Combination of eriocalyxin B and homoharringtonine exerts synergistic anti-tumor effects against t(8;21) AML.

Understanding the molecular pathogenesis of acute myeloid leukemia (AML) with well-defined genomic abnormalities has facilitated the development of targeted therapeutics. Patients with t(8;21) AML frequently harbor a fusion gene RUNX1-RUNX1T1 and KIT mutations as "secondary hit", making the disease one of the ideal models for exploring targeted treatment options in AML. In this study we investigated the combination therapy of agents targeting RUNX1-RUNX1T1 and KIT in the treatment of t(8;21) AML with KIT mutations. We showed that the combination of eriocalyxin B (EriB) and homoharringtonine (HHT) exerted synergistic therapeutic effects by dual inhibition of RUNX1-RUNX1T1 and KIT proteins in Kasumi-1 and SKNO-1 cells in vitro. In Kasumi-1 cells, the combination of EriB and HHT could perturb the RUNX1-RUNX1T1-responsible transcriptional network by destabilizing RUNX1-RUNX1T1 transcription factor complex (AETFC), forcing RUNX1-RUNX1T1 leaving from the chromatin, triggering cell cycle arrest and apoptosis. Meanwhile, EriB combined with HHT activated JNK signaling, resulting in the eventual degradation of RUNX1-RUNX1T1 by caspase-3. In addition, HHT and EriB inhibited NF-κB pathway through blocking p65 nuclear translocation in two different manners, to synergistically interfere with the transcription of KIT. In mice co-expressing RUNX1-RUNX1T1 and KITN822K, co-administration of EriB and HHT significantly prolonged survival of the mice by targeting CD34+CD38- leukemic cells. The synergistic effects of the two drugs were also observed in bone marrow mononuclear cells (BMMCs) of t(8;21) AML patients. Collectively, this study reveals the synergistic mechanism of the combination regimen of EriB and HHT in t(8;21) AML, providing new insight into optimizing targeted treatment of AML.

Unilateral contrast-induced encephalopathy with contrast medium exudation: A case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare transient, reversible abnormality in the structure or function of the nervous system caused by the intravascular use of contrast agents. CIE can present with a range of neurological manifestations, including focal neurological deficits (hemiplegia, hemianopia, cortical blindness, aphasia, and parkinsonism) and systemic symptoms (confusion, seizures, and coma). However, if not accurately diagnosed and treated in a timely manner, CIE can cause irreversible damage to patients, especially critically ill patients. CASE SUMMARY: A male in his 50 s, 2 h after digital subtraction angiography, had a progressive disorder of consciousness, mixed aphasia, bilateral pupillary sluggish light reflex, and right limb weakness. Seven hours after the procedure, he developed unconsciousness, high fever (39.5 °C), seizures, hemiplegia, neck stiffness (+), and right Babinski signs (+). computed tomography (CT) findings 2 h postprocedure were very confusing and led us to misdiagnose the patient with subarachnoid hemorrhage. Brain CT was performed again 7 h after the procedure. Compared with the CT 2 h after the procedure, the CT 7 h after the procedure showed that the manifestations of subarachnoid hemorrhage in the left cerebral hemisphere had disappeared and were replaced by brain tissue swelling, and the cerebral sulci had disappeared. Combined with the clinical manifestations of the patient and after the exclusion of subarachnoid hemorrhage and cerebrovascular embolism, we diagnosed the patient with CIE, and intravenous fluids were given for adequate hydration, as well as mannitol, albumin dehydration, furosemide and the glucocorticoid methylprednisolone. After 17 d of active treatment, the patient was discharged with no sequelae. CONCLUSION: CIE should be taken seriously, but it is easily misdiagnosed, and once CIE is diagnosed, rapid, accurate diagnosis and treatment are critical steps. Whether a follow-up examination using a contrast agent can be performed should be closely evaluated, and the patient should be fully informed of the associated risks.

Surgical Revascularization of Symptomatic Kinking of the Internal Carotid Artery.

