Cell-cycle deregulation leading to excessive cellproliferation is an important mechanism of human tumorigenesis. CDK6 and CDK4 have been found to be significant regulators of cellcycle, particularly in promoting cell -cycle progress. Moreover, these proteins are usually overly active in most tumors and closely related to tumor development. Recently, research has confirmed CDK4/6 as prospective targets for cancer therapy. However, the mechanism of excessive CDK6 activation leading to tumorigenesis is not completely understood. Therefore, further understanding of the role of CDK4/6 in cell -cycle regulatory pathways and celldifferenti-ation is essential, as well as their overexpression in different types of tumors. This information will elucidate the mechanisms of tumor development and treatment. Therefore, this review intends to discuss the structure and biological function of CDK6, the role and mecha-nism of CDK6 in carcinogenesis, and the clinical application of CDK6 inhibitors.

Background and purpose:Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is one of the ASPP family. It binds to p53 to inhibit the transcriptional activity of p53-target genes and cell apoptosis, which is asso-ciated with tumor formation. Previously, we found a new subtype of iASPP, iASPP splice variant (iASPP-SV), which is a nuclear protein containing 407 amino acid residues and can bind to p53, inhibiting p53 transcriptional activity. However, the relationship of iASPP-SV and breast cancer is still obscure. Therefore, the purpose of this research was to study the role of iASPP-SV on breast cancer tumorigenesis and progression.Methods:5’-rapid ampliifcation of cDNA ends (RACE) was used to identify the 5’-end of iASPP-SV mRNA in MCF-7 cells. HEK 293 cells were transfected with pFLAG-iASPP-SV and pFLAG-iASPP (828). Then Western blot was used to identify whether endogenous iASPP-SV was expressed in HEK 293 cells and 8 types of human tumor cell lines. This study established the stable clones of NIH 3T3 expressing FLAG-iASPP-SV and FLAG-iASPP (828). Cell proliferation assay, colony formation and soft agar colony formation assay were used to identify whether iASPP-SV and iASPP (828) can promote cell proliferation and iASPP-SV is an oncogene. Real-time lfuorescent quantitative polymerase chain reactive (RTFQ-PCR) was used to de-tect the levels of iASPP-SV and iASPP (828) mRNA in primary breast cancers. Luciferase assays were used to identify the relationships between iASPP-SV, iASPP (828), p53 and NF-κB p65.Results:The study identiifed that iASPP-SV was encoded by previously reported NF-κB p65 subunit (RelA)-associated inhibitor (RAI), and endogenously expressed in many human cancer cell lines. Analysis of cell proliferation, colony formation assay and soft agar assay for colony formation identiifed that similarly to iASPP (828), iASPP-SV promoted tumor cell proliferation and acted as an onco-gene. RTFQ-PCR result showed that the median values of iASPP-SV and iASPP (828) in breast cancers with wild-type p53 were more signiifcantly over-expressed than those of mutant p53. Luciferase assays showed that iASPP-SV and iASPP (828) could suppress NF-κB p65 transcriptional activity. Thus iASPP family may participate in the regulation of p53 and NF-κB activity, which imply that iASPP perhaps shows pro- or anti-survival activities when it interacts with different proteins.Conclusion:These ifndings indicate that iASPP-SV may be a potential target for breast cancer thera-py.

Objective To investigate the risk factors for coronary artery lesions (CALs) in children with Kawasaki disease (KD) in Lanzhou. Methods One hundred and seventy-four children with diagnosed KD were divided into CAL group and non-CAL group based on the existence of concurrent CALs. The age, gender, fever duration, intravenous immunoglobulin (IVIG) start time, IVIG dose, C-reactive protein (CRP), serum albumin, erythrocyte sedimentation rate (ESR), platelet (PLT), red blood cell count (RBC), hemoglobin and so on were compared. Results Among the 174 children, 46 children (26.44%) were complicated by CALs and 128 children were not. The differences of average fever duration, IVIG starting time, IVIG dose, PLT, CRP, ESR and RBC were statistically signiifcant (P<0.05). Conclusions When KD children has the fever durations>10 d, start of IVIG af-ter 10 days of fever, increase of PLT, CRP and ESR and decrease of RBC, clinicians should be alert to the risk of concurrent CAL.

