Aux/IAAs interact with auxin response factors (ARFs) to repress their transcriptional activity in the auxin signaling pathway. Previous studies have focused on gain-of-function mutations of domain II and little is known about whether the expression level of wild-type Aux/IAAs can modulate auxin homeostasis. Here we examined the perturbation of auxin homeostasis by ectopic expression of wild-type IAA15. Root gravitropism and stem cell differentiation were also analyzed. The transgenic lines were less sensitive to exogenous auxin and exhibited low-auxin phenotypes including failures in gravity response and defects in stem cell differentiation. Overexpression lines also showed an increase in auxin concentration and reduced polar auxin transport. These results demonstrate that an alteration in the expression of wild-type IAA15 can disrupt auxin homeostasis.
Endothelial inflammation plays a critical role in the development and progression of cardiovascular disease, albeit the mechanisms need to be fully elucidated. We here report that treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor (TNF) α substantially increased the expression of MCP-induced protein 1 (MCPIP1). Overexpression of MCPIP1 protected ECs against TNFα-induced endothelial activation, as characterized by the attenuation in the expression of the adhesion molecule VCAM-1 and monocyte adherence to ECs. Conversely, small interfering RNA-mediated knock down of MCPIP1 increased the expression of VCAM-1 and monocytic adherence to ECs. These studies identified MCPIP1 as a feedback control of cytokines-induced endothelial inflammation.
MCPIP1; Endothelial cell; Inflammation; NF-κB signaling; Adhesion molecule
Invasive fungal infections caused by uncommon fungi have increased in recent years. Hospitalized low-birth-weight infants are at high risk for neonatal fungal infections. Pichia fabianii is a rare pathogen causing blood infection, which has reportedly caused only 4 cases of fungemia and 1 case of endocarditis worldwide. Here, we describe the first case of a P. fabianii blood infection in a premature infant in China.
On July 28th, a low-birth-weight (LBW, 1760 g) female infant born at 33+4 weeks of gestation was admitted to the pediatric intensive care unit with mild neonatal asphyxia. Until August 2nd, a mechanical respirator was used to assist respiration under the Continuous Positive Airway Pressure (CPAP) model. The baby had an increased body temperature and a fever. To prevent infection, Ceftriaxone Sodium (CS) was administered intravenously for three days, after which Cefepime was administered until August 13th. Chest X-rays showed suspected plaque-like shadows in the right lung. Blood cultures twice tested positive for fungal infection caused by Candida pelliculosa (recognized as Pichia fabianii later), which is first mis-identified by commercial kit. Hence, intravenous fluconazole was administered. However, cultures of other body fluids (e.g., urine, feces and sputum) tested negative for fungal infection. Routine tests and biochemistry of cerebrospinal fluid (CSF) were normal. Latex agglutination of Cryptococcus neoformans and fungi cultures in the CSF were also negative. After 14 days of intravenous fluconazole, blood was re-cultured, the result of which was negative. On August 30th, intravenous fluconazole was suspended. On Sep 3rd, the infant left the hospital in good health.
This is the first case of a blood infection caused by P. fabianii in a LBW premature female infant in China. Risk factors for fungal infection include premature birth, as well as mechanical invasive operation and antibacterial drug usage. Whether such risk factors necessitate prophylactic use of antifungal drugs is an important question that has yet to be fully addressed. Additionally, the pathogen P. fabianii collected in this study was resistant to amphotericin B (AMB) and itraconazole (ITR). With the exception of the azole-resistant endocarditis case, all other cases have not demonstrated such a resistance. Finally, commercial biochemical methods used in routine practice are limited in their ability to identify P. fabianii. Molecular genetic based methods are imperative for identification of uncommon fungal species from disseminated infections.
Pichia fabianii; Fungemia; Infant infection
Glycolipids presented by the major histocompatibility complex class I (MHC I) homolog CD1d are recognized by natural killer T (NKT) cells characterized by either a semi-invariant (type I or iNKT) or a relatively variable (type II) T cell receptor (TCR) repertoire. Here we describe the first structure of a type II NKT TCR complexed with CD1d-lysosulfatide (LSF). Both TCR α and β chains contacted the CD1d molecule with a diagonal footprint, typical of MHC-TCR interactions, while the antigen was recognized exclusively with a single TCR chain, similar to the iNKT TCR. Type II NKT cells, therefore, recognize CD1d-sulfatide complexes with a distinct recognition mechanism characterized by features of both iNKT cells as well as conventional peptide-reactive T cells.