OBJECTIVE: To evaluate the safety and outcomes of surgical revascularization for patients with symptomatic kinking of the internal carotid artery (ICA). METHODS: Twenty-five consecutive patients presented with symptomatic kinking of the ICA and a history of transient ischemic attack (TIA) or stroke were prospectively enrolled in this study. All patients were treated with ICA transection and end-to-side reimplantation at the level of the carotid bulb. Patients were followed up for a median of 32 months. RESULTS: There were no deaths or strokes within the 30 days of the treatment. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. One (4%) patient had temporary recurrent nerve palsy, which was completely recovered at 4-week follow-up. One (4%) patient had a myocardial ischemic event. At the end of the 32-month follow-up, 1 (4%) patient developed ipsilateral minor stroke. No recurrent stenosis was detected by Doppler ultrasound. CONCLUSION: Surgical treatment for isolated, symptomatic kinking of the ICA and a history of TIA or stroke is safe, and the outcomes are acceptable.

Visual detection of glial cell line-derived neurotrophic factor based on a molecular translator and isothermal strand-displacement polymerization reaction.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF. METHODS: A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR) has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes. RESULTS: This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF. CONCLUSION: This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice.

Increased active von Willebrand factor during disease development in the aging diabetic patient population.

Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

[Reconstructive vascular operation for kinking of internal carotid artery].

OBJECTIVE: To evaluate and summarize the possibility and experience of reconstructive vascular operation for kinking of internal carotid artery. METHODS: Reconstructive vascular operation was performed on 5 patients with symptomatic kinking of internal carotid artery between July 2008 and June 2009. There were 2 male and 3 female patients, age ranged from 53 to 68 years (mean 62 years). Cutting the internal carotid artery at the bifurcation, mobilizing and stretching the internal carotid artery, then anastomosing the internal and common carotid artery. Two of them underwent endarterectomy simultaneously. RESULTS: For the 5 patients, postoperative recovery went smoothly and symptoms were well improved. Except that mild high perfusion syndrome happened in 1 patient, no other obvious complications. Kinking of internal carotid artery had been stretched in the postoperative CT angiography. In the 5-16-month follow-up, no transient ischemic attack or cerebral infarction happened, and no restenosis appeared. CONCLUSIONS: Reconstructive vascular operation is an effective surgical approach to kinking and coiling of the internal carotid artery. For some risk exists, all-round evaluation should be performed before operation, and operative indication should be strictly controlled.

Overweight and obesity-induced oxidative stress in children.

OBJECTIVE: To investigate whether overweight and obesity might cause oxidative stress and potential oxidative damage in overweight and obese children, and to explore its possible mechanism. METHODS: Eighty-five overweight and obese children (OOC), and eighty-five age-matched healthy children (HC) were recruited in this case-control study. The present study analyzed spectrophotometrically vitamin C (VC), vitamin E (VE), and 3-carotene (P-CAR) in plasma, as well as the activities of superoxide dismutase (SOD), catalase (CAT), and the level of malondialdehyde (MDA) in erythrocytes. RESULTS: Compared with those of VC, VE, P-CAR, SOD, CAT and MDA in the HC group, the average values of VC, VE, 3-CAR, SOD, and CAT in the OOC group were significantly decreased (P<0.001), while the average value of MDA in the OOC group was significantly increased (P<0.001). The regression analysis demonstrated that VC, VE, P-CAR, SOD, and CAT were negatively correlated (P<0.05-0.01), and MDA was positively correlated with BMI (P<0.05). Fitting to the model of multiple stepwise regression of BMI on VC, VE, P-CAR, SOD, CAT, and MDA in 85 OOC was Y= 27.0041 + 0.2541MDA - 2.1448beta-CAR - 0.0090CAT, where F= 43.8088, P<0.001, r = 0.7866, r(2)= 0.6187, adjusted r(2)= 0.6046. The findings from the reliability analysis for VC, VE, P-CAR, SOD, CAT, and MDA used to reflect increased oxidative stress and potential oxidative damage in the OOC showed that the reliability coefficients (alpha, 6 items) = 0.7231, P<0.0001, and that the standardized item alpha = 0.9207, P<0.0001. CONCLUSION: The present study suggests that there exists an increased oxidative stress in overweight and obese children.

[Multifactorial analysis of effects of mothers' autoimmune thyroid disease on their infants' intellectual development].

