Objective:To investigate the differences in gene mutations and functional clusters of gene mutations in patients with myelodysplastic syndromes (MDS) in the lower-risk and higher-risk groups.Methods:A retrospective case series study was conducted. Clinical data of 227 patients with MDS in Zhongda Hospital of Southeast University from January 2018 to August 2023 were retrospectively analyzed. According to the Revised International Prognostic Scoring System (IPSS-R), MDS patients were categorized into the lower-risk group (IPSS-R score ≤3.5 points, 96 cases) and the higher-risk group (IPSS-R score >3.5 points, 131 cases). Bone marrow specimens were tested for mutations of 58 common MDS genes using next-generation sequencing, and the 24 genes with the high mutation rates were included in the study, and the 24 mutated genes were categorized into 8 clusters according to gene function. The differences in clinical data, gene mutations and gene mutation functional clusters were compared between the lower-risk group and the higher-risk group.Results:At least 1 gene mutation was detected in 177 (78.0%) of 227 MDS patients, of which the 5 genes with high mutation rates were ASXL1 [21.6% (49/227)], TET2 [18.5% (42/227)], TP53 [15.4% (35/227)], DNMT3A [13.2% (30/227)], and U2AF1 [10.1% (23/227)] in turn. By gene function analysis, the most common mutation cluster was methylation-related genes [31.3% (71/227)], followed by spliceosome-related genes [24.7% (56/227)]. Platelet count and neutrophil count in the lower-risk group were higher than those in the higher-risk group, and the proportion of bone marrow primitive cells, the mutation rate and the presence of ≥3 mutations were lower than those in the higher-risk group (all P < 0.05). The 5 genes with high mutation rates in the lower-risk group were TET2 [21.9% (21/96)], DNMT3A [14.6% (14/96)], ASXL1 [13.5% (13/96)], SF3B1 [12.5% (12/96)], and U2AF1 [8.3% (8/96)] in turn. The 5 genes with high mutation rates in the higher-risk group were ASXL1 [27.5% (36/131)], TP53 [23.7% (31/131)], TET2 [16.0% (21/131)], DNMT3A [12.2% (16/131)], and U2AF1 [11.5% (15/131)] in turn, and the mutation rates of ASXL1, TP53, ETV6, and NRAS genes in the lower-risk group were lower than those in the higher-risk group (all P < 0.05). The mutation rate of methylation-related genes was the highest in both the lower-risk group and the higher-risk group, but the difference between the two groups was not statistically significant [32.3% (31/96) vs. 30.5% (40/131), χ2 = 0.08, P>0.05]. The differences in the proportions of tumor factor suppressor-related genes, transcription factor-related genes, chromatin-modification-related genes and RAS pathway-related genes mutations between the two groups were all statistically significant (all P < 0.05). Conclusions:The higher-risk group has a higher rate of common gene mutations and a greater number of gene mutations than the lower-risk group in MDS patients.

Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
Child ; Humans ; Autism Spectrum Disorder/metabolism* ; Proteomics ; Brain/metabolism*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-β1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-β/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.
Mice ; Animals ; Female ; Humans ; NF-kappa B/metabolism* ; Spike Glycoprotein, Coronavirus/pharmacology* ; Transforming Growth Factor beta1/metabolism* ; Angiotensin-Converting Enzyme 2/pharmacology* ; COVID-19 ; SARS-CoV-2/metabolism* ; Lung ; Antineoplastic Agents ; Transforming Growth Factor beta/pharmacology* ; Epithelial Cells/metabolism* ; Colon

Objective: To investigate the prevalence and factors influencing depressive symptoms among children with dyslexia in China. Methods: A total of 6 298 children in grades 3-5 were recruited from eight primary schools in Baoan, Shenzhen. The Questionnaire for Children s Reading Ability, the Dyslexia Checklist for Chinese Children, the Pupil Rating Scale Revised Screening for Learning Disabilities, and the Children s Depression Inventory short version were used. Results: The prevalence of dyslexia was 2.76%( n =174). The rate of depressive symptoms in children with dyslexia (37.36%) was higher than children without dyslexia (18.17%)( χ 2=40.94, P ＜0.01). Compared with children without dyslexia, children with dyslexia had an increased risk of depressive symptoms ( OR=2.65, 95%CI=1.87-3.75, P ＜0.01). In addition, the average time that a mother spent with her child every day was one of the factors influencing depressive symptoms. The risk of depressive symptoms was lower in children who spent ≥3 h with their mothers than children who spent <1 h(3-4 h: OR=0.54, 95%CI=0.36-0.81； 5-6 h: OR=0.51, 95%CI=0.34-0.78 ; ≥7 h: OR=0.47, 95%CI=0.32-0.69, P ＜0.01). Conclusion The rate of depressive symptoms in children with dyslexia was shown to be high. Increasing the time that mothers spend with their children every day is helpful in preventing the occurrence of depression in children.