To test the hypothesis that family intervention to promote effective parenting in early childhood affects obesity in preadolescence.
Participants were 186 minority youth at risk for behavior problems who enrolled in long-term follow-up studies after random assignment to family intervention or control condition at age 4. Follow-up Study 1 included 40 girls at familial risk for behavior problems; Follow-up Study 2 included 146 boys and girls at risk for behavior problems based on teacher ratings. Family intervention aimed to promote effective parenting and prevent behavior problems during early childhood; it did not focus on physical health. BMI and health behaviors were measured an average of 5 years after intervention in Study 1 and 3 years after intervention in Study 2.
Youth randomized to intervention had significantly lower BMI at follow-up relative to controls (Study 1 P = .05; Study 2 P = .006). Clinical impact is evidenced by lower rates of obesity (BMI ≥95th percentile) among intervention girls and boys relative to controls (Study 2: 24% vs 54%, P = .002). There were significant intervention-control group differences on physical and sedentary activity, blood pressure, and diet.
Two long-term follow-up studies of randomized trials show that relative to controls, youth at risk for behavior problems who received family intervention at age 4 had lower BMI and improved health behaviors as they approached adolescence. Efforts to promote effective parenting and prevent behavior problems early in life may contribute to the reduction of obesity and health disparities.
obesity; prevention; child; early childhood; families
Objective: Weed pollens are common sources of allergens worldwide. The prevalence of weed pollen sensitization is not yet fully known in China. The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia, Ambrosia, and Humulus in northern China. Methods: A total of 1 144 subjects (aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources. Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris, Ambrosia artemisiifolia, and Humulus scandens, and against the purified allergens, Art v 1 and Amb a 1. Results: Of 1 144 subjects, 170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing. The prevalence of positive intradermal responses to pollens of Artemisia sieversiana, Artemisia annua, A. artemisiifolia, and H. scandens was 11.0%, 10.2%, 3.7%, and 6.6%, respectively. Among the intradermal positive subjects, the prevalence of specific IgE antigens to A. vulgaris was 58.3%, to A. artemisiifolia 14.7%, and to H. scandens 41.0%. The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%, and to Amb a 1 was 11.2%. The correlation between the presence of IgE antibodies specific to A. vulgaris and to the Art v 1 antigen was very high. Subjects with A. artemisiifolia specific IgE also had A. vulgaris specific IgE, but with relatively high levels of A. vulgaris IgE antibodies. There were no correlations between the presence of IgE antibodies to H. scandens and A. vulgaris or to H. scandens and A. artemisiifolia. Conclusions: The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%. Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.
Humulus scandens; Artemisia vulgaris; Ambrosia artemisiifolia; Intradermal test; Specific IgE; Sensitization
A brain-to-brain interface (BTBI) enabled a real-time transfer of behaviorally meaningful sensorimotor information between the brains of two rats. In this BTBI, an “encoder” rat performed sensorimotor tasks that required it to select from two choices of tactile or visual stimuli. While the encoder rat performed the task, samples of its cortical activity were transmitted to matching cortical areas of a “decoder” rat using intracortical microstimulation (ICMS). The decoder rat learned to make similar behavioral selections, guided solely by the information provided by the encoder rat's brain. These results demonstrated that a complex system was formed by coupling the animals' brains, suggesting that BTBIs can enable dyads or networks of animal's brains to exchange, process, and store information and, hence, serve as the basis for studies of novel types of social interaction and for biological computing devices.
Interleukin-10 (IL-10) is a multifunctional cytokine which participates in the development and progression of various malignant tumors. To date, a number of case–control studies were conducted to detect the association between IL-10-592C>A polymorphism and cancer risk in humans. However, the results of these studies on the association remain conflicting. In an effort to solve this controversy, we performed a meta-analysis based on 70 case–control studies from 65 articles, including 16 785 cancer cases and 19 713 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results suggested that the variant homozygote genotype AA of the IL-10-592C>A polymorphism was associated with a moderately decreased risk of all cancer types (OR = 0.90, 95% CI = 0.83–0.98 for homozygote comparison, OR = 0.92, 95% CI = 0.86–0.98 for recessive model). In the stratified analyses, the risk remained for studies of smoking-related cancer, Asian populations and hospital-based studies. These results suggested that the IL-10-592C>A polymorphism might contribute to the cancer susceptibility, especially in smoking-related cancer, Asians and hospital-based studies. Further studies are needed to confirm the relationship.