ObjectiveTo explore the changes of astrocytes in vitro on the expression of Cyclin D1 under normal and hypoxia/reoxygenation conditions.MethodsThe primary astrocytes were isolated from the cortex of SD fetal rats(less than 24 hours) and identified by immunosytochemical method with anti-GFAP antibody after 3 passages.Astrocytes of passage 3 were divided into normal group ( control group),hypoxia/reoxygenation group ( H/R 37℃ ),and mild hypothermiaintervention group( H/R 32℃ )separately.Astrocytes from the later tow groups were reoxygenated with 4,12,and 20 hours separately after exposed to hypoxia conditions for 8 hours.Trypan blue staining was employed to detect the survival rates and immunofluorescence,western-blot were used to analyse the expressin of Cyclin D1 of of astrocytes of different groups and time points.Results 1.The GFAP positive astrocytes from passage 3 exceeded 95 ％.2.With regard to morphology and survival rates,there is no difference between astrocytes of normal and hypothermia groups after 8 hours exposure to hypoxia conditions.Reoxygenation could obviously rise astrocytes mortality with time went by ( H/R 37 ℃ group:12.87 ± 2.76 ( R4 ),31.55 ± 3.00 ( R12 ),46.40 ±8.50(R20) ;H/R 32℃ group:6.77 ± 1.53( R4),15.97 ±4.00(R12),28.33 ±5.69(R20) ;all P＜0.05).3.Immunofluorescence and western-blot revealed that reoxygenation increased Cyclin D1expression markedly,which was proportional to the duration of reoxygenation.Mild hypothermia could reduce Cyclin D1 expression of astrocytes severely under reoxygenation condition.ConclusionCyclin D1 expression can be regarded as a sensitive index of damage to astrocytes caused by hypoxia/reoxygenation conditions.

Objective Sarcopenia and metabolic syndrome share similar pathophysiological mechanisms. The aim of this study was to investigate the prevalence of sarcopenia among health examination population, and to analyze the relationship between sar-copenia and blood pressure, blood glucose, uric acid and lipids. Methods Physical examination data of 1191 healthy persons in the medical examination center of the hospital from Mar 2011 to Jun 2011 were collected. The weight, skeletal muscle, body fat, body mass index ( BMI) , waist circumference,body fat percentage, waist-hip ratio and visceral fat area were analyzed by human body compositionanalyzer and the prevalence of sarcopenia was observed. At the same time, triglyceride (TG), total cholesterol (TC), high density lipo-protein-cholesterol ( HDL-C ) , low density lipoprotein-cholesterol ( LDL-C) , uric acid and fasting blood glucose were also detected. Results The prevalence rate of sarcopenia of the subjects was 5.21%, and the highest incidence was found in ≥60 years group( 11.11%) . The prevalence rates of overweight and obesity were 33.8% and 10.2%, respectively. The prevalence of sarcopenia is grad-ually higher along with increasing BMI. The prevalence rates of sarcopenia of overweight and obesity subjects were 5.47% and 26.23%, respectively. Compared with the normal control group, the level of weight[(66.34±11.75)kg vs (76.71±12.84)kg ], BMI[(23.37± 3.13) vs (28.05±3.66)], body fat percentage[(25.33±6.06)% vs (36.76±4.47)%], waist circumference[(83.19±9.56)cm vs (95.45±13.74)cm] and visceral fat area[(88.96±29.74)cm2 vs (136.91±25.56)cm2] were higher in the sarcopenia group (P<0.05). Compared with the normal control group, the incidence of systolic blood pressure[(125.59±30.04)mmHg vs (139.39±19.79) mmHg], diastolic blood pressure[(75.82±11.95)mmHg vs (82.34±10.96)mmHg ] TG[(1.56±1.12)mmol/L vs (1.98±1.72)mmol/L] and uric acid[(313.75±83.07)mmol/L vs (335.55±96.07)mmol/L] were higher in the sarcopenia group (P<0.05). Compared with the normal subjects, the detectable rates of abnormal diastolic blood pressure, fasting blood glucose, uric acid, and LDL-C were increased in the sarcopenia, obesity and sarcopenia combined with obesity subjects (P<0.05). The odds ratio of abnormal systolic blood pressure, diastolic blood pressure, uric acid, and LDL-C increased in the sarcopenia, obesity and sarcopenia combined with obe-sity subjects using logistic regression analyses after correction of gender and age. Conclusion The sarcopenia may have some con-nection with metabolic risk factors. Early detection of sarcopenia can help to distinguish people predisposed to metabolic syndrome, and it has important significance for prevention of chronic disease.

