AIM: To study effects of urokinase-type plasminogen activator (uPA) signal transduction on expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) in giant cell tumor of bone (GCT). METHODS: Expression of uPAR, MMP-2 and TIMP-3 in GCT tissue was detected by immunohistochemistry. Phosphorylation level of mitogen-activated protein kinase (p44) in uPA/uPAR signal pathway in cultured GCT cells was detected by immunoprecipitation. The expression of MMP-2 and TIMP-3 in cultured cells after treatment with uPA-ATF or anti-uPAR antibody was also detected by Western blotting. RESULTS: 1) Urokinase-type plasminogen activator receptor (uPAR) was positive on the cell membrane and in cytoplasm of some mononuclear stromal cells (MSCs) and multinucleated giant cells (MGCs); 2) MMP-2 was positive in the cytoplasm and on the cell membrane of almost all of MSCs and some of MGCs. The polar distribution of MMP-2 in the cytoplasm of MGCs was especially obvious; 3) The expression of TIMP-3 of some MSCs and MGCs in GCT was much lower than MMP-2. The positive signal also showed a prominent polarity; 4) After treatment with uPA-ATF, the phosphorylation level of p44 in GCT cultured cells was much higher than the control. Addition of anti-uPAR antibody in the cells remarkably down-regulated the phosphorylation level of p44 as compared with the control group, suggesting that uPA-ATF participates cell signal transduction and this reaction can be inhibited by anti-uPAR antibody; 5) uPA-ATF cell signal pathway up-regulated expression of MMP-2 and TIMP-3, while anti-uPAR antibody down-regulated the expression of MMP-2 and TIMP-3. CONCLUSION: These results demonstrate for the first time that uPA-ATF directly regulates the expression of MMP-2 and TIMP-3 by signal transduction pathway, and the over-expression of MMP-2 and TIMP-3 may play an important role in local osteolysis of GCT. [

OBJECTIVE To explore the mechanism of methylamphetamine (MA) on heart toxicity. METHODS The effects of MA on delayed rectifier potassium current (IK) and action potential (AP) were analyzed in isolated decreased AP from 121.6 to 106.0 mV and delayed the action potential duration (APD), but had no effect on the resting potential. The 10%, 25%, 50%, 75% and 90% of APD (APD10, APD25, APD50, APD75 and APD90)inhibited the membrane potential of rapidly activating delayed rectifier potassium current (IKr) and slowly activating delayed rectifier potassium current (IKs), downward shifted the Ⅰ -Ⅴ curve, but had no effect on the curve shape and could be partly recovered after flushing. The tail current IKr was blocked concentration-dependently after simiarly inhibited by MA. CONCLUSION MA has inhibitory effects on Ik and AP in ventricular myocytes,which may be one of the possible electrophysiological mechanisms of the cardiac damage caused by MA.

OBJECTIVE: To explore the molecular basis for a pedigree affected with coagulation factor V (FV) deficiency. METHODS: Clinical data of the patient and his family members was analyzed. Targeted capture and next-generation sequencing (NGS) and Sanger sequencing were carried out to detect potential variant of the FV gene. RESULTS: The patient presented with jaundice and prolonged prothrombin time (PT) and activated partial thromboplastic time (APTT). V factor activity measured only 0.1% of the normal level, though the patient had no sign of bleeding. A paternal heterozygous variant c.653T>C (p.F218S) and a maternal heterozygous variant c.3642_3643del (p.P1215Rfs*175) were identified in the FV gene of the patient. His elder brother was a heterozygous carrier of the c.653T>C (p.F218S) variant. c.653T>C(p.F218S) was a known pathogenic variant, while the c.3642_3643del (p.P1215Rfs*175) variant was unreported previously. CONCLUSION Mutations of the FV gene probably underlie the hereditary coagulation factor V deficiency in this patient. NGS combined with Sanger sequencing has detected potential variant with efficiency and provided a reliable basis for clinical and prenatal diagnosis for this family.
Aged ; Factor V ; Factor V Deficiency ; genetics ; Genetic Variation ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Phenotype

Objective To investigate six-minute walk distancc (6MWD) of inpatients underwent cardiac surgery before discharge and to identify its influencing factors,and to provide references for further studies of hospital rehabilitation.Methods Using convenience sampling,from August 2016 to June 2017,167 eligible patients underwent cardiac surgery were recruited from a cardiovascular hospital in Beijing.General and disease-related intormation were collected.According to requirements of six-minute walk tcst (6MWT) from American Thoracic Society,patients' rehabilitation was evaluated using 6MWD.Results After discharge from intensive care unit(ICU),6MWD of patients increased along with hospital stays.On the day before discharge,mean 6MWD of patients was (213.86±75.87).The influencing factors of 6MWD included types of surgery (P=0.019),cardiopulmonary bypass (P=0.004),postoperative left ventdcular ejection fraction (LVEF)(P=0.015),and hospital stays after discharge from ICU (P=0.003).Conclusion During hospitalization,6MWD of patients underwent cardiac surgery increased along with hospital stays.On the day before discharge,6MWD of patients tended to be stable,and ready for further rehabilitation process.Patients could have different rehabilitation differences in types of surgery,using cardiopulmonary bypass,LVEF and hospital stays after discharge from ICU.

