Objective: To explore the active components, key targets, and mechanism of action of turnip in alleviating pulmonary fibrosis(PF) based on network pharmacology and animal experiments. Methods: The active components and targets of Brassica rapa L. were screened using the traditional Chinese medicine systems pharmacology database and analysis platform database, and PF-related targets were obtained from disease databases such as online mendelian inheritance of man(OMIM) and DrugBank. The intersection targets were used to construct a protein-protein interaction(PPI) network to identify core targets, followed by gene oncology(GO)/Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. In the animal experiments, a bleomycin-induced PF mouse model was established. Pathological changes in lung tissue were evaluated using HE and Masson staining. qRT-PCR was used to detect the mRNA expression of tumor necrosis factor-α(TNF-α), phosphatidylinositol 3-kinase(PI3K), and akstrain transforming 1(AKT1), and immunofluorescence staining was used to measure the protein expression of TNF-α, PI3K, and AKT1. Results: The 68 active components identified in Brassica rapa L. may regulate PI3K-Akt signaling pathway by acting on 89 potential targets such as TNF-α and AKT1. The results of animal experiments showed that polysaccharide of Brassica rapa L.(BRPs) could significantly reduce the degree of bleomycin induced pulmonary fibrosis in mice; HE and Masson staining of lung tissue showed that compared with the model group, the damage of alveolar structure, the infiltration of inflammatory cells and the deposition of collagen fibers in the BRPs treatment group were significantly reduced. Further mechanism studies showed that BRPs could significantly down-regulate the mRNA and protein expression levels of TNF-α, PI3K and AKT1 in lung tissue of pulmonary fibrosis mice. Conclusion Brassica rapa L. can synergistically alleviate pulmonary fibrosis through “multi-component, multi-target and multi-channel” approach; BRPs is one of the main active components, and plays an anti-fibrosis role by inhibiting TNF-α/PI3K Akt signaling pathway.

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy (CSF1R-L) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. It is typically characterized by rapidly progressive cognitive decline, motor dysfunction, and psychiatric or behavioral abnormalities, leading to significant disability and early mortality. More than 100 mutations of CSF1R have been identified in CSF1R-L, but the clinical-genotype relationship is unclear. This report describes a case of CSF1R-L that initially presented with atypical symptoms of left lower limb pain, numbness, and weakness. Despite the non-specific presentation, comprehensive imaging data were available throughout the disease course. Genetic testing identified a heterozygous missense mutation in exon 18 of the CSF1R gene (c.2508CA, p.Ser836Arg), a novel variant not previously reported in the literature. This case offers valuable insights into the dynamic progression of cranial MRI changes in CSF1R-L, broadens the genetic spectrum of this disease, enhances awareness among clinicians, and provides crucial information for the early diagnosis of this condition.

Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.There-fore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural com-pounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehen-sive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy (CSF1R-L) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. It is typically characterized by rapidly progressive cognitive decline, motor dysfunction, and psychiatric or behavioral abnormalities, leading to significant disability and early mortality. More than 100 mutations of CSF1R have been identified in CSF1R-L, but the clinical-genotype relationship is unclear. This report describes a case of CSF1R-L that initially presented with atypical symptoms of left lower limb pain, numbness, and weakness. Despite the non-specific presentation, comprehensive imaging data were available throughout the disease course. Genetic testing identified a heterozygous missense mutation in exon 18 of the CSF1R gene (c.2508CA, p.Ser836Arg), a novel variant not previously reported in the literature. This case offers valuable insights into the dynamic progression of cranial MRI changes in CSF1R-L, broadens the genetic spectrum of this disease, enhances awareness among clinicians, and provides crucial information for the early diagnosis of this condition.

