Objective To investigate the efficacy and safety of cladribine in the treatment of patients with refractory/relapsed acute myeloid leukemia (AML). Methods The data of 8 patients with refractory/relapsed AML treated with regimens containing cladribine at a dose of 5 mg/m2 per day for 5 consecutive days were retrospectively analyzed. The efficacy and adverse reactions were observed during treatment. Results Among the 8 patients, 5 patients achieved complete remission (CR), 1 patient achieved partial response (PR), and 2 patients obtained non remission (NR). The adverse reactions could be tolerated. Conclusion Regimen containing cladribine is an effective treatment procedure for the patients with refractory/relapsed AML, and its adverse reactions can be tolerated, which requires further clinical study.

Objective To propose a multi-scale convolutional neural network ( CNN) based lesions detection method of fundus image,and evaluate its application in diabetic retinopathy ( DR) assisted diagnosis. Methods A multi-scale CNN based on lesions detection method of fundus image was proposed. Compared with the existing detection methods,the problem of poor robustness based on threshold segmentation and morphological segmentation was overcome. The idea of multi-scale grids detection without relying on manual pixel-by-pixel labeling was adopted in this algorithm,and the detection performance of small lesions was significantly improved. In addition, multiple DR lesions with high accuracy could be detected by the proposed loss function under the condition of weak labels and small data sets. Results At the level of lesions,the sensitivity and specificity of hard exudation lesions detection were 92. 17％ and 97. 17％,respectively. Compared with single-scale method,the sensitivity and accuracy of multi-scale method proposed in this paper increased by 7. 41％ and 5. 02％,respectively,and compared with other algorithm using the same public dataset IDRiD, the specificity of this algorithm increased by 55. 82％. This method could effectively detect the lesions in fundus images,and could give the basic range of the lesions. The average detection time of fundus images with a large number of lesions was 1. 59 seconds. Conclusions The DR lesions in the fundus image can be quickly and reliably identified,the location information of the lesions can be marked,and the influence of subjective factors can be reduced by using this algorithm, and it can be used to assist the clinician to conduct more effectively.

Objective: To analyze the relationship between school bullying and parent child separation of left behind children, and to provide a theoretical basis for preventing and controlling school bullying of left behind children. Methods: A total of 4 945 children aged 7 to 18 in Shangrao City were selected by stratified cluster random sampling to complete the Chinese version of the School Bullying Experience Questionnaire(C-SBEQ), and the differences of school bullying between left behind and non left behind children were compared. The parent child separation data of 1 791 left behind children was obtained by self designed questionnaire, and the influence of parent child separation characteristics on school bullying of left behind children was analyzed by binary Logistic regression. Results: The rates of school bullying, bully victimization and perpetration of left behind children were 21.3%, 18.3% and 3.0% respectively, which were higher than those of non left behind children(15.4%, 12.7%, 2.7%). And there were statistical significance in the detection rates of school bullying among left behind children in different schooling stages( χ 2=9.82, P < 0.05), the detection rates ranked as follows:21.4% in primary school, 18.9% in junior high school and 14.7% in senior high school. The rate of bullying perpetration among left behind children was significantly higher in boys (4.8%) than in girls (1.0%)( χ 2= 14.69, P <0.05). The rate bully victimization among former left behind children (children with left behind experience) in the younger than 7 years group ( 20.3 %) was higher than that in the older than 7 years group(13.4%)( χ 2=4.79, P =0.03). There was no significant differences in the detection rate of bullying perpetration among the left behind children with different parent child separation experiences ( P >0.05). Control schooling stages, Logistic regression analysis showed that taking former school age left behind children as reference, bully victimization risk of former pre school left behind children was 1.64 times( OR=1.64, 95%CI= 1.04 -2.59, P <0.05). Conclusion School bullying of left behind children is more severce than that of non left behind children. Early occurrence of parent child separation is associated with higher risk of bullying victimization among left behind children.

Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To explore the characteristics of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients from Northeast China and their impact on prognosis. Methods:The clinical data of 252 CML patients and 49 Ph + ALL patients who were admitted to the First Hospital of Jilin University from January 2013 to October 2018 were retrospectively analyzed. The samples of bone marrow or peripheral blood were collected from patients when imatinib treatment was not effective. Nested polymerase chain reaction (PCR) was used to amplify the BCR-ABL1 kinase domain, and Sequencing Analysis v5.4 software was used to analyze the mutation of BCR-ABL1 kinase domain. Patients were followed up for 6-48 months, and the survival analysis was performed. Results:Among 252 CML patients, the mutations in ABL1 kinase domain were found in 57 patients (22.6%), including 25 patients in the chronic phase, 21 patients in the accelerated phase and 11 patients in the blast crisis; 50 patients had 20 types of single point mutation, and the most common mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the P-loop and C-helix domains; 7 patients had double mutations; patients with multiple mutations had the worst prognosis, with a median overall survival (OS) time of 3.2 months. Among 49 Ph + ALL patients, 17 cases (34.7%) were positive for mutations in the BCR-ABL1 kinase domain, 14 patients had 12 types of single point mutation, and 3 patients had multiple mutations; the median OS time of patients with multiple mutations, mutations located in the P-loop and C-helix domains and mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01). Conclusions:Among the imatinib-resistant CML and Ph + ALL patients from Northeast China, point mutations in the P-loop and C-helix domains are most commonly found. Multiple mutations, mutations in the P-loop and C-helix domains are related to the poor prognosis of the patients.