The current report detailed an investigation of melamine-linked urinary stones in children exposed to contaminated formula.
Material and methods
A total of 1062 children fed with melamine-contaminated infant formula were screened for urinary stones. Sixty healthy children without melamine exposure were recruited as a control group. Ultrasonography of the urinary tract system was performed. Urinalysis, renal function, liver status, and serum electrolytes were determined.
We encountered 49 affected children from the 1062 screened ones, at a rate of 4.6% per ultrasound performed. Thirty-two were male, and 17 were female. The affected children ranged in age from 1 month to 96 months, with a mean of 25 months. Duration of exposure was from 1.3 months to 84 months, with a mean of 19.5 months. The melamine contents in serum were between 12 mg/kg and 2563 mg/kg, with mean concentration of 1295.3 mg/kg. Most affected children were asymptomatic with no urinary findings. Patients with urinary stones exhibited lower urine pH and serum HCO3
– than those in the healthy children, whereas for serum uric acid, alanine aminotransferase, aspartate aminotransferase, and anion gap the opposite trends were observed. The stone diameter ranged from 2 mm to 18 mm with a median of 6.5 mm. Multiple stones were noted in all patients. After 1 week of conservative management, stone diameters of 38 cases (77.6%) were significantly decreased. Among them, urinary stones were discharged completely in 21 affected children (42.9%).
The short-term outcome of melamine-linked urinary stones is satisfactory.
urinary stone; melamine; ultrasound; urinalysis; childhood
Triple negative breast cancer (TNBC) acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A) expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025), the proliferation marker Ki-67 (P = 0.001), and the recurrence rate of TNBC patients (P<0.001). In TNBC patients with Aur-A high expression, the risk of distant recurrence peaked at the first 3 years and declined rapidly thereafter, whereas patients with Aur-A low expression showed a relatively constant risk of recurrence during the entire follow-up period. Univariate and multivariate analysis showed that overexpression of Aur-A predicted poor overall survival (P = 0.002) and progression-free survival (P = 0.012) in TNBC. Furthermore, overexpression of Aur-A, associated with high Ki-67, predicted an inferior prognosis compared with low expression of both Aur-A and Ki-67. Importantly, we further found that Aur-A was overexpressed in TNBC cells, and inhibition of this kinase inhibited cell proliferation and prevented cell migration in TNBC. Our findings demonstrated that Aur-A was a potential therapeutic target for TNBC and inhibition of Aur-A kinase was a promising regimen for TNBC cancer therapy.
Regulation of forebrain cellular structure and function by small GTPase pathways is crucial for normal and pathological brain development and function. Kalirin is a brain-specific activator of Rho-like small GTPases implicated in neuropsychiatric disorders. We have recently demonstrated key roles for kalirin in cortical synaptic transmission, dendrite branching, spine density, and working memory. However, little is known about the impact of the complete absence of kalirin on the hippocampus in mice. We thus investigated hippocampal function, structure, and associated behavioral phenotypes in KALRN knockout (KO) mice we have recently generated. Here we show that KALRN KO mice had modest impairments in hippocampal LTP, but normal hippocampal synaptic transmission. In these mice, both context and cue-dependent fear conditioning were impaired. Spine density and dendrite morphology in hippocampal pyramidal neurons was not significantly affected in the KALRN KO mice, but small alterations in the gross morphology of the hippocampus were detected. These data suggest that hippocampal structure and function are more resilient to the complete loss of kalirin, and reveal impairments in fear learning. These studies allow the comparison of the phenotypes of different kalirin mutant mice and shed light on the brain region-specific functions of small GTPase signaling.
GEF; synaptic plasticity; dendrite; dendritic spine; Rac1; knockout; fear conditioning
Background and Purpose
Recently, we invented a computerized endoscopic balloon manometry (CEBM) to measure variceal pressure (VP) in cirrhotic patient. The purpose of this study was to evaluate the reliability and feasibility of this method, and whether this technique provided further information to pharmacological therapy.
Patients and Methods
VP measurements were performed in 83 cirrhotic patients and compared with HVPG as well as endoscopic bleeding risk parameters. Furthermore, VP was assessed before and during propranolol therapy in 30 patients without previous bleeding.