OBJECTIVE To investigate the effect of Jianpi Yangzheng(JPYZ)formula regulating tumor-associated macrophage(TAM)exosomes on anoikis in gastric cancer and its mechanism.METHODS TAM model was established by inducing human mononuclear THP-1 cells in vitro;M0,TAM and TAM+JPYZ formula exosomes were extracted by ultracentrifugation and co-incuba-ted with gastric cancer cells.Flow cytometry was used to detect the effect of exosomes in each group on anoikis in gastric cancer cells.A BALB/c transplanted tumor mouse model was constructed,and the expression level of apoptotic proteins in transplanted tumors was detected by Western blot.Label-free mass spectrometry proteomics and bioinformatics were used to analyze the differential proteins in gastric cancer cells before and after intervention;Western blot and qPCR experiments were used to detect the expression level of dif-ferential protein isocitrate dehydrogenase 1(IDH1),and ubiquitination experiments were used to detect the ubiquitination level of IDH1;kits were used to detect the levels of α-ketoglutarate(α-KG),NADPH/NADP+,glutathione(GSH/GSSG)and reactive oxy-gen species(ROS)content.RESULTS The anoikis rate of gastric cancer cells was reduced after TAM exosomes intervention(P<0.05,P<0.01),while it was significantly increased after TAM+JPYZ exosomes intervention(P<0.05,P<0.01).In the in vivo mouse experiment,the ratio of Cleaved Caspase-3/Caspase-3 in the tumor of the TAM exosome group was reduced(P<0.05),while the ra-tio was significantly increased after TAM+JPYZ exosome intervention(P<0.05).Proteomic analysis showed that IDH1 was significant-ly different after intervention,and was related to tricarboxylic acid cycle metabolism.Compared with the M0 group,the IDH1 ubiquiti-nation level of gastric cancer cells in the TAM group with exosome intervention was increased,the levels of α-KG,NADPH/NADP+and GSH/GSSG were significantly increased,and the ROS content was reduced(P<0.05),while TAM+JPYZ exosomes could reverse the above phenomenon.CONCLUSION JPYZ Formula can regulate TAM exosomes to cause ubiquitin degradation of IDH1 in gas-tric cancer cells,reduce the level of tricarboxylic acid cycle metabolism in gastric cancer cells,promote ROS accumulation,induce anoikis in gastric cancer,and thus inhibit the development of gastric cancer.

Objective To observe the manifestations of isolated bicuspid aortic valve(i-BAV)in children using echocardiography.Methods Echocardiographic data of 79 children with i-BAV were retrospectively analyzed,and classification of i-BAV was performed.The patients were divided into complication group(n=50)and non-complication group(n=29)according to the existence of valve and/or aortic involvement or not,and echocardiographic parameters were compared between groups.Results After adjusting body surface area(BSA),in complication group,left ventricular end-systolic diameter/BSA was lower,while left ventricular myocardial mass index group was higher than those in non-complication group(both P＜0.05).Type 0 i-BAV was found in 22 cases,with lat subtype as the most common ones(18/22,81.82％),while Type Ⅰ was observed in 57 cases with L-R subtype as the most common ones(39/57,68.42％).The most common subtype in complication group was also Type Ⅰ L-R(31/50,62.00％),with incidence of valve involvement of 90.00％(45/50),mainly including mild aortic stenosis and/or incompetence(37/45,82.22％),and incidence of aorta involvement of 24.00％(12/50),all with type Ⅰ or Ⅱ aortic widening.Conclusion The most common subtype of i-BAV in children was type Ⅰ L-R,with mild valve damage as the main complication and possibility of left ventricular myocardial remodeling.

Objective:To investigate the safety and efficacy of maribavir for the treatment of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed the clinical characteristics and outcomes of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allo-HSCT treated with maribavir at Hebei Yanda Lu Daopei Hospital from April 2024 to September 2024.Result:A total of 25 patients received maribavir, including 21 haploidentical transplants, two sibling HLA-matched transplants, and 2 HLA-matched unrelated transplants. Among them, 21, 2, and 2 patients received the first, second, and third transplants, respectively. The median time to the onset of CMV viremia and CMV disease was 120.5 (6-298) days post-transplantation. The median peak plasma CMV copy number was 6 400 copies/ml (range: 1 100-650 000 copies/ml). Six patients were diagnosed with CMV disease. Maribavir was administered after a median of 9.5 (1-41) days after CMV infection. The median duration of maribavir administration was 11.5 (6-43) days. Post-treatment, maribavir was effective in 25 (100%) patients. Two patients experienced grade 1 taste abnormalities, and one patient experienced grade 2 myelosuppression.Conclusion:The application of maribavir after allo-HSCT for treating refractory, drug-intolerant CMV viremia and CMV disease is safe and effective.

