium species. In this study, we explored the potential neuroprotective effect of pectolinarin in Aβ25-35 -induced SH-SY5Y cells. The result demonstrated that pectolinarin enhanced cell viability. Pectolinarin treatment inhibited Aβ25-35 -induced ROS generation. Pectolinarin also suppressed NO generation by inhibiting the translocation of NF-ĸB and downregulating protein expression of iNOS and COX-2. Moreover, the expression of Bcl-2 increased while BAX protein decreased when the cells were exposed to pectolinarin, resulting in a decrease in the BAX/Bcl-2 ratio. Pectolinarin treatment also increased BDNF and its receptor TrkB protein expression. In conclusion, pectolinarin neuroprotected Aβ25-35 -induced inflammation and apoptosis. These findings suggest that pectolinarin may be a promising neuroprotective functional food in the protection of the neurodegenerative diseases, including AD.

BACKGROUND/OBJECTIVES: There is growing interest in herbal medicines for managing age-related diseases, such as Alzheimer's and Parkinson’s. Safflower seeds (Carthamus tinctorius L. seeds, CTS) and dandelions (Taraxacum coreanum, TC) are widely used to treat bone- or inflammation-related diseases in Oriental countries. This study investigated the protective effect of the CTS–TC combination on scopolamine (Sco)-induced memory deficits through inflammatory response and cholinergic function. Moreover, marker components such as serotonin, N-(p-coumaroyl) serotonin, N-feruloylserotonin, chlorogenic acid, and chicoric acid in the CTS–TC combination were analyzed for their potential benefits on memory function.MATERIALS/METHODS: Water extracts of CTS, TC, and the CTS–TC combination at various ratios (4:1, 1:1, and 1:4) (100 mg/kg) were orally administered to mice for 14 days. Sco (1 mg/kg) was intraperitoneally injected into the mice before each behavioral test. T-maze and novel object recognition tests were conducted to monitor behavioral changes after the treatment.Western blotting was performed to detect protein expression. In addition, the presence of 5 biomarkers, serotonin, N-(p-coumaroyl) serotonin, N-feruloylserotonin, chlorogenic acid, and chicoric acid, was analyzed using high-performance liquid chromatography (HPLC). RESULTS: Behavioral tests showed that the CTS–TC combination enhanced memory function in Sco-injected mice. Inflammation-related proteins (inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein) were downregulated after treatment with the CTS–TC combination. The acetylcholinesterase protein expression was also downregulated.HPLC analysis revealed that N-feruloylserotonin and chicoric acid were the predominant components, followed by N-(p-coumaroyl) serotonin, chlorogenic acid, and serotonin. CONCLUSION These findings suggest that the CTS–TC combination protects against Sco-induced memory deficits by inhibiting inflammatory responses and cholinergic dysfunction. N-feruloylserotonin and chicoric acid, along with N-(p-coumaroyl) serotonin, chlorogenic acid, and serotonin, might be biomarkers for the CTS–TC combination, and their effects on memory protection warrant further study.