Objective:To evaluate the effect of extracorporeal shock wave on the phosphoproteomics of the spinal cord in rats with diabetic neuralgia.Methods:Thirty-six healthy male SPF-grade Sprague-Dawley rats, aged 2 months, weighing 200-250 g, were divided into 3 groups ( n=12 each) using the random number table method: control group (group C), diabetic neuralgia group (group D), and extracorporeal shock wave + diabetic neuralgia group (group E). The rats were continuously fed a common diet in group C, while the rats were fed a high-sugar and high-fat diet for 8 weeks in D and E groups. Streptozotocin 35 mg/kg was intraperitoneally injected, and the successful induction of diabetic neuralgia was defined as the blood glucose >14.6 mmol/L and the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) ≤85% of baseline values. Group E received extracorporeal shock wave treatment after developing the model, with 1, 000 shocks per session at a frequency of 10 Hz and an energy of 1.0 bar, once per week for a total of 4 sessions. The MWT and TWL were measured before developing the model (T 0) and at 1, 2, 3 and 4 weeks after developing the model (T 1-T 4). After the last extracorporeal shock wave treatment, the rats were anesthetized and sacrificed, and lumbar spinal cord tissues were obtained for proteomic analysis and for detection of the expression of glial fibrillary acidic protein (GFAP), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) (by immunohistochemistry). Results:Compared with group C, the MWT and TWL were significantly decreased at T 1-T 4 in D and E groups ( P<0.05). Compared with group D, the MWT and TWL were significantly increased at T 1-T 4 in group E ( P<0.05). The results of phosphoproteomics screening revealed 284 differentially phosphorylated proteins in D and C groups, 282 in E and C groups, and 303 in E and D groups ( P<0.05). The results of immunohistochemistry showed that the expression of GFAP, IL-1β and TNF-α was significantly up-regulated in group D compared with group C ( P<0.05); the expression of GFAP, IL-1β and TNF-α was significantly down-regulated in group E compared with group D ( P<0.05). Conclusions:The mechanism by which extracorporeal shock wave alleviates diabetic neuralgia is related to inhibition of astrocyte activation and excessive phosphorylation of mGluR5 in rats.

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×10⁹/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×10⁹/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
Male ; Female ; Humans ; Child ; Retrospective Studies ; RUNX1 Translocation Partner 1 Protein/genetics* ; Core Binding Factor Alpha 2 Subunit/therapeutic use* ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Cytarabine/therapeutic use* ; Oncogene Proteins, Fusion/genetics* ; Chromosome Aberrations