Objective To understand the situation of cancer screening of community residents and its association with the knowledge of cancer core knowledge, and to provide reference for the formulation of secondary cancer prevention measures. Methods A cross-sectional survey was conducted among 2 037 residents aged 18-79 who lived in Bao 'an District, Shenzhen. Multivariate Logistic regression analysis was used to investigate the relationship between core knowledge and cancer screening behavior after adjusting for age, gender, education, marriage, occupation and smoking. Results The cancer screening rate of community residents was 28.10%, and the screening rate of middle-aged and elderly people aged 40-79 was 33.50 %.The proportion of ^“not very well understanding^”, ^“partial understanding^” and ^“basic understanding^” of the core knowledge of cancer were 43.91%, 42.33% and 13.76%, respectively, which was higher than that of the non-participants. Multivariate analysis showed that the women, the higher the level of education of college/university or above and the higher the level of knowledge of cancer prevention core knowledge, the higher the probability of participating in cancer screening was OR (95%CI ) : 2.40 (1.86-3.12), 1.65 (1.29-2.10), 1.38 (1.18 - 1.62), respectively. Conclusion The proportion of cancer screening in community residents needs to be improved, and the degree of core knowledge of cancer is closely related to cancer screening behavior. It is suggested to increase the publicity and education of the core knowledge of cancer, and at the same time, carry out the health education of secondary cancer prevention for the key population such as men and people with low education level, so as to improve the proportion of ^“early detection, early diagnosis and early treatment^” of cancer.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Objective: To analyze the possible responses of parents of young children to Child sexual assault (CSA) and the potential influencing factors, so as to provide evidence for prevention programs of CSA. Methods: Part of the data from "2016-2020 Child Injury Prevention Project" was used to analyze responses to CSA among parents of children younger than 3rd grade in primary school by chi square test and Logistic regression analysis. Results: A total of 4 072 parents were included in the analysis. Among them, 86.8% of parents chose "to solve problems together", 51.0% of parents taking children to a "psychologist", 4.9% of parents "scolding children for being too careless", 2.9% of parents "letting child not disclose abuse" and 6.5% of parents chose "other" coping methods. Parents with foreign nationality [OR(95%CI)=2.58(1.25-5.15)] and lower education level (OR=0.26-0.64) tend to "blame" their children. Mothers [(OR(95%CI)=0.54(0.33-0.90)], higher parental education level (OR=0.27-0.72) were more reluctant to encourage their children to keep quiet. Mothers [OR(95%CI)=1.73(1.32-2.27)], older children (OR=1.33-1.78) and parents with higher education level (OR=1.65-2.99) tend to "accompany". Parents aged 30 or more, and from high school/technical school/technical secondary school tend to take their children to see a "psychologist" [OR(95%CI)=1.39(1.14-1.71), 1.79(1.26-2.53)]. Conclusion Parents universally pay attention to the physical and mental health of children after CSA, but some parents still take negative coping methods, e.g. "blame" and "not disclose". Parenting educational level, duration of parent-child communication and age of children are primary factors associated with parental responses to child sexual assault. This study suggests that prevention secondary injury following child sexual assault should be farther strengthened, while fully considering the characteristics of the educated objects.

Oncogene StarD4 had the function of promoting proliferation and metastasis of triple-negative breast cancer (TNBC), but its clinical value and molecular mechanism are unknown. This paper found that StarD4 was highly expressed in cancer tissues of TNBC patients, and higher expression level of StarD4 in TNBC patient resulted in poorer prognosis. Based on transcriptomics of MDA-MB-231 cell model, the results of bioinformatics analysis showed that down-regulated expression level of StarD4 led to overall downregulation of cholesterol-relative genes and significant enrichment of cancer mechanism and pathway. Further analysis and investigation verified that StarD4 might cross-promote the protein stability of receptor ITGA5 through the cholesterol pathway to enhance TNBC progression, which provides guidance for clinical application of TNBC diagnosis and treatment.
Breast Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Lipids ; Membrane Transport Proteins ; Phosphoproteins

Objective:To preliminarily study the feasibility, safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with selective portal vein embolization (SPVE) before surgical resection in the treatment of large liver cancer.Methods:A retrospective study was conducted on the clinical data of 17 patients with large liver cancer treated with TACE combined with SPVE from January 2016 to December 2019 at the Department of Hepatobiliary Surgery, the Sixth Medical Center of PLA General Hospital. The study included 15 males and 2 females, aged (59.17±10.30) years. The levels of alanine aminotransferase, tumor changes and patient survival were analyzed before operation, after TACE, and after SPVE.Results:Among the 17 patients, the levels of alanine aminotransferase on the 1st and 3rd day after SPVE was significantly higher than those after TACE [191.4 (30.5-1966.4) IU/L vs 125.3 (35.7-846.2) IU/L on the first day, and 298.5 (24.6-1334.2) IU/L vs 208.6 (21.6-775.6) IU/L on the 3rd day], all P<0.05. One month after the two combined embolism, among the 6 patients with a tumor diameter of 5-10 cm, 2 patients (33.3%) had complete remission, 3 patients (50.0%) had partial remission, and 1 patients (16.6%) had stable disease. For the tumor’s longest diameter, among the 11 patients with tumors >10 cm, 1 patient had complete remission (9.1%), 4 patients had partial remission (36.4%), 5 patients had stable diseases (45.5%), and 1 patient had disease progression (9.1%). Eventually, 11 patients underwent surgical exploration. The median residual liver volume before treatment was 329.5 (284.9-365.7) ml, and after the combined procedure 415.6 (354.7-718.8) ml. The median hyperplasia ratio was 28.1% (14.1%-51.3%). Eight patients finally underwent surgical resection. There was no death in the perioperative periods. The median tumor-free survival time was 17 (7-42) months, and the median survival time was 27 (7-42) months. Conclusion:For patients with large liver cancer with insufficient remnant liver volume, preoperative TACE+ SPVE has certain value in controlling tumor progression, promoting remnant liver hyperplasia, increasing surgical resection rate and improving prognosis.