Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Objective:To investigate the influencing factors of the survival in infants with congenital diaphragmatic hernia (CDH) and to develop a prediction model for CDH.Methods:Clinical data of 252 infants with a prenatal diagnosis of CDH in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2018 were retrospectively analyzed. Adverse outcomes were defined as neonatal death on discharge. Chi-square and t test were used for univariate analysis of 16 perinatal and five postnatal risk factors. Regression analysis was used to determine the independent predictors of survival. The receiver operating characteristics (ROC) curves of the risk factors for predicting the survival of CDH were drawn. A prediction model based on the combination of risk factors for predicting adverse outcomes of CDH was established using the cut-off value. ROC curves of the model were drawn and the area under curve (AUC), sensitivity, and specificity were calculated. Results:Out of the 252 patients, 173(68.7%) survived on discharge. Univariate analysis showed that lung-to-head ratio (LHR), polyhydramnios, right diaphragmatic hernia, liver herniation, intrathoracic stomach, premature birth, low birth weight, 5 min Apgar score <7, and amniotic fluid index (AFI) were significantly associated with the survival of CDH. Regression analysis showed that polyhydramnios ( OR=11.19,95% CI:2.83-45.33), liver herniation ( OR=2.81,95% CI:1.32-11.92), intrathoracic stomach ( OR=5.02, 95% CI:1.29-17.13), low birth weight ( OR=8.58,95% CI:1.59-45.01) and AFI ( OR=3.68, 95% CI:1.37-14.72) were independent risk factors for survival at discharge in children with CDH, while LHR ( OR=0.36, 95% CI:0.01-0.69) were protective factors. The predictive cut-off values of LHR, polyhydramnios, liver herniation, intrathoracic stomach, low birth weight, and AFI were 1.6, 1.0, 1.0, 1.0, 1.0, and 232.5 mm, respectively. The model based on the combination of the above indicators for predicting CDH adverse outcomes was shown with an AUC value of 0.904, predictive sensitivity of 0.747, and specificity of 0.896. Conclusions:In this study, LHR, liver herniation, intrathoracic stomach, polyhydramnios, low birth weight, and AFI are independent risk factors for CDH survival. The combination of prenatal and postnatal indicators is noted for a higher accuracy for predicting CDH survival.

Objective To investigate the diagnosis and prognosis of patients with coronary artery aneurysm in Kawasaki disease.Methods The data of ultrasonic diagnosis and follow-up of 338 children with Kawasaki disease complicated with coronary artery aneurysms were analyzed.Results The incidence of coronary artery aneurysm in the acute stage of Kawasaki disease was 21.2％ (338/1 594).Of all the 338 cases,small aneurysms was 66.6％ (225 cases),medium aneurysms was 25.1％ (85 cases),and giant aneurysms was 8.3％ (28 cases).There were 719 branches involved in 338 cases,32.8％ of them in left main coronary artery and 31.1％ in right coronary artery;25.3％ in left anterior descending branch,and 10.8％ in left circumflex branch.A total of 382 branches were followed up,including 218 branches of small coronary aneurysm group and 82.1％ of them were completely recovered to the normal diameter.The medium aneurysm group was 124 brunches,the proportion of no significant change,retraction,and normal were 23.4％,68.5％ and 8.1％,respectively.There were 40 brunches in the giant anuerysm group,in which the proportion of no significant change,retraction,and normal were 70.0％,27.5％ and 2.5％,respectively.A total of 30 thrombosiswere detected by echocardiography in the acute stage,20 thrombosis were regularly followed up,12 thrombosis gradually subsided,and the other remained persist.Five thrombosis were detected in the sequelae stage,and all located in the giant coronary aneurysm.Seven children were clinically diagnosed with ischemic heart disease,of them,acute myocardial infarction in 1 case,1 died of heart failure.Conclusions Kawasaki disease coronary artery disease are common in small coronary aneurysms,of which the left main artery and right coronary artery lesions are the most common,and the prognosis is better;medium and giant aneurysm need more time to recovery,and are easy to complicated with thrombosis.

