Objective To investigate the antitumor activity of IL-24 delE5 in human leukemia cell line K562. Methods The expression of mda-7/IL-24 and its splice variant induced by TPA in leukemic cell lines, U937 and HL-60, was evaluated. The effects of IL-24 delE5 in K562 on cell proliferation, colony-forming ability, cell cycle, apoptosis, and tumor growth in vivo by using MTr assay, colony forming assay, flow cytometry, Annexin-V/PI and tumor xenograft models in nude mice were assessed. Meantime, the effects of IL-24 delE-5 and mda-7/IL-2A were compared. Results The expression of IL-24 dciE5 was detected in differentiated U937 and HL-60 cells. Transfection with IL-24 delE5 significantly reduced tumor cell viability, inhibited colony formation. Comparing with the control, G_0/G_1 stage add from (24.46±3.99) % to (42.69±3.04) %, caused cell cycle arrest in G_0/G_1 stage and significantly inhibited the growth of K562 transplantation tumor. No significant differences in the aforementioned antileukemia characteristics between IL-24 delE5 and mda-7/IL-24 was found. Conclusion Similar with mda-7/IL-24, IL-24 delE5 can efficiently inhibit the proliferation of K562 in vitro and in vivo, probably through induction of G_0/G_1 cell cycle arrest.

Objective To explore the mechanism of the cell-cycle arrest induced by human melanoma differentiation associated gene-7 (mda-7/IL-24) in chronic myelocytic leukemia cell line K562. Methods Microarray analysis was performed to determine the genes that were differentially regulated by mda-7/IL-24 in K562 cells, and was validated by realtime PCR. The phosphorylated pRb were detected by Western blotting analysis. Results A microarray analysis showed that G_0/G_1 phase-associated genes p21~(WAF-1) and BCCIP were up-egulated, while cdk6 and Smurf2 were down-regulated. The directional change in the expression of the four genes was successfully validated with real-time quantitative RT-PCR. pRb Set~(795) phosphorylation was observed with no modification of the pRb protein level. Conclusion These results suggest that IL-24/mda-7 may inhibit K562 proliferation and induce G_0/G_1 cell cycle angst by up-regulating p21~(WAF-1) and BCCIP, down-regulating cdk6 and Smurf2.

Objective: To explore the relationship among osteopontin(OPN), Interleukin-17A(IL-17A), anti-MBP auto-antibody and autism spectrum disorder(ASD), and to provide the theoretical basis for the etiology and pathogenesis of ASD. Methods: Forty autistic children and forty matched healthy children were enrolled in this case-control study. The levels of OPN, IL-17A, anti-MBP autoantibody in serum were measured by enzyme-linked immunosorbent assay (ELISA). The associations between those metabolic levels and the severity and intelligence of ASD children were performed by Pearson or Spearman correlation. Results: Children with ASD had higher serum levels of OPN, IL-17A [(296.89±162.95),0.93] pg/mL compared to healthy control[(217.98±113.39), 0.62] pg/mL(P<0.05). Serum OPN, IL-17A, and anti-MBP auto-antibody levels in ASD group were not correlated with the scores of ABC, CARS, and PPVT(P>0.05). However, anti-MBP auto-antibodies level in children with ASD were positively correlated with OPN and IL-17A levels, respectively(r=0.35, 0.34, P<0.05). Conclusion It was obvious that the ASD children were found with neuroimmunologic abnormality, and the underlying mechanism needs to be further explored.

Objective: To understand the status of doctor visit, rehabilitation and foster care of children with autism spectrum disorders in Heilongjiang Province, and to provide a scientific reference for improving ASD rehabitation education system and making the related policies. Methods: Eight autism rehabilitation institutions were selected in Heilongjiang Province by stratified cluster sampling, 357 primary caregivers of ASD children participated in the survey by using the questionnaire "ASD Children’s Rehabilitation Education Status and Needs". Results: The average age of abnormal behavior found of ASD children was (31.08±12.96)months, and the average age of first doctor visit was (35.88±13.20) months, the average age of diagnose was (38.64±13.20) months, and initial rehabilitation was (43.56±16.08)months. The proportion of children who had been diagnosed and have trained in the rehabilitation institutions before the age of 3 years was only 39.0% and 32.0%, respectively. The proportion of rehabilitation out of home town was 47.3%, and rehabilitation >20 hours per week was 73.4%. The proportion of fathers’ and mothers’ work lives affected was 34.5% and 67.8%, respectively, the differences were of statistical signficance(χ2=226.32, P<0.01). About 41.2% of ASD families received government financial support. Conclusion The average age of diagnose is late prolonged, and the proportion of children diagnosed and training before the age of 3 years was relatively low. There were obvious regional differences of rehabilitation education resources distributions of ASD in Heilongjiang Province. The results also demonstrate the need to sustain and enhance the coverage rate of the government financial support.

