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 discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

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.

Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

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.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

Objective:To understand the dilemma of active management in young and middle-aged postoperative patients with lumbar disc herniation, in order to provide reference for the formulation of active intervention program of self-health management meeting the needs of patients.Methods:Using the phenomenological research method, a total of 16 middle-aged and young patients with lumbar disc herniation were selected for semi-structured in-depth interviews, and the themes were analyzed and extracted by Colaizzi 7-step analysis method.Results:Three themes and nine sub-themes were extracted namely, inadequate disease response capacity and response resources (lack of disease symptom management capacity, limited access to disease management information, difficult use of disease management information, difficulty in maintaining positive self-management for a long time (forced to stop behavior change due to stress, lack of motivation to achieve good behavior change, doubts about the effectiveness of self-management) and multi-dimensional negative emotions (contrast between maintaining independence and dependence on others, fear of being misunderstood, fear of relapse) .Conclusions:Medical staff should provide comprehensive health information services for young and middle-aged postoperative patients with lumbar disc herniation, improve the out-of-hospital follow-up mechanism with the help of information technology, further improve family and social support strategies, reduce the difficulties faced in the process of active management and achieve long-term active disease management.

Objective:To explore the range of medical reference value of thyroid hormone of pregnant women in early pregnancy in Jinan after adjustment of salt iodine content, so as to provide basis for clinical diagnosis and treatment of thyroid diseases of pregnant women in early pregnancy.Methods:A prospective study was conducted in 560 pregnant women in early pregnancy (0-13 weeks) who had underwent prenatal examination and thyroid function testing in Shandong Provincial Maternal and Child Health Care Hospital from January to December 2018. At the same time, 100 healthy non-pregnant women who were examined in the Health Examination Center of Shandong Provincial Maternal and Child Health Care Hospital were selected as the control population. Urine samples of pregnant women in early pregnancy were collected, and urinary iodine content was detected by arsenic cerium catalytic spectrophotometry. Venous blood samples were collected from pregnant women in early pregnancy and control population, the serum levels of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were detected by electrochemiluminescence (ECL), and the medical reference values of FT 3, FT 4 and TSH were established. Results:The median urinary iodine of pregnant women in early pregnancy was 162.21 μg/L, which was in the appropriate level of iodine. After the adjustment of salt iodine content, the medical reference values of FT 3, FT 4 and TSH in pregnant women in early pregnancy were 3.86-6.15 pmol/L, 12.56-22.16 pmol/L and 0.01-3.48 mU/ L, respectively; and the medical reference values of FT 3, FT 4 and TSH in control population were 3.55-6.05 pmol/L, 9.93-20.58 pmol/L and 0.54-5.92 mU/L, respectively. Conclusions:The iodine nutrition of pregnant women in early pregnancy in Jinan is appropriate after the adjustment of salt iodine content. The medical reference values of FT 3, FT 4 and TSH in pregnant women in early pregnancy are different from those in the healthy non-pregnant women. Therefore, it is of clinical significance to establish a medical reference value range of thyroid hormone for pregnant women in early pregnancy.

Objective: To explore the effect of PDCA nursing model combined with token reward on the compliance and negative emotions of children with hypospadias. Methods: A total of 120 children with hypospadias who were admitted to Children′s hospital affiliated to Zhengzhou University from February 2017 to December 2017 were selected as study subjects. According to the time of admission, they were divided into observation group and control group, with 60 cases in each group. The control group was given routine nursing care, the observation group was given PDCA nursing mode combined with token rewards intervention on the basis of routine care. The self-made children's behavioral compliance assessment table was used to compare the compliance of the two groups of children. Achenbach Child Behavior Check List (CBCL) scores were performed before and after the intervention. The hospitalization time and the incidence of complications were calculated. Results: There was no significant difference in CBCL scores between the two groups at admission (t=0.965, P=0.102). The scores of compliance and CBCL scores of the observation group were (43.12±3.99) points and (17.62±7.30) points respectively, the scores of control group were (30.67±4.53), (24.23±6.67), the difference was statistically significant (t=15.977, 5.184, P<0.01). The hospitalization time and complication rate of the observation group were (18.73±0.84)d, 15.00% (9/60), which were significantly lower than (20.92±1.90) d, 31.67% (19/60) of the control group, and the difference was statistically significant (t=8.166, χ²=4.658, P<0.01 or 0.05). Conclusions The PDCA nursing model combined with token reward can improve the compliance of children with hypospadias and improve their negative emotions.