Objective:To delineate the morphological features of pedicle-facet joints in lumbar spondylolysis patients, correlating these with spinopelvic parameters to explore their mechanisms and clinical implications.Methods:This study enrolled 121 patients with L 5 spondylolysis (IS group), 108 with L 4, 5 degenerative spondylolisthesis (DS group), and 100 with normal L 4, 5 but L 5S 1 lumbar disc herniation (NL group), who underwent radiography and multislice spiral CT from May 2020 to January 2023. Parameters including vertebral slip percentage (SP) and spinopelvic alignments, such as sacral slope and lumbar lordosis, were quantified using standing lateral lumbar radiographs. Morphological parameters of the L 4 and L 5 facet joints were measured on 3D reconstructed lumbar CT images, including the facet joint angle (FJA), pedicle-facet joint angle (PFA), facet joint osteoarthritis (OA), and facet joint tropism (FT). Results:The analysis revealed significant variances in SS and LL among the groups ( F=21.910, P<0.001; F=22.439, P<0.001). The IS group exhibited the highest SS and LL, followed by the DS and NL groups. Morphological assessments showed the largest L 4 FJA in the IS group, with progressive decreases in the DS and NL groups ( F=344.791, P<0.001). Conversely, L 4 PFA was greatest in the DS group ( F=193.725, P<0.001). Notably, L 4 OA was markedly more severe in the DS group compared to IS and NL groups ( H=467.925, P<0.001), with no significant disparity between IS and NL groups ( P>0.05). Correlation analyses within each cohort highlighted a negative association of sacral slope and lumbar lordosis with facet joint angles, yet a positive correlation with pedicle-facet joint angles both with statistical significance ( P<0.05). Furthermore, L 4 facet joint angles were consistently smaller than those at L 5, and L 4 pedicle-facet joint angles were larger than L 5 ( P<0.05). Osteoarthritis at L 5 was more pronounced in the IS group compared to L 4 ( Z=7.043, P<0.001), a trend inversely observed in the DS group ( Z=11.868, P<0.001), while the NL group showed no significant osteoarthritic variance between levels ( Z=0.556, P=0.578). Conclusion:Patients with lumbar spondylolysis demonstrate elevated sacral slope and lumbar lordosis, indicative of increased localized biomechanical stress in the lumbar spine. These alterations in the morphology of the pedicle-facet joints highlight the distinctive structural adaptations and potential strain distributions within this cohort.

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

BACKGROUND:Hyperuricemia is a common metabolic disease,and the main clinical manifestation of patients with hyperuricemia is the formation of uric acid crystals leading to gout.Previous studies have only reported that uric acid crystals lead to intervertebral disc degeneration,but there are fewer studies on the correlation between hyperuricemia and intervertebral disc degeneration. OBJECTIVE:To retrospectively analyze the characteristics of intervertebral disc degeneration in patients with hyperuricemia and the correlation between serum uric acid level and intervertebral disc degeneration. METHODS:A retrospective analysis was performed in all patients diagnosed with intervertebral disc degeneration admitted at the Department of Orthopedics,the Affiliated Hospital of Southwest Medical University from January 2021 to December 2022.There were 97 hyperuricemia patients in the hyperuricemia group and 194 non-hyperuricemia patients in the control group according to sex and age in a ratio of 1:2.Blood uric acid test results were collected,and Pfirrmann scoring was performed for the degree of disc degeneration in patients based on the whole spinal MRI images.The difference in the degree of disc degeneration between the two groups was compared,and the correlation between the serum uric acid level and the degree of intervertebral disc degeneration was analyzed. RESULTS AND CONCLUSION:The Pfirrmann score in the hyperuricemia group was higher than that in the control group,and the total number of disc degeneration in the hyperuricemia group was also significantly higher than that in the control group(P<0.05).Spearman correlation analysis showed that the degree of disc degeneration in male patients was positively correlated with serum uric acid level at many spinal segments in the hyperuricemia group(C3/4:r=0.317,C4/5:r=0.333,C5/6:r=0.309,L2/3:r=0.443,P<0.05);the degree of disc degeneration in female patients was also positively correlated with serum uric acid level(C3/4:r=0.354,C4/5:r=0.388,C6/7:r=0.312,T7/8:r=0.282,T9/10:r=0.305,T11/12:r=0.277,L4/5:r=0.319,L5-S1:r=0.367,P<0.05).In the control group,there was no significant correlation between the degree of disc degeneration and serum uric acid level in male and female patients(P>0.05).To conclude,in patients with hyperuricemia,the higher serum uric acid level indicates the more serious intervertebral disc degeneration.Therefore,hyperuricemia is one of the risk factors for intervertebral disc degeneration.

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.