Objective:To investigate the relationship between orthostatic intolerance (OI) and body mass index (BMI), blood lipid and serum protein levels in children and adolescents.Methods:A total of 122 children and adolescents aged from 6 to 17 years old, who were diagnosed with OI at the Department of Pediatric Cardiology, the Second Hospital of Lanzhou University from April 2018 to April 2019, were selected as the subjects.While, 56 children and adolescents in the health management center were selected as the healthy control group during the same period.Subjects were divided into syncope group and non-syncope group according to whether there was syncope in clinical history.The height and body mass of all children were measured, and venous blood were taken to detect blood lipids and serum protein in the morning.Date analysis were conducted with SPSS 22.0 software.Results:(1) The level of triglyceride in the OI group was lower than that in the healthy control group[(0.98±0.45) mmol/L vs. (1.28±1.04) mmol/L], and there was statistically significant( t=2.025, P<0.05); the BMI were respectively (17.56±3.23) kg/m 2 and (16.46±2.58) kg/m 2 in syncope group and non-syncope group, whose result indicated that the BMI in syncope group was higher than that in non-syncope group( t=2.085, P<0.05). (2) The results of binary Logistic regression analysis showed that the triglyceride level was an independent risk factor for OI( OR=0.504, 95% CI: 0.272-0.931, P<0.05). (3) The receiver operating characteristic curve evaluated the predictive value of triacylgly-cerol to OI.Results showed the sensitivity and specificity of OI were respectively 72.1% and 48.2%when the triacylglycerol was 1.09 mmol/L. Conclusions:Low triglyceride level and high BMI may be susceptible factors to OI in children and adolescents.Therefore, the diet of children with OI should be highly valued by clinicians and parents.

ObjectiveTo investigate the risk factors for syncope in children with orthostatic intolerance (OI).Methods The clinical data from 136 children with OI were retrospectively analyzed. The children were divided into syncope group and non-syncope group based on the existence of syncope. Results Among the 136 children, 77 children (56.62%) had syncope and 59 children (43.38%) did not have syncope. The differences in BMI, prevalence of inducement of prolonged standing, prevalence of accompanied symptoms of blurred vision/ blacking out, cold sweating and pallor, prevalence of the history of motion sickness and blood flow velocity of MCA were statistically significant between two groups (P<0.05). Conclusions Children with OI who has low BMI, inducement of prolonged standing, accompanied symptoms of blurred vision/ blacking out, cold sweating and pallor, the history of motion sickness, and fast blood flow velocity of MCA, are prone to syncope.

