Objective To explore the role of cytokines on the pathogenesis of hypoxic-ischemic en-cephalopathy (HIE). Method The levels of peripheral blood interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) in 40 HIE and 40 healthy neonates were detected at the 1st, 3rd and 7th day after birth by using radioimmunoassay. Results Compared with healthy neonates, at the 1 st, 3rd after birth, the level of peripheral blood IL-6 was decreased [(52.3±24.5)ng/L vs (80.1±28.6)ng/L and (56.9±28.5) ng/L vs (78.6±28.9)ng/L, respoctively], but IL-15 and TNF-α were increased [IL-8:(0.68±0.23)ng/L vs (0.47±0.13)ng/L and (0.63±0.22)ng/L vs (0.40±0.16)ng/L, TNF-α: (1.17±0.30)ng/L vs (0.91± 0.30) ng/L and (1.14±0.29)ng/L vs (0.96±0.34)ng/L]in HIE infants. Conclusion The changes of plas-ma levels of IL-6, IL-8 and TNF-α in neonatal HIE possibly play an important role in the pathophysiologic mechanisms of HIE.

Objectives To validate the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) in hospitalized pediatric patients, and to assess the nutritional status and nutritional risk using STAMP. Methods the nutritional status of hospitalized pediatric patients was investigated by adopting STAMP. The STAMP score≥4 was deifned as a high standard of nutritional risk. Results Among 1 506 hospitalized children, children with high nutritional risk accounted for 26.56%. The overall prevalence of malnutrition and stunting was 19.12%and 10.16%, respectively. There was signiifcant diffe-rence in stunting among each department (P<0.05), which was the highest in department of internal pediatrics. The proportion of patients receiving nutritional support was 10.09%. Among them, the rate of parenteral and enteral nutrition support was 7.84%and 2.92%, respectively. The ratio of parenteral nutrition to enteral nutrition was 2.68:1. After intervention to hospitalized pa-tients with high nutritional risk, the overall prevalence of high nutritional risk decreased from 26.56%at admission to 21.71%at discharge (P<0.05). Conclusions STAMP can objectively relfect the possible malnutritional risk in hospitalized pediatric patients. The nutrition condition of the pediatric patients can be improved through nutritional risk management.

Objective To study the repair function of united endothelial progenitor cells (EPC)transplantation on injured liver endothelium by bone marrow transplantation (BMT) conditioning.Methods C57BL/6 mice were divided into four groups randomly: normal control group, without any treatment; irradiation alone group, administered a total body irradiation(TBI) pretreatment, without BMT; (3) BMT alone group: C57BL/6 mice were infused with bone marrow mononuclearcells (MNC) 5 × 106/only through caudal vein not more than 4 h after the same TBI pretreatment as the irradiation alone group; united transplantation group: receiving the same way as the BMT alone group, but C57BL/6 mice were infused with EPC 5 × 105/only at the same time. Two, 4, 7, 14, and 21 days after the TBI, the changes of the liver weight were observed regularly. The histopathological examination of liver was done at the 4th, 7th, 14th, and 21st day after the TBI. Results In irradiation alone group, BMT alone group and united transplantation group the liver weight began to increase significantly on the day 2 and peaked at 14th day after the TBI, and the peaks were respectively (1.65±0. 15) times (P＜0. 05), (1.61 ±0.06) times (P＜0.05), and (1.11 ±0.40)times (P＜0. 05) of those in normal control group. At the day 14, the liver weight in irradiation alone group, BMT alone group and united transplantation group began to decrease, and on the day 21 the liver weight in united transplantation group had been completely restored to normal level, however the liver weight in irradiation alone group and BMT alone group were still significantly heavier than that in normal control group (P＜0. 05). Liver histopathological examination revealed that there were obvious sinusoidal endothelial cells (SEC) injury, hepatocyte edema and severe inflammatory cell infiltration in irradiation alone group, and on the day 7 the hepatocyte edema and necrosis were significantly worse than before, and almost no alive SEC were found. On the day 14 the injury of SEC in BMT alone group was lighter than before, but on the day 21 the injury had not returned to normal. On the day 7 the injury of SEC, hepatocyte edema and necrosis were alleviated in united transplantation group as compared with irradiation alone group and BMT alone group, and on the day 14 the injury had returned to normal basically. Conclusion The transplantation conditioning could damage recipient liver endothelium and the injury would persist, and united EPC infusion could repair the injured SEC following BMT.