VP measurements were successful in 96% (83/86) of all patients. Of the 83 patients, the VP correlated closely with the HVPG (P<0.001). The presence of red colour signs and the size of varices were strongly associated with VP. Patients with previous bleeding had higher VP than those who had not yet experienced bleeding. In univariate analysis, the level of VP, the size of varices, and red color signs predicted a higher risk of bleeding. The multiple logistic regression model revealed that VP was the major risk factor for bleeding. In 30 patients receiving propranolol, VP significantly decreased from 21.1±3.5 mmHg before therapy to 18.1±3.3 mmHg after 3 months and to 16.3±4.0 mmHg after 6 months. Comparing the mean decrease in VP with that in hepatic venous pressure gradient (HVPG), the decrease in VP was more obvious than HVPG response to propranolol.
This study showed that CEBM is safe and practical to assess VP in cirrhotic patient. It has the potential to be used as a clinical method to assess the risk of variceal bleeding and the effects of pharmacological therapy.
Effect of vasoactive drugs on esophageal variceal hemodynamics in patients with portal hypertension. Chinese Clinical Trial Registry –TRC-08000252.
Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.
To investigate the effect of Y-27632 on the survival and neurite outgrowth of the cultured retinal neurocytes.
After the postnatal day 2-3, Sprague-Dawley retinal neurocytes were cultured for 48 hours, the culture media was replaced with serum-free media (control group) and serum-free media contained 30µmol/L Y-27632 (Y-27632 group), and the cells were continually cultured another 48 hours. The cultured retinal neurocytes were identified with anti-neuron specific enolase (NSE) immunocytochemistry. The survival state of those cells was estimated by MTT assay, and the neurite outgrowth of those cells was evaluated by the computerized image-analysis system.
Compared with the control group, the absorbance values of cells survival in Y-27632 group increased 12.90% and 33.33% respectively after 72 and 96 hours culture. Y-27632 had no significant effect on the diameter of cultured retinal neurocytes. Compared with the control group, Y-27632 induced a stable improvement of neurite outgrowth of retinal neurocytes after 72 and 96 hours culture (P=0.001).
Y-27632 could promote the survival and neurite outgrowth of the early postnatal cultured retinal neurocytes.
Y-27632; retinal neurocytes; cell culture; neurites
AIM: To give a comprehensive report of E-cadherin gene (CDH1) variations in a population at a high risk for gastric cancer (GC).
METHODS: The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years. A total of 240 cancer-free controls were recruited (mean age of 61.8 ± 10.1 years, age range of 26-82 years). Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing. Luciferase reporter assay, RNA splicing assay and bioinformatic analysis were used to evaluate the effect of mutations.
RESULTS: Four novel CDH1 sequence alterations were identified in GC patients including a G>T transition 49 bp before the start codon; a three-nucleotide deletion, c.44_46del TGC; one missense mutation, c.604G>A (V202I); and one variation in the intron, c.1320+7A>G. In addition, polymorphism frequencies were observed for CDH1-164delT, -161C>A, -73A>C, c.48+6C>T, c.48+62_48+63delinsCGTGCCCCAGCCC, c.894C>T (A298A), c.1224G>A (A408A), c.1888C>G (L630V), c.2076T>C (A692A), and c.2253C>T (N751N) which is similar to the data reported in http://www.ncbi.nlm.nih.gov/projects/SNP/. RNA splicing analysis suggested that the c.1320+7A>G and c.1224G>A variations did not affect exon splicing ability. Luciferase reporter assay demonstrated that the c.-49T variation might be helpful for E-cadherin transcription, though the increase in transcription activity is limited (only 33%). SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function, while the V202I variant does not.
CONCLUSION: This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes.
Gastric cancer; Germline mutation; CDH1; Luciferase reporter assay; RNA splicing analysis
A hybrid multiscale and multilevel image fusion algorithm for green fluorescent protein (GFP) image and phase contrast image of Arabidopsis cell is proposed in this paper. Combining intensity-hue-saturation (IHS) transform and sharp frequency localization Contourlet transform (SFL-CT), this algorithm uses different fusion strategies for different detailed subbands, which include neighborhood consistency measurement (NCM) that can adaptively find balance between color background and gray structure. Also two kinds of neighborhood classes based on empirical model are taken into consideration. Visual information fidelity (VIF) as an objective criterion is introduced to evaluate the fusion image. The experimental results of 117 groups of Arabidopsis cell image from John Innes Center show that the new algorithm cannot only make the details of original images well preserved but also improve the visibility of the fusion image, which shows the superiority of the novel method to traditional ones.
Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.
Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93–1.26; additive model: OR = 1.33, 95%CI = 0.81–2.17; dominant model: OR = 1.00, 95%CI = 0.86–1.15; recessive model: OR = 1.06, 95%CI = 0.77–1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88–1.41; additive model: OR = 1.36, 95%CI = 0.60–3.09; dominant model: OR = 1.25, 95%CI = 0.74–2.11; recessive model: OR = 2.17, 95%CI = 1.11–4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.
This meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.
Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) play a critical role in cancer cell growth and resistance to therapy. Most mutations occur at codons 12 and 13. In colorectal cancer, the presence of any mutant KRas amino acid substitution is a negative predictor of patient response to targeted therapy. However, in non–small cell lung cancer (NSCLC), the evidence that KRAS mutation is a predictive factor is conflicting.
We used data from a molecularly targeted clinical trial for 215 patients with tissues available out of 268 evaluable patients with refractory NSCLC to examine associations between specific mutant KRas proteins and progression-free survival and tumor gene expression. Transcriptome microarray studies of patient tumor samples and reverse-phase protein array studies of a panel of 67 NSCLC cell lines with known substitutions in KRas and in immortalized human bronchial epithelial cells stably expressing different mutant KRas proteins were used to investigate signaling pathway activation. Molecular modeling was used to study the conformations of wild-type and mutant KRas proteins. Kaplan–Meier curves and Cox regression were used to analyze survival data. All statistical tests were two-sided.
Patients whose tumors had either mutant KRas-Gly12Cys or mutant KRas-Gly12Val had worse progression-free survival compared with patients whose tumors had other mutant KRas proteins or wild-type KRas (P = .046, median survival = 1.84 months) compared with all other mutant KRas (median survival = 3.35 months) or wild-type KRas (median survival = 1.95 months). NSCLC cell lines with mutant KRas-Gly12Asp had activated phosphatidylinositol 3-kinase (PI-3-K) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) signaling, whereas those with mutant KRas-Gly12Cys or mutant KRas-Gly12Val had activated Ral signaling and decreased growth factor–dependent Akt activation. Molecular modeling studies showed that different conformations imposed by mutant KRas may lead to altered association with downstream signaling transducers.
Not all mutant KRas proteins affect patient survival or downstream signaling in a similar way. The heterogeneous behavior of mutant KRas proteins implies that therapeutic interventions may need to take into account the specific mutant KRas expressed by the tumor.
AIM: To compare the efficacy of modified percutaneous transhepatic variceal embolization (PTVE) with 2-octyl-cyanoacrylate (2-OCA) and endoscopic variceal obturation (EVO) with an injection of 2-OCA for prophylaxis of gastric variceal rebleeding.
METHODS: In this retrospective study, the medical records of liver cirrhosis patients with gastric variceal bleeding who underwent either endoscopic 2-OCA (EVO) or modified PTVE using 2-OCA at Shandong Provincial Hospital from January 2006 to December 2008 were reviewed. Patient demographics, rebleeding rate, survival rate, and complications were compared between the two groups (PTVE and EVO). All results were expressed as mean ± SD, or as a percentage. Quantitative variables were compared by two sample Student t tests, and qualitative variables were compared by the Fisher exact test or the χ2 test (with Yates correction) where appropriate. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 13.0 software.
RESULTS: A total of 77 patients were included; 45 patients who underwent EVO and 32 patients who received PTVE. During the follow-up (19.78 ± 7.70 mo in the EVO group, vs 21.53 ± 8.56 mo in the PTVE group) rebleeding occurred in 17 patients in the EVO group and in 4 patients in the PTVE group (37.78% vs 12.5%, P = 0.028). The cumulative rebleeding-free rate was 75%, 59%, and 49% in 1, 2, and 3 years respectively for EVO, and 93%, 84%, and 84% for PTVE (P = 0.011). Cox analysis was used to identify independent factors that predicted rebleeding after treatment. Variables including age, gender, cause, Child-Pugh classification, size of gastric varices (GV), location of GV, and treatment methods were analyzed. It was revealed that Child-Pugh classification [risk ratio (RR) 2.10, 95%CI: 1.03-4.28, P = 0.040], choice of treatment (RR 0.25, 95%CI: 0.08-0.80, P = 0.019), and size of GV (RR 2.14, 95%CI: 1.07-4.28, P = 0.032) were the independent factors for predicting rebleeding. Follow-up computed tomography revealed that cyanoacrylate was retained in the varices and in the feeding veins of PTVE patients. During the follow-up, eight patients in the EVO group and four patients in the PTVE group died. The cumulative survival rates at 1, 2, and 3 years were 93%, 84%, and 67% respectively in the EVO group, and 97%, 88%, and 74% respectively in the PTVE group. The survival rates were not significantly different between the two groups (P = 0.432). Cox analysis showed that the Child-Pugh classification was the most significant prognostic factor of survival (RR 2.77, 95%CI: 1.12-6.80, P = 0.027). The incidence of complications was similar in both groups.
