Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective:To investigate the role of stress-inducible protein Sestrin2 (Sesn2) in the improvement of insulin resistance in rat L6 skeletal muscle cells treated with liraglutide.Methods:The establishment of insulin resistance model of rat L6 skeletal muscle cells was induced by palmitate. The experimental cells were divided into control group(Con group), palmitate 0.6 mmol/L treatment group(PA group), palmitate 0.6 mmol/L+ liraglutide 10 nmol/L treatment group(PA+ Lir10 group), palmitate 0.6 mmol/L+ liraglutide 100 nmol/L treatment group(PA+ Lir100 group), and palmitate 0.6 mmol/L+ liraglutide 1 000 nmol/L treatment group(PA+ Lir1000 group). The cell counting kit 8(CCK8) method was used to detect the cell activity in each group. Western blotting was used to detect the expression levels of glucose transporter 4(GLUT4), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), and Sesn2 protein in L6 cells. L6 cells were transfected with siRNA to inhibit the expression of Sesn2. The cells were treated with palmitate and liraglutide. Western blotting was used to detect the expression levels of Sesn2, Akt, p-Akt, and GLUT4 protein in L6 cells.Results:Compared with Con group, the cell survival rate, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression in PA group decreased significantly( P<0.05). After liraglutide intervention, the cell activity, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression of PA+ Lir100 and PA+ Lir1000 groups was increased( P<0.05). After inhibiting the expression of Sesn2, p-Akt/Akt ratio and GLUT4 protein in transfected si-Sesn2 and treated with 0.6 mmol/L palmitate group(PA+ si-Sesn2 group) and transfected si-Sesn2 and treated with 0.6 mmol/L palmitate+ liraglutide 100 nmol/L group (Lir100+ PA+ si-Sesn2 group) were significantly lower than those in transfection negative group (si-Con group; P<0.05). Even after liraglutide intervention, compared with PA+ si-Sesn2 group, p-Akt/Akt ratio and GLUT4 protein expression level were not significantly increased in Lir100+ PA+ si-Sesn2 group ( P>0.05). Conclusions:Palmitate could induce the decrease of p-Akt/Akt ratio and GLUT4 protein expression in L6 cells. Liraglutide upregulates the expression of Sesn2, which leads to the increase of p-Akt/Akt ratio and GLUT4 protein expression and contributes to the improvement of insulin resistance.

Objective:To explore the current situation of rehabilitation resource and the influencing factors of rehabilitation nursing needs of patients at home in Xuzhou so as to provide a reference for home rehabilitation for patients.Methods:From October 2018 to December 2018, this study investigated all rehabilitation medical institutions (rehabilitation specialized hospitals, general hospitals with Rehabilitation Department, community health service institutions) in Xuzhou City by general investigation. Rehabilitation specialized hospitals in Xuzhou were investigated with the method of field visit and questionnaire survey, and the investigation content included the situation and professional categories of rehabilitation professionals. At the same time, totals of 411 patients with the needs for rehabilitation in Xuzhou were investigated, and the investigation content included the basic situation, rehabilitation needs of patients, contract service by family doctors. This study also analyzed the influencing factors of home rehabilitation nursing needs by Logistic regression.Results:There were 120 rehabilitation medical institutions in Xuzhou City. The bed number was 2 675 accounted for 57.98% (2 675/4 314) of the bed number shall be equipped with. There were 402 rehabilitation physicians, 432 rehabilitation nurses and 808 rehabilitation therapists respectively occupied 31.07% (402/1 294) , 16.69% (432/2 588) and 31.22% (808/2 588) of the planning. There were 30.90% (127/411) of rehabilitation patients signed a contract with community doctors, and 45.67% (58/127) of them dissatisfied with community doctors service and the satisfaction rate was 18.90% (24/127) . The influencing factors of family doctor contract included the ages of patients ( OR=0.557) , history of hemiplegia ( OR=1.520) and the number of community doctors ( OR=1.131) . The young the ages were, the better the contract degrees were. The factors promoted the contract were hemiplegia and increasing in the number community doctors. Conclusions:In Xuzhou, the rehabilitation medical resource allocation cannot meet the needs of the masses. The insufficient rehabilitation medical resource allocation reflected in the lack of rehabilitation talents, rehabilitation medical institutions and rehabilitation equipment. The rate of family doctors contract service was in the low level, and there are still great difficulties in the home rehabilitation.

Objective:To construct evaluation index system of traditional Chinese medicine (TCM) nursing quality of tuberculosis bases on "structure-process-result" three-dimensional quality structure model as a framework so as to provide evaluation standards and basis for tuberculosis TCM nursing quality management.Methods:By the convenient sampling method, 12 doctors and nurses in tuberculosis department from 2 third-class grade-A hospitals of Traditional Chinese medicine or integrated traditional Chinese and western medicine hospital in Zhejiang province were selected from March 2019 to April 2019 in order to conduct semi-structured interviews. 26 nursing experts were selected for expert consultation. Through literature research, semi-structured interview, Delphi method and superiority chart, the evaluation index system of TCM nursing quality of tuberculosis and the weight of each index were established.Results:The effective recovery rates of the letter questionnaires were 84.62% (22/26) and 77.27% (17/22) , the expert authority coefficients were respectively 0.831 and 0.843 and the Kendall's W were respectively 0.236 and 0.335. The eventually established evaluation index system of TCM nursing quality of tuberculosis included 3 first-level indicators, 16 second-level indicators and 56 third-level indicators. Conclusions:In this study, the evaluation index system of TCM nursing quality of tuberculosis constructed by various methods is more scientific, complete and reliable, which can provide references for the evaluation of TCM nursing quality of tuberculosis and the formulation of standard.

