OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.

Objective:To investigate the impact of programmed death receptor-1(PD-1)and its ligand(PD-L1)on the differentiation of decidual macrophages(DMs)and embryonic development.Methods:20 patients with re-current spontaneous abortion(RSA group)and 20 patients with normal pregnancy induced artificial abortion(NP group)were selected from Sichuan Provincial People's Hospital between March 2021 and January 2024.Villous and decidual tissues were obtained from both groups.Real-time fluorescent quantitative polymerase chain reac-tion(qPCR)and Western blot techniques were used to detect the expression of PD-L1 mRNA and protein in vil-lous tissues.Flow cytometry was used to analyze the types of DMs and their PD-1 expression.Human monocytic leukemia cells(THP-1)were differentiated under different conditions,with a control group and a PD-1 blocked group established,and different reagents were added into those two groups to induce differentiation,then the pro-portion of DMs types was measured in both groups.Results:PD-L1 protein and mRNA were expressed in the vil-lous tissue of both groups of patients but the expression of PD-L1 protein and mRNA was reduced in the RSA group compared to the NP group(P<0.05).The decidual tissues of both groups contained M1 and M2 macro-phages.Compared with the NP group,the ratio of M2 to M1 DMs in the RSA group was lower(P<0.05),indica-ting a polarization towards the M1 type in DMs.There was no statistically significant difference in PD-1 expression between the two groups(P>0.05).Human THP-1 cells can be stimulated to differentiate into M1 and M2 macro-phages.Afterblocking PD-1,theratioof M2 to M1 macrophages decreased(P<0.05),indicating a polarization towards the M1 type in macrophages.Conclusions:In patients with RSA,the expression of PD-L1 in villous tis-sues is decreased,and DMs polarize towards the M1 type.Blocking the PD-1/PD-L1 pathway can further promote the polarization of macrophages towards the M1 type.The influence of PD-1/PD-L1 pathway on macrophage po-larization may provide new insights into the pathogenesis of RSA.