Learning objective clarity is very important for college students' classroom learning . Health assessment course as one of the compulsory course of nursing teaching, is the basis of nursing students' learn nursing profession, therefore to explore the related factors of health assessment course learning objec-tives has its practical significance. Under the guidance of the concept of the reform of the teaching system, the SIMPP analysis of the students learning objective in the college nursing students in health assessment course has been carried out. Results show that among college nursing students, three kinds of students' learning goals are very clear, four kinds of students' learning goals are clear, and two kinds of students' learning goals are unclear. The related factors influencing the nursing students' learning goal mainly are the student personal subjective factors. Teachers should pay attention to the observation of the students' study status in health assessment course, understand the student individual situation, control the clear degree of learning goals among students and do the ideological work of students at the beginning of the course to im-prove the students' clear degree of learning goals.

Objective:To summarize the clinical characteristics of neonatal cerebral infarction and its risk factors, so as to provide a reference for clinical diagnosis and early prevention of the disease.Methods:This study retrospectively analyzed the demographic data, clinical manifestations and brain imaging features of neonates with cerebral infarction ( n=45) admitted to the Department of Neonatal Critical Care Medicine of the Affiliated Children's Hospital of Xi'an Jiaotong University from June 2012 to July 2020. Ninety newborns without cerebrovascular disease matched for date of birth and gestational age were selected as the control. Two independent sample t-test, rank-sum test, Chi-square or corrected Chi-square test were used for univariate analysis and binary logistic regression were applied for analyzing the risk factors for neonatal cerebral infarction. Results:A total of 45 infants with clinically diagnosed neonatal cerebral infarction were enrolled, including eight small for gestational age and three macrosomia infants. The median age at disease onset was 1 d (1-2 d). There were 71% (32/45) presenting with convulsions as the first symptom, 4% (2/45) admitted with apnea and respiratory distress as the chief complaints, respectively,11% (5/45) having poor response and 9% (4/45) showing no obvious clinical manifestations. Cranial MRI and magnetic resonance angiography identified left hemisphere lesion in 25 cases (56%), right hemisphere lesion in 16 (36%) and both in four (9%). Thalamus and basal ganglia were involved in 11 cases. The lesions were supplied by middle cerebral artery [38% (17/45)], anterior cerebral artery ( n=1), posterior cerebral artery ( n=4), anterior and middle cerebral arteries ( n=4), middle and posterior cerebral arteries ( n=16), or anterior, middle and posterior cerebral arteries ( n=3). Univariate analysis showed that the proportions of small for gestational age [18% (8/45) vs 6% (5/90), χ 2=5.15], cesarean section after failure of trial of labor [18% (8/45) vs 1% (1/90), χ 2=10.85], meconium stained amniotic fluid [33% (15/45) vs 9% (8/90), χ 2=12.68], fetal distress [20% (9/45) vs 3% (3/90), χ 2=8.34] and neonatal asphyxia [16% (7/45) vs 2% (2/90), χ 2=6.56] were all higher in the infarcted infants than those in the control (all P<0.05). Binary logistic regression analysis revealed that small for gestational age ( OR=3.981, 95% CI: 1.075-14.742, P=0.039), cesarean section after failure of trial of labor ( OR=17.959, 95% CI: 2.032-158.698, P=0.009) and fetal distress ( OR=5.756, 95% CI: 1.129-29.331, P=0.035) were independent risk factors for neonatal cerebral infarction. Conclusions:Most neonates with cerebral infarction would have convulsions initially, while some are asymptomatic. Middle cerebral arteries are often involved in the lesion. The risk of this disease may be increased in small for gestational age infants, cesarean section after failure of trial of labor and fetal distressed cases.

Pulmonary hypertension(PH)is commonly seen in preterm infants with bronchopulmonary dysplasia(BPD)and is significantly associated with increased mortality.The pathophysiological basis of PH is pulmonary vascular dysplasia or remodeling, and airways hyperresponsiveness.At present, management of BPD-PH should be comprehensive supportive therapy and focus on targeted pharmacotherapies, including various pulmonary vasodilators with different vasoactive mechanisms, such as phosphodiesterase inhibitors, endothelin receptor antagonists and prostaglandins analogs.However, although expert consensus recommends targeted pulmonary arterial hypertension therapy, high-quality clinical studies on the safety and efficacy of these drugs are few.Pulmonary vascular remodeling inhibitors and stem cell therapy have enormous potential to reduce pulmonary hypertension and further research and more data are needed.