Objective: To investigate the level of human blood basic fibroblast growth factor (FGF2) among children with autism spectrum disorder (ASD) and its correlation with behavioral phenotypes, to provide a reference for etiological research of ASD. Methods: ASD Children were selected to get rehabitation training in reseach center of children development behavior in Harbin Medical University and the rehabitation constitution for ASD disabilities in Heilongjiang, 40 children were induded as ASD group, 41 healthy children in Harbin kindergarten was classified as control group. The Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Peabody Picture Vocabulary Test (PPVT) were used to assess the severity and intelligence of ASD children, respectively. Results: No difference was found in FGF2 level between ASD children (4.95 pg/mL) and normal children(8.51 pg/mL)（P>0.05). However, difference in FGF2 level between the two groups were found in 4-year-old group(P<0.05). The level of FGF2 differed across different severity and intelligence of ASD children(P<0.05). Conclusion Abnormal levels of FGF2 in ASD children may correlate with severity of autistic traits and intelligence of children.

Objective To evaluate the clinical efficacy of clear aligner for crowded dentition in early permanent teeth by moving the upper and lower molars far.Methods A total of 36 adolescent patients with Class Ⅰ Angle malocclusion admitted in our department from March 2017 to August 2023 were enrolled,and they were 17 males and 19 females,and at a mean age of 13.20±0.53 years.Clear aligner was applied to push the upper and lower molars backward to obtain a neat dentition.Lateral cephalometric X-ray film before and after treatment was measured,and paired t-test was used to compare the cephalometric measurements before and after treatment.Results The average course of treatment was 21.2 months.Overbite,overjet and molar relationship were turned to normal after treatment,and the soft tissue profile was maintained.Analysis of relevant cephalometric items showed that the Ptm-U6 distance was decreased by 2.89±1.22 mm,and the Go-L6 distance was decreased by 2.61±1.07 mm after treatment,with significant differences(P＜0.01).While,there were no statistically differences in UL-EP,LL-EP,NLA and FCA before and after treatment.Conclusion With reasonable treatment target and good tooth movement design,clear aligner can effectively move the upper and lower molar distally to correct moderate dentition congestion in early permanent teeth,and meanwhile the patients'profile is maintained.

Objective To describe the status of anxiety and depression in patients with uveitis, and to explore the related factors of quality of life. Methods A total of 126 uveitis patients from September 2015 to March 2016 were investigated with the General Social Population Questionnaire, Life Quality for Diseases with Visual Impairment Scale, Self-rating Anxiety Scale and Beck Depression Inventory. Results There were 126 valid questionnaires, and the effective recovery rate was 96.9％(126/130). The score of Self-rating Anxiety Scale in uveitis patients was (43.49±7.20) points which lower than the standard mark standardized score, and 14.3％ (18/126)of patients were diagnosed with anxiety. The score of Beck Depression Inventory in uveitis patients was (7.50 ± 6.60) points which lower than the standard mark standardized score, 28.6％ (36/126)of patients were diagnosed with depression. The Self-rating Anxiety Scale scores and psychological dimensions of quality of life was negatively correlated (r=-0.310, P<0.01), and the Beck Depression Inventory scores and the average score of the quality of life, the 4 dimensions and total score of quality of life was negatively correlated(r=-0.534--0.240, all P<0.01). The multiple linear regression analysis showed that the related factors of quality of life were score of depression, vision loss, education and gender(P<0.05). Conclusions The incidence of depression and anxiety are both lower in patients with uveitis than general population. The status of quality of life is related to the score of depression, vision loss, education and gender.

Objective:To investigate the correlation between systemic inflammatory response index (SIRI) and the outcomes at 90 d after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke received intravenous thrombolysis in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively enrolled. SIRI was calculated according to neutrophil count, lymphocyte count, and monocyte count at admission. The modified Rankin Scale score was used to evaluate the outcomes at 90 d after onset. 0-2 was defined as good outcome, and 3-6 were defined as poor outcome. Multivariate logistic regression analysis was used to evaluate the independent correlation between SIRI and poor outcomes. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI for poor outcomes. Results:A total of 303 patients with acute ischemic stroke receiving intravenous thrombolysis were enrolled in the study, including 178 (58.7%) males. Their median age was 69 years (interquartile range 60-78 years), and 69 patients (22.8%) had poor outcomes. SIRI in the poor outcome group was significantly higher than that in the good outcome group (1.53±2.45 vs. 3.51±4.73; P<0.05). Multivariate logistic regression analysis showed that the National Institutes of Health Stroke Scale (NIHSS) score at admission (odds ratio [ OR] 1.230, 95% confidence interval [ CI] 1.151-1.315; P<0.001) and SIRI ( OR 1.240, 95% CI 1.074-1.432; P=0.003) were significantly associated with the poor outcomes at 90 d. ROC curve analysis showed that the areas under the curve for SIRI and NIHSS scores alone and in combination to predict poor outcomes were 0.721 (95% CI 0.650-0.792; P<0.001), 0.824 (95% CI 0.771-0.878; P<0.001) and 0.853 (95% CI 0.804-0.902; P<0.001), respectively. The best cut-off values were 1.59, 8.00, and 0.23, respectively, and the sensitivity and specificity were 60.9% and 73.9%, 76.8% and 75.6%, 75.4% and 82.5%, respectively. Conclusions:High SIRI at admission is independently associated with 90-day poor outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. SIRI may be used as an outcome predictor in patients undergoing intravenous thrombolysis.