Objective To investigate the effect of intravenous ultrafine superparamagnetic iron oxide nanoparticles feraheme (generic name:ferumoxytol) on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion.Methods Thirty C57BL/6J mice were divided into sham operation group,saline control group,and feraheme group by the random number table (n =10 in each group).A permanent right middle cerebral artery occlusion model was induced by the modified suture method in the saline control group and the feraheme group,and no suture was inserted into the mice of the sham operation group.The intervention was performed by tail vein injection at 24 h after modeling.The sham operation group and the feraheme group were injected with 18 mg/kg feraheme,and the saline control group was injected with the same volume of normal saline.The neurobehavioral scores were conducted at 24 h (before the feraheme or saline injection) and 48 h (before the MRI exam) after modeling.MRI scans were performed at 48 h after modeling,and the cerebral infarction volume was calculated according to T2-weighted imaging.After the end of the scan,orbital blood was collected for the detection of serum tumor necrosis factor (TNF)-α,interleukin (IL)-1 β,and IL-6 levels.Then,the mice were sacrificed and the brain tissue was taken for HE staining and Ibal immunohistochemical staining.Results There were no significant differences in the infarct volume and neurological function score between the saline control group and the feraheme group.The serum levels of TNF-α,IL-1β,and IL-6 in the saline control group and the feraheme group were significantly higher than those in the sham operation group (P ＜0.05),but there was no significant difference between the saline control group and the feraheme group.Conclusion Intravenous injection of 18 mg/kg feraheme at 24 h after cerebral ischemia did not affect the infarct volume and inflammatory response,suggesting that this dose of feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

In order to improve the training quality of non anesthesiology professional physicians in anesthesiology department, the anesthesia department of Cancer Hospital affiliated to Harbin Medical Uni-versity Anesthesiology summed up the problems existing in the rotation process of anesthesiology depart-ment in the past, and explored the aesthesia teaching of the standardized doctors. We also improved the teachers' and students' awareness of the importance of anesthesiology learning, formulated standardized training programs, stimulated the interest of residents and teachers, strengthened teachers' teaching ability and teaching consciousness, Through the use of special lectures, case teaching, problem based teaching, we constructed diversified teaching to enhance the students' mastery of knowledge and skills in anesthesiology, and added purposeful examination at the end of rotation. As a result, the quality of anesthesiology rotation of non-anesthesia specialty residents was improved.

Objective To investigate the expression level of thymus microRNA-27a-3p in patients with myasthenia gravis (MG) and to explore the pathogenesis of MG.Methods Thymus tissue samples from 36 cases were collected from December 2014 to February 2015 in the Second Affiliated Hospital of Harbin Medical University.Nineteen thymus tissue samples of MG group were collected from department of chest surgery,17 thymus tissue samples of control group were collected from department of chest surgery or congenital heart disease patients from department of cardiac surgery.The expression of microRNA-27a-3p in the thymus from 36 patients was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR),using U6 as housekeeping control.The Wilcoxon Rank-Sum test was used to analyze the relative expression of microRNA-27a-3p of the two groups.Spearman rank correlation was used to determine the correlation coefficient between microRNA-27a-3p and Quantitative Myasthenia Gravis Score (QMGS).Results (1) The expression level of microRNA-27a-3p in thymus was significantly higher in MG group (0.195(0.049,0.714)) compared with control group (0.045(0.004,0.088),Z =-2.646,P =0.008).(2) Nineteen MG patients were included in the study,out of which 7 were ocular myasthenia gravis (OMG) patients and 12 were generalized myasthenia gravis (GMG) patients.The expression of microRNA-27a-3p in GMG patients (0.493 (0.157,1.123)) was significantly higher than that in OMG patients (0.035 (0.008,0.103),Z =-2.620,P =0.009).(3) There was a positive correlation between the expression of microRNA-27a-3p and QMGS (r =0.576,P =0.010).Conclusions The expression of microRNA-27a-3p in thymus is significantly up-regulated in the patients with MG.MicroRNA-27a-3p may be associated with MG severity and significantly elevated in GMG patients compared with OMG patients.