Objective:This study aimed to investigate the role of human herpesvirus (HHV) infection in refractory intestinal graft-versus-host disease (GI-GVHD) after hematopoietic stem cell transplantation (HSCT) and its diagnosis and treatment.Methods:This study retrospectively analyzed patients presenting with refractory GI-GVHD after allogeneic HSCT (allo-HSCT) with concomitant colonoscopy and mucosal biopsy at Lu Daopei Hospital, Yanda, Hebei, from March 2022 to July 2024. Human herpesvirus 6 (HHV6), HHV7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) detection with the RQ-PCR method. The intestinal mucosa was pathologically assessed and immunohistochemistry was utilized to detect the CMV early antigen, CMV late antigen, and EBV by in situ hybridization.Results:This study included 42 patients, consisting of 25 males and 17 females with a median age of 26 (1-59) years. All were histopathologically diagnosed as GI-GVHD. Among them, 34 (81.0%) cases had combined viral enteritis, with 52.4% positive for EBV, 38.1% positive for HHV6, 26.2% positive for CMV, and 14.3% positive for HHV7. Further, 17 (40.5%) cases had mixed viral infections, including 5 EBV+ HHV6, 3 CMV+HHV6, 3 CMV+EBV, 2 CMV+EBV+HHV6, 2 EBV+HHV6+HHV7, 1 EBV+HHV7, and 1 HHV6 + HHV7 cases. Furthermore, 17 (40.5%) had a single viral infection, including 9 EBV, 3 CMV, 3 HHV6, and 2 HHV7 cases. Moreover, 17 (40.5%) patients exhibited a positive histopathological viral test, including 7 (16.6%) CMV-positive and 12 (28.5%) EBV-positive cases. The same positive virus was detected in the feces of all 34 patients with positive tissue homogenate virus, and the positive rate of the same virus in the blood was 17.6%. Tissue homogenized virus testing was utilized as the diagnostic criterion for enterocolitis: blood tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity of 45.4%, 4.5%, 6.3%, and 0%, and specificity of 90.3%, 95%, 100%, and 110%, respectively. Additionally, fecal tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity and specificity of 100%. Treatment based on etiology caused ORR and CR rates for diarrhea of 76.1% (32/42) and 66.6% (28/42), respectively. The median follow-up of 42 patients was 13 (1 - 49) months, and 28 patients survived, with an expected 2-year survival rate of 61.9%.Conclusion:In addition to GVHD itself, intestinal human herpesvirus infection is one of the reasons for the refractory nature of GI-GVHD. Viral testing in blood and tissues reveals significant segregation, and the possibility of comorbid viral enteritis cannot be excluded even if a patient with GI-GVHD tests negative for blood viruses.

Objective:To investigate the safety and efficacy of maribavir for the treatment of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed the clinical characteristics and outcomes of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allo-HSCT treated with maribavir at Hebei Yanda Lu Daopei Hospital from April 2024 to September 2024.Result:A total of 25 patients received maribavir, including 21 haploidentical transplants, two sibling HLA-matched transplants, and 2 HLA-matched unrelated transplants. Among them, 21, 2, and 2 patients received the first, second, and third transplants, respectively. The median time to the onset of CMV viremia and CMV disease was 120.5 (6-298) days post-transplantation. The median peak plasma CMV copy number was 6 400 copies/ml (range: 1 100-650 000 copies/ml). Six patients were diagnosed with CMV disease. Maribavir was administered after a median of 9.5 (1-41) days after CMV infection. The median duration of maribavir administration was 11.5 (6-43) days. Post-treatment, maribavir was effective in 25 (100%) patients. Two patients experienced grade 1 taste abnormalities, and one patient experienced grade 2 myelosuppression.Conclusion:The application of maribavir after allo-HSCT for treating refractory, drug-intolerant CMV viremia and CMV disease is safe and effective.