Objective To discuss the clinical application of different particle size of grain fat sieved by the homogenizing fat extractor.Methods A lot of 68 patients in this group were women,and the average age was 28 years.With the aid of tumescent technique,anterior and lateral thigh fat granules were extracted using liposuction needle;after the homogenizing fat extractor and sieve purification,fat particles were obtained with uniform particle size and no fibrous tissue for different sizes of 2.00 mm,0.90 mm,0.50 mm and 0.28 mm,respectively.After choosing corresponding diameter of fat transplantation needle and appropriate injection level according to fat particle size,the multiple spot and multiple track tunnels,multi-level injection for the facial soft tissue deficiency or cavity were then carried out.With long-term postoperative follow-up,evaluation of different grades were given for the complication,fat survival rate and satisfaction.Results The results were followed up for 3-12 months postoperatively;as responding,the facial appearance of graft field deformity or deficiency was significantly improved and the skin of the recipient area was soft;wrinkles was relieved,and so that they appeared young plump well-pleasing appearance.And there were no complications,such as infection,hematoma,fat liquefaction,pigmentation,induration and so on.Satisfactory results were obtained.Conclusions The treatment of facial soft tissue deficiency or deficiency,by choosing corresponding diameter of fat transplantation needle and appropriate injection level according to the differences of fat particle size sieved by the homogenizing fat extractor,can acheive a high fat survival rate,and stable long-term effect.Thus,this safe and ideal method for rejuvenation of facial treatment is worth promoting.

Objective:To explore the effective ability and strategy of improving in-hospital emergency in large general hospitals through investigating and analyzing the epidemiological characteristics and outcomes of patients treated by rapid response team (RRT) in the Fourth People's Hospital of Shenyang.Methods:The clinical data of 145 patients treated by RRT in the Fourth People's Hospital of Shenyang from April 1st to June 30th in 2019 were retrospectively analyzed. The clinical data including gender, age, RRT response time, disease type, direct cause of RRT initiation, the incidence of cardiac arrest, intensive care unit (ICU) admission rate and outcome were statistically analyzed. The correlation between indicators was analyzed by Pearson correlation. Pareto diagram was used to analyze the direct cause of RRT initiation.Results:A total of 145 patients were treated by RRT within 3 months. The ratio of male ( n = 85) to female ( n = 60) was 1.42∶1. The age of patients treated by RRT was (72.83±14.84) years old, and the response time was (3.27±1.42) minutes. The incidence of cardiac arrest was 23.4% (34/145), and the ICU admission rate was 29.7% (43/145). The hospital mortality was 40.0% (58/145), and the rescue success rate was 60.0% (87/145). Correlation analysis showed that there was a significant positive correlation between the incidence of cardiac arrest and hospital mortality ( r = 0.545, P < 0.01). According to the disease type of patients treated by RRT analysis, respiratory system diseases ( n = 44, 30.3%) accounted for the most, followed by circulatory system diseases ( n = 43, 29.7%), nervous system diseases ( n = 25, 17.2%), digestive system diseases ( n = 19, 13.1%), trauma ( n = 5, 3.4%), endocrine system diseases ( n = 3, 2.1%), urinary system diseases ( n = 2, 1.4%) and others ( n = 4, 2.8%). Further analysis showed that patients aged between 85 years old and 94 years old were prone to the respiratory system diseases, accounting for 48.5% (16/33) of the population in this age group, while the cardiovascular system diseases were the most common in patients older than 55 years old, accounting for 31.0% (40/129) of the population in this age group. Pareto diagram showed that the percentages of direct causes of RRT initiation ranked from high to low, the cumulative percentage of pneumonia ( n = 30, 20.7%), acute myocardial infarction ( n = 26, 17.9%), stroke ( n = 20, 13.8%), septic shock ( n = 14, 9.7%), heart failure ( n = 10, 6.9%), respiratory and cardiac arrest ( n = 9, 6.2%), and gastrointestinal bleeding ( n = 7, 4.8%), which were the main direct causes of RRT initiation with a total of 80%. Conclusions:Respiratory system and circulatory system diseases are the main causes for RRT treatment in first-aid patients in the Fourth People's Hospital of Shenyang. The hospital mortality significantly increases once patients suffered cardiac arrest. The RRT can provide effective intervention earlier and faster, and establish a complete RRT emergency strategy, which is helpful to improve the in-hospital emergency ability in large general hospitals.