OBJECTIVE: To analyze factors relevant to retarded intellectual development in infants born to mothers with autoimmune disease of thyroid. METHODS: All the term newborns born to mothers with autoimmune thyroid disease (selection criteria) without asphyxia in all county, city, and provincial hospitals in Zhejiang province (except for Ningbo City) from July 2001 to June 2003 were enrolled through Zhejiang provincial neonatal disease screening network system. The control group was consisted of the neonates who were born to mothers without thyroid disease in these hospitals during the same period. Heel capillary blood samples were collected from the neonates older than 3 days in local hospitals and sent to the center of Zhejiang provincial neonatal disease screening network system. TSH levels were measured by Time Difference Fluorescent Analysis Device (1420 II type, EGG Company, US). If the level of TSH was higher than 9 mU/L, their mothers were called back to the center with their infants within 3 days. If the level of TSH was normal, they were called back to hospitals at age of 28 - 35 days of infants. The pattern of maternal thyroid disease, duration, thyroid function, the history of maternal drug administration, maternal age, gestational age and body weight of the neonates were recorded. The neonatal and maternal serum thyroid function tests were re-performed and the serum TPOAb, TGAb, TRAb and TSAb levels in both neonates and their mothers were measured as well. A 1-year follow-up study was done and all these subjects were investigated by means of Gesell development schedules by special investigators at the age of 1, 3, 6 and 12 months. The results were expressed as developmental quotient. Case-sectional study was performed. Statistical analyses were conducted using SPSS software. The multiple logistic regression analysis was used to analyze factors which might have effect on infantile personal-social ability, adaptive ability, gross motor ability or the fine-motor ability. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons and Dunnet's C test was used when variances were not equal. Correlation analysis was used to compare the anti-thyroid antibody between neonates and their mothers. RESULTS: Poor personal-social ability, adaptive ability, gross motor ability and fine motor ability of infants born to mothers with autoimmune thyroid diseases were found as compared to the infants born to healthy mothers (P < 0.01). Moreover, the infants born to mothers with Hashimoto's thyroiditis had significantly poorer fine motor ability and adaptive ability than those born to mothers with Grave's disease (P < 0.05). The Spearman correlation coefficients of TPOAb, TGAb, TRAb and TSAb were 0.636, 0.574, 0.619 and 0.473, respectively, and all the P values were lower than 0.01.The multifactor logistic regression analysis showed that infantile TPOAb levels and maternal TRAb levels were associated with infantile personal-social ability, adaptive ability, and gross motor; while maternal TPOAb levels and thyroid function during gestation were associated with infantile fine-motor ability (P < 0.05). CONCLUSION: Maternal autoimmune thyroid diseases during pregnancy had adverse effects on intellectual development of infants. The maternal levels of TPOAb, TRAb and thyroid status were associated with the infantile personal-social ability, adaptive ability, gross motor and fine motor development. In order to reduce the effect on infant, it is necessary to treat adequately the maternal autoimmune thyroid diseases during pregnancy.

Potential oxidative stress in children with chronic constipation.

AIM: To investigate the potential oxidative stress in children with chronic constipation and to explore its mechanisms. METHODS: Seventy children with chronic constipation and 70 age- and sex-matched healthy children were enrolled in a randomized controlled study. Plasma levels of vitamins C and E, activities of superoxide dismutase and catalase and lipoperoxide level in erythrocytes were determined by spectrophotometry. RESULTS: Compared with healthy children whose vitamin C, vitamin E, superoxide dismutase, catalase and lipoperoxide were 58.35+/-14.42 micromol/L, 27.15+/-6.55 micromol/L, 2 206+/-171 U/(g.Hb), 327.3+/-82.2 K/(g.Hb) and 19.18+/-4.27 nmol/(g.Hb) respectively, the levels of vitamin C, vitamin E, the activity of superoxide dismutase, and catalase in the children with chronic constipation significantly decreased [46.59+/-11.51 micromol/L, 20.65+/-4.80 micromol/L, 1943+/-147 U/(g.Hb) and 269.3+/-67.8 K/(g.Hb), respectively P<0.01], while the lipoperoxide significantly increased [25.22+/-5.01 nmol/(g.Hb), P<0.01]. With a prolonged course of disease, the levels of vitamin C, vitamin E, the activity of superoxide dismutase and catalase in the children with chronic constipation gradually decreased, while the level of lipoperoxide gradually increased. CONCLUSION: Chronic constipation can cause potential oxidative stress in children.

May chronic childhood constipation cause oxidative stress and potential free radical damage to children?