Objective To investigate the association between myasthenia gravis (MG) and single nucleotide polymorphisms (SNPs) of PTPN22 + 1858C/T,CTLA-4 (+ 49A/G;-1772C/T;-1661A/G),KRAS(rs9226),BCL2(rs4987855) and IGF-1R(rs34804698) genes.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was adopted to detect the gene types of SNPs in 76 MG patients who were enrolled in the Second Affiliated Hospital of Harbin Medical University from July 2011 to June 2015 and 59 healthy blood donors.Results In MG patients,the frequences of CTLA-4 +49A/G(rs231775) (57.9％) and-1772C/T (rs733618) (43.4％) were higher than that in the healthy controls (22.1％) (x2 =35.252,P =0.000; x2 =4.098,P =0.043).The frequence of CTLA-4 +49A/G in MG patients combined with thymoma (25.6％) was higher than other subgroups (thymic hyperplasia group:13.8％; normal thymus group:18.4％)(x2 =7.564,P=0.006; x2 =7.155,P=0.007).Meanwhile,the frequence of the C-1772 allele was higher in thymoma group (19.7％) compared with other two groups (thymic hyperplasia group:9.86％ ; normal thymus group:13.8％) (x2 =5.331,P =0.021 ;x2 =4.411,P =0.036).However,the other SNPs were not associated with the risk of MG.Conclusion There are associations of MG with CTLA-4 + 49A/G and-1772C/T SNPs,but not with PTPN,KRAS,BC12 and IGF-1R SNPs.

Objective To evaluate the diagnostic value of lung ultrasonography for transient tachypnea of new-born (TTN).Methods From January to December 201 4,a total of 1 358 children were hospitalized in the Neonatal Intensive Care Center and underwent lung ultrasonography at the Bayi Children′s Hospital,Beijing Military General Hospital.According to the patients′medical histories,clinical presentations,arterial blood gas analysis,chest X -ray examinations,and lung ultrasound examinations,there were 41 2 cases of patients without pulmonary lesions,228 cases of TTN,358 cases of respiratory distress syndrome (RDS),85 cases of meconium aspiration syndrome (MAS),21 5 ca-ses of infectious pneumonia,and 60 other cases at the time of hospital admission.In a resting state,the patients were placed in a supine,lateral recumbent or prone position.By using the anterior and posterior axillary lines as boundaries, the lung was divided into 3 regions:anterior,lateral,and posterior.The probe was perpendicular or parallel to the ribs, and each region of both sides of the lung was scanned.The scan results were compared to the conventional chest X -ray results.Results The main ultrasonic characteristics of TTN was pulmonary edema.In severe cases,the ultrasound showed a white lung or compact B -line.Compact B -line had 1 00.0% sensitivity and 95.3% specificity for diagno-sing severe TTN.Mild TTN presented as pulmonary interstitial syndrome or double lung point.Double lung point might appear during the recovery period of mild TTN or other diseases,such as RDS,MAS,and pneumonia,among others. Lung consolidation and air bronchogram were not observed in patients with TTN.Pleural effusion might occur in a varie-ty of lung diseases,and pleural line abnormality,A -line disappearance,and B -line or pulmonary interstitial syndrome were common ultrasonic manifestations of a variety of lung diseases.Conclusions Ultrasonic diagnosis of TTN,mainly based on pulmonary edema without lung consolidation and air bronchogram,is accuracy and reliable;however,double lung point is not a specific sign of TTN,whereas the identification of a white lung and compact B -line is a sensitive and specific sign of severe TTN.

Objective To investigate the clinical characteristics of aerophagia in children,and to evaluate the effect of 24 hours esophageal multichannel intraluminal impedance monitoring in diagnosis of aerophagia.Methods The clinical data of 30 children with aerophagia hospitalized in Department of Digestive Disease,Nanjing Children's Hospital Affiliated to Nanjing Medical University from July 2005 to June 2013 were reviewed.The 24 hours esophageal multichannel intraluminal impedance monitoring was performed in 8 cases of aerophagia.The treatment of these patients normally included psychological counseling,dietary adjustment,Iactulose,Domperidone and vitamins,while Simethicone was given to the patients if normal treatment was invalid.Results Of the 30 patients,aged 2 to 13 years,averaged (8.6 ± 4.5) years,the chief complaints were abdominal distention in 30 cases (100.00％),visible or audible air swallowing in 28 cases (93.33％),repetitive belching in 27 cases (90.00％),reduced appetite in 25 cases (83.33％),constipation in 22 cases (73.33％),psychological stresses in 15 cases (50.00％),recurrent abdominal pain syndrome in 10 cases(33.33％),chronic diarrhea in 3 cases(10.00％) and acute abdominal pain in 3 cases(10.00％).Among the 30 patients,24 hours esophageal multichannel intraluminal impedance monitoring was performed in 8 cases,averaging 149.63 (47-553)times of air swallowing were recorded.In the 30 patients,24 cases (80.00％) were relieved after being treated with psychological counseling,dietary adjustment,lactulose,domperidone and vitamins,and only 6 cases(20.00％) were invalid for normal treatment but well responeded to Simethicone.Conclusions Aerophagia is a kind of functional gastrointestinal disorders in children.Abdominal distention,air swallowing,repetitive belching,reduced appetite,constipation and pain are common symptoms.It can be cured through psychological counseling management,diet modification,laxatives,propulsives and vitamins.24 hours esophageal multichannel intraluminal impedance monitoring is a useful technology in the diagnosis of aerophagia children.