Objective To investigate the CD47 expression in de novo acute myelogenous leukemia (AML) patients with normal karyotype and its clinical significance. Methods One hundred thirty-seven cases of de novo AML with normal karyotype and 3 healthy volunteers were selected. Relative CD47 expressions in normal bone marrow hematopoietic stem cells (HSC) and multipotent progenitor (MPP) from healthy volunteers, as well as bone marrow mononuclear cells (MNC) and leukemia stem cells (LSC, Lin-CD34+CD38-CD90-) from AML patients were determined by flow cytometry. CD47 expression on the Lin-CD34+CD38-LSC-enriched fraction of specimen was determined by flow cytometry. The FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) was detected by using the Genome Analyzer platform. CD34+CD38-CD47hi and CD34+CD38-CD47lo expressing cells were identified and purified using FACS. Two groups of cells were inoculated with MethoCult H4445 medium on agarose-containing methylcellulose plates. After 12 days, MPP colony forming units (CFU) were counted, and 1×105 CD34+ CD38- CD47lo and CD34+ CD38-CD47hi cells were transplanted into NSG (NOD-SCID IL-2R γ null) mice irradiated by 280 cGy, and mice were sacrificed after 8 weeks. The ratio of human CD45+cells was detected by flow cytometry. Results The expression of CD47 in AML patients was higher than that in the healthy control. CD47 was expressed in all FAB (French-American-British) subtypes of AML. No significant difference in CD47 expression among different FAB subtypes was found (F=0.545, P>0.05). Among the 37 patients with CD34+CD38-CD47hi, 17 (46 %) were FLT3-ITD negative, and 20 (54 %) were FLT3-ITD positive. Among the 100 patients with CD34+CD38-CD47hi, 63 (63%) cases were FLT3-ITD negative, 37 (37%) cases were FLT3-ITD positive. The rate of FLT3-ITD positive in patients with CD34+ CD38- CD47lo had no statistical difference compared with patients with CD34+CD38-CD47hi (χ2= 3.79, P> 3.79). The CD34+CD38-CD47lo or CD34+CD38-CD47hi which was selected by FACS, was inoculated with the methylcellulose plate containing agarose for 12 days, and CD34+CD38-CD47lo cells could form CFU. The NSG mouse transplantation experiment showed that CD34+CD38-CD47lo cells could be reconstructed hematopoiesis, and CD34+CD38-CD47hi implantation failed. Conclusion CD34+CD38-CD47hi could enrich LSC, which may be a potential marker to detect minimal residual disease.

Objective:To analyze and explore the independent risk factors of 28-day mortality in patients with septic myocardial injury.Methods:A retrospective cohort study was conducted to collect clinical data of 505 patients diagnosed with sepsis related myocardial injury admitted to the intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from January 2015 to December 2020. According to the 28-day survival status of patients, they were divided into survival group and death group. COX multivariate regression analysis was used to analyze the influencing factors of the 28-day mortality rate of sepsis related myocardial injury patients, and receiver operating characteristic (ROC) curves were drawn to evaluate the effectiveness of independent risk factors in predicting the 28-day mortality rate of sepsis related myocardial injury patients.Results:A total of 505 patients with sepsis myocardial injury were included, of which 282 survived on 28 days and 223 died, with a mortality rate of 44.16%. COX multivariate regression analysis showed that Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate (LAC), oxygenation index (PaO 2/FiO 2), admission heart rate, and albumin were independent risk factors for sepsis associated myocardial injury mortality at 28 days (all P<0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of SOFA score was 0.766 2, and the 95% confidence interval (95% CI) was 0.724 5-0.807 9; The predictive value of 28-day mortality in sepsis associated myocardial injury patients was superior to APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin [The AUC values were 0.754 1(0.711 5-0.796 7), 0.752 6(0.710 1-0.795 1), 0.697 0(0.649 7-0.744 2), 0.623 2(0.573 7-0.672 7), and 0.620 3(0.570 8-0.669 7), respectively]. Conclusions:SOFA score, APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin are independent risk factors for the 28-day mortality rate of sepsis related myocardial injury. Clinical practice should identify these factors early, intervene early, and improve patient prognosis.

Objective:To develop and validate the accuracy of an independent dose calculation toolkit for the horizontal beamline of Shanghai Advanced Proton Therapy (SAPT) facility based on an open-source dose calculation engine.Methods:Machine data, such as absolute integral depth doses (IDDs) and lateral profiles in air were measured and lateral profiles in water were derived by Monte-Carlo simulations. The dose computation models for SAPT horizontal beamline pencil beams in water were achieved by combining machine data and dose calculation engine. The verification of the dose reconstruction toolkit included absolute dose verification and relative dose verification. The absolute dose verification is performed to mainly compare the reconstructed value and the measured value at different depths along the center axis of the beam direction of a cube plan. The relative dose verification is conducted to mainly compare the lateral profile or two-dimensional dose distribution between the measured value and the reconstructed value. Meanwhile, the precision of double-gaussian and single-gaussian lateral beam models was compared.Results:The deviations of the absolute dose between the calculated and measured values were basically within 2%. The deviations of 20%-80% penumbra between the measured and the calculated values were within 1 mm, and deviations of the full width at half height were within 2 mm. For 3 cube plans and 2 clinical cases, the two-dimensional gamma pass rates (3 mm/3%) between the measured and calculated dose distributions at the corresponding depths were greater than 95%. The double-gaussian lateral beam model was more accurate in the high dose gradient region and deeper depth.Conclusion:The precision of independent dose calculation toolkit is acceptable for clinical requirements, which can be employed to investigate other dose-related issues.