Objective To investigate the value of echocardiography application in the diagnosis of large amount of pericardial effusion (PE) in children by retrospective etiology and prognostic analysis.Methods A total of 68 children with large amount of PE admitted in Beijing Children's Hospital,Capital Medical University from March 2010 to March 2016 were reviewed retrospectively,and the echocardiographic presentations,etiology diagnosis,treatment,and prognosis were analyzed.Results Analysis indicated that the etiology diagnosis ratio was 97.1％ (66/68 cases),the effective ratio of the medical treatment was 71.8％ (46/64 cases),and the mortality rate was 7.8％ (5/64 cases).The morbidity was ranked from high to low as follow:large amount of PE included infectious pericarditis 27 cases,tumor associated PE 14 cases,postpericardiotomy syndrome and cardiotrauma 14 cases,systemic diseases 6 cases,vasa lymphatic related diseases 5 cases and idiopathic PE 2 cases.PE resulted from tumor associated PE and vasa lymphatic diseases had lower cure rate than the overall cure rate,and there were statistical significance (28.6％ vs.71.8％,x2 =9.092,P =0.003;20.0％ vs.71.8％,x2 =5.059,P =0.018).Thirty-five children received pericardiocentesis or fenestration drainage.Chylopericardium was restricted to vasa lymphatic diseases.All tumor associated PE had the hemorrhagic PE.The strong echo point in the pericardial cavity might indicate implication for hemorrhagic PE (x2 =5.166,P =0.023).The abnormal mass detected by echocardiography might indicate the tumor related or infectious causes.Conclusions The etiology of large amount of PE could be determined in most of children.As the preferred diagnosis method,echocardiography could help etiological diagnosis combined with clinical manifestation.

Objective To investigate the characteristics of transperineal pelvic ultrasounds among middlelate gestational women and study the the correlation between middle-late gestation and stress urinary incontinence.Methods Seventy-four pregnant women at a gestation of 14-40 weeks were divided into the incontinence group (n =34) and the non-incontinence group (n =40).The bladder neck angle,the bladder neck rotation angle,the bladder neck movement degrees,the posterior urethra-vesical angle,and the urethral rotation angle at both inactivity and maximum Valslva activity were evaluated by pelvic ultrasound.The acquired data were treated and analyzed with t-test and correlation analysis with with P ＜ 0.05 considered statistically significant.Results Compared with the non-incontinence group,the bladder neck rotation angle,BND,bladder neck angle and posterior urethra-vesical angle during the maximum Valsalva activity in the incontinence group were all significantly larger (P ＜ 0.05).A moderate correlation between urethral rotation angle and gestation week in the incontinence was observed (P ＜ 0.05).Conclusion The changes of the supportive structures around bladder urethreal tissues in middle-late gestation women are obvious.The urethral rotation angle becomes larger with the gestation going on.

Objective To summarize the echocardiographic findings and clinical characteristics of Kawasaki disease(KD) complicated with coronary artery thrombosis (CAT).Methods Thirty-five patients with KD combined with CAT were enrolled,who were admitted to Beijing Children's Hospital,Capital Medical University between July 2005 and August 2016.The clinical characteristics and echocardiographic findings during follow-ups were retrospectively studied.According to whether the childrenhad been complicated with myocardial ischemia,the patients were divided into 2 groups:ischemic group and non-ischemic group.The duration of fever,the time when the intravenous immunoglobulin(IVIG) was first injected,the time when coronary artery aneurysms (CAA) was formed,the maximum diameter of CAA and inflammatory index inthe acute phase were compared between 2 groups.Results All of the 35 children diagnosed as KD combined with CAT suffered firom CAA,and the coronary thrombosis was detected in all the cases with aneurysms.Thirty-five patients had 99 branches of CAA,of which the maximum diameter of CAA was (9.6 ± 3.1) mm(4.0-19.0 mm).Fifty-four plots of CAT were detected in the aneurysms.The diameter of CAA that thrombosis located was larger than that of which the thrombosis was not located[(10.9 ± 2.8) mm vs.(7.9 ± 2.6) mm],and the difference was significant(P ＜0.01).During 4 months to 10 years and 8 months [(39.2 ±29.5) months] follow-ups,CAA regressed in 32 branches [32.3％ (32/99 branches)],of which 4 branches [4.0％ (4/99 branches)] completely regressed to the normal diameter.The maximum diameter of CAA regressed was smaller than the maximum diameter of CAA consistence [(7.3 ± 1.9) mm vs.(10.6 ± 3.0) mm],and the difference was significant (P ＜ 0.01).Out of 35 patients,15 cases [42.9％ (15/35 cases) had myocardial ischemia,while the other 20 cases[57.2％ (20/35 cases)] didn't have.Among 15 cases with myocardial ischemia,6 cases[17.1％ (6/35 cases)] had myocardial infarction,4 cases [11.4％ (4/35 cases)] had heart failure,and 1 case[2.9％ (1/35 cases)] died of acute heart failure complicated with severe ventricular arrhythmia.Compared with non-ischemic group,the children in the ischemic group had longer duration of fever[(19.1 ± 7.8) d vs.(12.1 ± 3.3) d],higher white blood cell account in the acute phase[(24.8 ± 13.5) × 1012/L vs.(19.7 ±4.0) × 1012/L],later treatment of IVIG [(13.9 ± 5.5) d vs.(9.8 ±3.8) d],and earlier CAA formation [(16.0 ±4.9) d vs.(20.9 ± 14.5) d],and the differences were statistically significant (all P ＜ 0.05).Conclusions CAT of children with KD commonly originates from CAA.Patients who have more serious inflammatory reaction in the acute phase,earlier formation,heavy severity and longer consistence of CAA are prone to have myocardial ischemia.Echocardiographic study plays an important role in monitoring CAA,detecting the CAT and finding the early left ventricle dysfunction,which is of clinical significance.