OBJECTIVETo determine the relationship between the serum sulfur dioxide, homocysteine and the pulmonary arterial pressure in children with congenital heart defects who generated a pulmonary arterial hypertension syndrome (PAH-CHD), and analyze their role in the pathological process of the disease.

METHODThis was a prospective cohort study, children with systemic pulmonary shunt CHD were selected. The patients were divided into three groups: the CHD with no PAH group:n = 20, 10 males, 10 females, 5 with ventricular septal defect (VSD), 8 with atrial septal defect (ASD) and 7 with patent ductus arteriosus (PDA), mean age (1.9 ± 1.8) years; the CHD with mild PAH group:n = 20, 10 males, 10 females, 12 with VSD, 6 with ASD, and 2 with PDA, mean age (1.0 ± 0.8) year; the CHD with moderate or severe PAH group:n = 20, 8 males, 12 females, 12 with VSD, 6 with ASD, and 1 with PDA, 1 with ASD+VSD, mean age (1.8 ± 1.6) year. Twenty healthy children were enrolled from outpatient department as the control group [included 8 males, 12 females, mean age (1.9 ± 1.5) years]. The homocysteine and SO2 concentrations in the serum samples were detected by a modified high performance liquid chromatographic method with fluorescence detection (HPLC-FD), then, multiple comparisons among the groups were performed with analysis of variance, and the pearson correlation.

RESULTThe serum homocysteine concentrations were respectively (11.0 ± 2.7) , (11.7 ± 2.5), (12.0 ± 2.1), (14.3 ± 3.2) µmol/L in the control group, CHD with no PAH group, CHD with mild PAH group, and CHD with moderate or severe PAH group. According to the multiple comparisons, the CHD with moderate or severe PAH group had the highest level (P all < 0.05) .While the comparison within the control group, CHD with none PAH group, and CHD with mild PAH group, the differences were not significant (P all > 0.05). The serum sulfur dioxide strength (concentrated as SO3(2-)) were respectively (10.6 ± 2.4), (8.9 ± 2.3), (7.3 ± 2.9), (4.3 ± 2.1) µmol/L in the control group, CHD with none PAH group, CHD with mild PAH group, and CHD with moderate or severe PAH group. CHD with moderate or severe PAH group had the highest level of serum sulfur dioxide (P < 0.05) . The pearson correlation analysis indicated that in the CHD children, the serum homocysteine were positively correlated with the pulmonary arterial pressure (r = 0.481, P < 0.01), while, the sulfur dioxide were negatively correlated with pulmonary arterial pressure (r = -0.553, P < 0.01).In all children, the serum homocysteine levels were negatively correlated with the sulfur dioxide (r = -0.231, P = 0.039).

CONCLUSIONThe PAH-CHD children had higher homocysteine levels and lower sulfur dioxide levelsl, which demonstrated the disturbance of homocysteine-sulfur dioxide pathway in the sulfur containing amino acids metabolish in the disease. The homocysteine may become a biological marker which reflecting the severities of the PAH-CHD, while the sulfur dioxide can be a new target for the therapy of PAH-CHD.

Biomarkers ; blood ; Case-Control Studies ; Child, Preschool ; Ductus Arteriosus, Patent ; blood ; complications ; physiopathology ; Familial Primary Pulmonary Hypertension ; blood ; etiology ; physiopathology ; Female ; Heart Defects, Congenital ; blood ; complications ; physiopathology ; Heart Septal Defects ; blood ; complications ; physiopathology ; Hemodynamics ; Homocysteine ; blood ; Humans ; Infant ; Male ; Sulfur Dioxide ; blood