Objective:To investigate the clinical characteristics, efficacy and prognostic influencing factors of IgD multiple myeloma (MM) in the new immunotherapy era.Methods:The clinical data of 29 patients diagnosed with IgD MM in the Affiliated Hospital of Xuzhou Medical University from March 2014 to February 2021 were retrospectively collected. The clinical characteristics, treatment regimens and efficacy, especially the efficacy of new drugs and immunotherapy for the disease were analyzed. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional risk model was used for analysis of prognostic influencing factors.Results:The median age of patients was 58 years. There were 20 cases (69.0%) below 65 years, 12 cases (41.4%) of complicated with stomach function damage, 6 cases (20.7%) of extramedullary invasion. All patients were treated with combined therapy containing proteasome inhibitor bortezomib in the first-line therapy, and the overall response rate was 82.8% (24/29). Among 21 relapsed/refractory patients, 12 patients were treated with the second-line or above treatment regimen chimeric antigen receptor T cell (CAR-T) immunotherapy, including 9 cases achieving very good partial remission (VGPR) or above; 5 patients were treated with the new drug daratozumab, including 1 case achieving complete remission (CR). The median OS time of 29 patients was 48 months (95% CI 17-79 months), the median PFS time after the first-line treatment was 9 months (95% CI 3-15 months), and the median PFS time after the second-line treatment was 11 months (95% CI 1-21 months). Multivariate Cox regression results showed that CAR-T therapy is an independent influencing factor of the prognosis of relapsed/ refractory IgD MM patients ( HR = 0.094, 95% CI 0.019-0.473, P = 0.004). Conclusions:IgD MM patients are characterized with lower onset age, more renal function damage and a high incidence of extramedullary invasion. The first-line therapy containing proteasome inhibitor has a better short-term efficacy, and CAR-T therapy can improve the remission rate and survival rate of relapsed/refractory IgD MM to a certain extent.

Objective:To analyze the influence of magnetic field on the proton beam delivery and dose distribution, and develop a correction method for the Bragg peak (BP) shift under the vertical magnetic field, providing reference for the dose calculation and beam delivery of MRI-guided proton therapy.Methods:Monte Carlo (MC) simulation was used to study the dose distribution of the proton beam in the water phantom under the magnetic field. The BP location was corrected by the method of" angle correction+ energy correction" , and the correction parameters were calculated by the analytical formula based on the simulation data.Results:The magnetic field caused the dose distortion and shift of BP location. The shift degree was increased with the increase of field strength and initial energy. Compared with MC simulation, the result of calculating proton deflection in the air by the analytical method yielded a deviation within 0.2%. Based on the simulation data and calculation formulas, the correction parameters under different conditions could be calculated within 1 s by using the MATLAB programming. The calculation results showed that the air layer with magnetic field, isocenter depth, irradiation direction exerted different influence on the correction parameters. After correction, the BP location was basically consistent with the expected (offset ≤0.2 mm).Conclusions:The BP shift under the vertical magnetic field can be effectively corrected by " the angle correction+ energy correction" method. The correction parameters under different conditions can be quickly and accurately calculated by the calculation formulas based on simulation data.

OBJECTIVETo explore the expression and significance of miRNAs and Th17 related cytokines in patients with multiple myeloma (MM).

METHODSA total of 27 MM patients and 8 health controls were enrolled in this study. The expression of miR-15a/16,miR-34a,miR-194-2-192 cluster and miR-181a/b in bone marrow were detected by real-time quantitative PCR (qRT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of Th17 related cytokines interleukin-17 (IL-17), IL-21, IL-22, IL-23 and IL-27 in peripheral blood plasma. The role of miRNAs and Th17 related cytokines was analyzed in the development of MM.

RESULTSThe expression of miR-15a/16,miR-34a,miR-194-2-192 cluster in MM patients were significantly lower than those of the health controls, while miR-181a/b were exactly the reverse (P<0.05). The levels of IL-17, IL-21 and IL-27 were up-regulated in MM patients compared to health controls while IL-22 was down-regulated (P<0.05). There was no significant difference of IL-23 between the two groups. The levels of miRNAs and Th17 related cytokines had associated with ISS but not with some clinical parameters (such as gender, age, disease classification). Higher expression of IL-17, IL-21, IL-23, IL-27, miR-181a/b and lower expression of miR-15a/16,miR-34a,miR-194 and IL-22 were observed in the end stage than the early stage of MM patients (P<0.05). There was a significant correlation between miRNAs and Th17 related cytokines.

CONCLUSIONUp-regulated IL-17, IL-21 and IL-27 may potentially down-regulate the expression of several miRNAs in MM patients. Establishment of the relationship may be useful for understanding the pathogenesis of MM and for clinical diagnosis of the disease.

Cytokines ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Humans ; MicroRNAs ; Multiple Myeloma ; Real-Time Polymerase Chain Reaction ; Th17 Cells ; Up-Regulation