Objective To explore the influence of extended nursing care on postoperative quality of life (QOL) of patients undergoing coronary artery bypass grafting (CABG).Methods By convenience sampling method,86 inpatients with coronary heart disease (CHD),receiving CABG from January 2009 to July 2015 in department of cardiothoracic surgery of Yancheng Hospital Affiliated to School of Medicine,Southeast University,were selected and divided into the control group (n=43) and the experimental group (n=43) according to random number table method. Patients in the control group were cared by routine nursing,and were instructed at discharge about precautions,time of medicine taking and re-examination;while patients in the experimental group were cared by extended nursing according to previously designed health-management plan. Scores of QOL at discharge,one month after discharge and three months after discharge,incidence of abnormal blood pressure,blood glucose and blood lipid of patients between two groups were compared.Results There was no significant difference in the scores of QOL,incidence of abnormal blood pressure,blood glucose and blood lipid of patients between two groups at discharge and 1 month after discharge (P>0.05). Three months after discharge,scores of QOL of patients in the experimental group were significantly higher than those in the control group,while incidence of abnormal blood pressure,blood glucose and blood lipid is lower in the experimental group than those in the control group (P<0.05).Conclusions Extended nursing care for patients after CABG can stimulate their initiative in participating in self health management,and improve their QOL,which make it worth promoting.

To investigate the effects of 2-(4-methoxycarbonyl-2-tetradecyloxyphenyl)carbamoylbenzoic acid (CX09040) on protecting pancreatic β cells, the β cell dysfunction model mice were induced by injection of alloxan into the caudal vein of ICR mice, and were treated with compound CX09040. Liraglutide was used as the positive control drug. The amount and the size of islets observed in pathological sections were calculated to evaluate the β cell mass; the glucose stimulated insulin secretion (GSIS) test was applied to estimate the β cell secretary function; the oral glucose tolerance test (OGTT) was taken to observe the glucose metabolism in mice; the expressions of protein in pancreas were detected by Western blotting. The effects on the target protein tyrosine phosphatase 1B (PTP1B) were assessed by the PTP1B activities of both recombinant protein and the intracellular enzyme, and by the PTP1B expression in the pancreas of mice, separately. As the results, with the treatment of CX09040 in alloxan-induced β cell dysfunction mice, the islet amount (P<0.05) and size (P<0.05) increased significantly, the changes of serum insulin in GSIS (P<0.01) and the values of acute insulin response (AIR, P<0.01) were enhanced, compared to those in model group; the impaired glucose tolerance was also ameliorated by CX09040 with the decrease of the values of area under curve (AUC, P<0.01). The activation of the signaling pathways related to β cell proliferation was enhanced by increasing the levels of p-Akt/Akt (P<0.01), p-FoxO1/FoxOl (P<0.001) and PDX-1 (P<0.01). The effects of CX09040 on PTP1B were observed by inhibiting the recombinant hPTP1B activity with IC50 value of 2.78x 10(-7) mol.L-1, reducing the intracellular PTP1B activity of 72.8% (P<0.001), suppressing the PTP1B expression (P<0.001) and up-regulating p-IRβ/IRβ (P<0.01) in pancreas of the β cell dysfunction mice, separately. In conclusion, compound CX09040 showed significant protection effects against the dysfunction of β cell of mice by enlarging the pancreatic β cell mass and increasing the glucose-induced insulin secretion; its major mechanism may be the inhibition on target PTP1B and the succedent up-regulation of β cell proliferation.

Objective:To establish cell lines stably expressing Rab5a and its the inactive mutant Rab5aN133I,analyze the effect of Rab5a on the expression of cytokines in LPS-stimulated RAW264.7 cells .Methods:RAW264.7 cells were transfected with Rab5a and its inactive mutant vector Rab5a N133I separately,and then screened by G418.Rab5a stable expressing cell lines were identified by Real time-PCR.The growth of the stable cell lines was analyzed by MTT assay.After the stable cell lines were stimulated by LPS for different time periods,the expression of iNOS,TNF-αand IL-6 was detected.Results:Rab5a and Rab5aN133I transfection resulted in elevated Rab5a mRNA expression compared with the control cells ( P<0.05 ).Rab5a overexpression enhanced the proliferation of RAW264.7 cells.However,the proliferation of Rab5aN133I cells was significantly slower than the control cells ( P<0.05).Overexpression of Rab5a promoted LPS-induced production of iNOS,TNF-αand IL-6 in RAW264.7 cells (P<0.01). Conversely,overexpression of Rab5aN133I abolished the stimulating effects of Rab5a.Conclusion: Rab5a promoted LPS-induced expression of iNOS,TNF-αand IL-6 in RAW264.7 macrophages in a GTP-binding ability-dependent manner.