OBJECTIVE: To investigate whether chronic childhood constipation (CCC) may cause oxidative stress and potential free radical damage to children, and to explore the mechanisms by which CCC may cause oxidative stress and potential free radical damage to chronic constipation patients (CCPs). METHODS: Sixty CCPs and sixty healthy child volunteers (HCVs) whose ages, gender and others were matched for the CCPs were enrolled in a randomized controlled study, in which levels of vitamin C (VC) and vitamin E (VE) in plasma as well as activities of superoxide dismutase (SOD) and catalase (CAT) in erythrocytes were determined by spectrophotometric analytical methods. RESULTS: Compared with average values of the above biochemical parameters in the HCVs group, the average values of VC and VE in plasma as well as those of SOD and CAT in erythrocytes in the CCPs group were significantly decreased (P < 0.0001). Linear regression and bivariate correlation analysis showed that with prolonged course of the CCPs, the levels of VC and VE in plasma as well as the activities of SOD and CAT in erythrocytes in the CCPs were decreased gradually (P < 0.0001). CONCLUSION: The findings in the present study suggest that chronic childhood constipation causes oxidative stress and potential free radical damage to children with chronic constipation.

Influence of hypertension, lipometabolism disorders, obesity and other lifestyles on spontaneous intracerebral hemorrhage.

OBJECTIVE: To investigate whether hypertension, abnormal lipometabolism, obesity, cigarette smoking and alcohol drinking affect the intracerebral hemorrhagic volumes (IHV) in patients with spontaneous intracerebral hemorrhage (SIHP), and to explore the roles of these factors in spontaneous intracerebral hemorrhage (SIH). METHODS: Five hundred patients with acute SIH and 200 healthy adult volunteers (HAV) were enrolled in a study of independently randomized controlled design, in which the levels of systolic pressure (SP) and diastolic pressure (DP), and total cholesterol (TCH), triacylglycerols (triglycerides, TG), high density lipoprotein cholesterol (HDL-CH), low density lipoprotein cholesterol (LDL-CH) in serum as well as the level of erythrocytic membrane cholesterol (EM-CH) were measured, and the body mass index (BMI), daily cigarette smoking consumption (DCSC) and daily pure alcohol consumption (DPAC) were calculated. RESULTS: Compared with the average parameters in the HAV group, those of SP, DP, TG, LDL-CH and BMI in the SIHP group were significantly increased (P < 0.0001), while those of HDL-CH and EM-CH were significantly decreased (P < 0.0001). The linear regression and correlation analysis showed that with increased SP, DP, LDL-CH, BMI, DCSC, DPAC and aging as well as decreased HDL-CH and EM-CH, the IHV levels in SIHP were increased gradually (P < 0.0001-0.01). The linear stepwise regression analysis suggested that there existed a close correlation among the values of SP, DP, TCH, TG, HDL-CH, LDL-CH, EM-CH, BMI, DCSC, DPAC, age and IHV of the SIH patients, and that Y = -12.4583 + 0.1127SP -1.1977EM-CH + 0.9788LDL-CH + 0.2477BMI + 0.0382DCSC + 0.0248DP, P < 0.0001 approximately 0.05. CONCLUSIONS: The findings in the present study suggest that significantly increased systolic and diastolic pressure, low density lipoprotein cholesterol, body mass index and daily cigarette smoking consumption, and significantly decreased erythrocytic membrane cholesterol may be likely the main factors affecting intracerebral hemorrhagic volumes in patients with acute spontaneous intracerebral hemorrhage.

[Comparison study on child anxiety disorder with different family characteristics]

OBJECTIVE: To investigate the relations between child anxiety disorder with different family characte ristics. METHODS Family characteristics were measured by family environment scale. 144 mothers of child with anxiety disorder and 100 mothers of health children were invited to fill out questionnaires. RESULTS There were obviously different family characteristics between health children and those with anxiety disorder except phobic anxiety disorder. The scores of cohesion, independence, achievement orientation and active recreational orientation in children with anxiety disorder were significantly lower than those in health children P<0.01). In 4 groups of children with anxiety disorder cohesion showed correlation with intellectual- cultural orientation r=0.9219, 0.8348, 0.8935, 0.9550 respectively, P<0.001). CONCLUSION: The importance of family characteristics must be emphasized for children with anxiety disorder.