Objective:To analyze the diagnostic value of metabolic makers in cerebrospinal fluid in advanced lung adenocarcinoma patients with leptomeningeal metastases (LM) .Methods:A total of 46 cerebrospinal fluid samples (LM group) from lung adenocarcinoma patients with LM admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from December 2019 to December 2021 were collected, and 48 cerebrospinal fluid samples (control group) from patients with benign neurological diseases during the same period were collected. Metabolomics analysis of cerebrospinal fluid was carried out by high-performance liquid chromatography-mass spectrometry. Principle component analysis (PCA) and orthogonal to partial least squares discriminant analysis (OPLS-DA) were used for modeling. Multi-criteria assessment was used to identify the different metabolites between the two groups. Receiver operating characteristic (ROC) curve, pathway enrichment analysis and other methods were used to screen metabolites and pathways related to LM from lung adenocarcinoma.Results:There were no statistically significant differences in the proportions of age ( Z=-0.41, P=0.210) , gender ( χ2=1.19, P=0.275) , history of smoking ( χ2=2.86, P=0.091) , Karnofsky performance status score ( χ2=0.65, P=0.419) and increased intracranial pressure ( χ2=0.65, P=0.419) between the LM group and control group. The models of PCA (R2X was 0.608 and 0.583, Q2 was 0.462 and 0.513 in electrospray ion positive and negative modes, respectively) and OPLS-DA (R2Y was 0.967 and 0.889, Q2 was 0.959 and 0.852 in electrospray ion positive and negative modes, respectively) showed that the overall data quality was good. Meanwhile, the model interpretation rate and prediction rate were effective. The permutation tests duplicated for 200 times and showed no over-fitting of the established model. The metabolic profiles of the two groups were significantly different. A total of 30 endogenously differential metabolites were screened by using multi-criteria assessment. Six potential biomarkers with larger area under the curve (AUC) were identified through ROC curve analysis, including tyrosine (AUC=0.967, 95% CI: 0.906-1.000) , phenylalanine (AUC=0.992, 95% CI: 0.973-1.000) , pyruvate (AUC=0.976, 95% CI: 0.935-1.000) , tryptophan (AUC=0.935, 95% CI: 0.880-0.973) , glucose (AUC=0.932, 95% CI: 0.880-0.975) and adenosine monophosphate (AUC=0.993, 95% CI: 0.987-1.000) . The 30 selected differential metabolites were enriched and analyzed for metabolic pathways, and 20 relevant metabolic pathways were matched. Among them, the four metabolic pathways most likely to cause changes in metabolites were glycolysis and glucose metabolic synthesis, pyruvate metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Conclusion:Untargeted metabolomics analysis can effectively screen specific cerebrospinal fluid metabolites in lung adenocarcinoma patients with LM. Six potential metabolites such as tyrosine, phenylalanine, pyruvate, tryptophan, adenosine monophosphate, glucose and their metabolic pathways may be involved in the pathogenesis of LM from lung adenocarcinoma.

Objective To assess the clinical and cranial CT/MR features of leptomeningeal metastasis(LM)from lung adenocar-cinoma with non-enhanced T2-fluid attenuated inversion recovery(T2-FLAIR)hyperintensity on the brainstem surface.Methods Eleven cases with LM from lung adenocarcinoma with non-enhanced T2-FLAIR hyperintensity on the brainstem surface confirmed by cere-brospinal fluid cytology were analyzed retrospectively.The clinical features included the pathological classification of the primary tumor,genetic testing results,and treatment methods.The imaging features included lesion location,MRI(T1 and T2)signals,diffusion weighted imaging(DWI)signal,enhancement patterns,CT density characteristics.Results The features of non-enhanced T2-FLAIR hyperintensity on the brainstem surface of 11 cases among 98 patients(11.2％)with LM from lung adenocarcinoma were reviewed.All patients were lung adenocarcinomas with epidermal growth factor receptor(EGFR)gene mutation and were diagnosed with LM after receiving EGFR-tyrosine kinase inhibitors(EGFR-TKIs)targeted therapy.There were 5 cases located in the pons,2 cases in the midbrain and pons,and 4 cases involving the midbrain,pons and medulla oblongata with the symmetrical band-like high signal on non-enhanced T2-FLAIR imaging.On T1WI,1 case showed slightly high signal,10 cases showed equal signal.On DWI,4 cases showed high signal,7 cases showed equal signal,and on enhanced T1WI,1 case showed mild enhancement,and 10 cases showed no enhancement.Additionally,on cranial CT scans,1 case showed calcification on the brainstem.Conclusion Non-enhanced T2-FLAIR hyperintensity on the brainstem surface may be more common among LM patient from lung adenocarcinoma with EGFR gene muta-tions and TKIs treatment,with the most frequent site being the pons.The features may include non-enhanced T2-FLAIR high signal,non-enhancement on enhanced T1 WI,restricted diffusion on DWI,and calcifications on CT imaging.