CONCLUSION: With extensive and permanent obliteration of gastric varices and its feeding veins, PTVE with 2-OCA is superior to endoscopic 2-OCA injection for preventing gastric variceal rebleeding.
Gastric varices; Endoscopic variceal obturation; Percutaneous transhepatic variceal embolization; 2-octyl-cyanoacrylate; Bleeding
This paper reports studies of two patients proven by a variety of studies to have mitochondrial depletion syndromes due to mutations in either their MPV17 or DGUOK genes. Each was initially investigated metabolically because of plasma methionine concentrations as high as 15–21-fold above the upper limit of the reference range, then found also to have plasma levels of S-adenosylmethionine (AdoMet) 4.4–8.6-fold above the upper limit of the reference range. Assays of S-adenosylhomocysteine, total homocysteine, cystathionine, sarcosine, and other relevant metabolites and studies of their gene encoding glycine N-methyltransferase produced evidence suggesting they had none of the known causes of elevated methionine with or without elevated AdoMet. Patient 1 grew slowly and intermittently, but was cognitively normal. At age 7 years he was found to have hepatocellular carcinoma, underwent a liver transplant and died of progressive liver and renal failure at age almost 9 years. Patient 2 had a clinical course typical of DGUOK deficiency and died at age 8 ½ months. Although each patient had liver abnormalities, evidence is presented that such abnormalities are very unlikely to explain their elevations of AdoMet or the extent of their hypermethioninemias. A working hypothesis is presented suggesting that with mitochondrial depletion the normal usage of AdoMet by mitochondria is impaired, AdoMet accumulates in the cytoplasm of affected cells poor in glycine N-methyltransferase activity, the accumulated AdoMet causes methionine to accumulate by inhibiting activity of methionine adenosyltransferase II, and that both AdoMet and methionine consequently leak abnormally into the plasma.
mitochondria; depletion; methionine; S-adenosylmethionine; MPV17; DGUOK
To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction.
We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs.
Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling.
We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients.
beta-catenin; prostate cancer; androgen receptor; hyaluronan synthase
Cancer stem cells (CSCs) are thought to be capable of surviving conventional chemotherapeutic treatments because the cells have more resistant to anticancer drugs than common cancer cells. Most in vitro studies in experimental cancer cells have been done in a two-dimensional (2D) monocultures, while accumulating evidence suggests that cancer cells behave differently when they are grown within a three-dimensional (3D) culture system.
The CD44+CD117+cells isolated from human epithelial ovarian cancer SKOV-3 cell line using magnetic-activated cell sorting were found to grow faster than the SKOV-3 cells in the 3D culture and in the nude mice. Anticancer drugs 5FU, docetaxel, cisplatin, and carboplatin were seen to inhibit growth of the CD44+CD117+ cells by 50% in the 2D culture with IC50 concentration, whereas, in the 3D culture, the four drugs inhibited the cell growth by only 34.4%, 40.8%, 34.8% and 21.9% at 3D one, respectively. Effect of paclitaxel on the CD44+CD117+cell viability indicated that fewer cells underwent apoptosis in 3D culture than that in 2D one. In addition, anticancer drugs markedly increased the expression of ABCG2 and ABCB1 of CD44+CD117+cells in 3D culture.
Our assay demonstrated that human epithelial ovarian cancer CD44+CD117+cells possessed the properties of CSCs that exhibited more chemoresistance in the 3D culture than that of in 2D one. The 3D culture provides a realistic model for study of the CSC response to anticancer drugs.
Three-dimensional culture; Epithelial ovarian cancer; Cancer stem cells; Chemoresistance
Very little is known about swine influenza in northwestern China. Here, we report the complete genomic sequences of six avian-like H1N1 swine influenza viruses (SIVs) isolated in pigs in northwestern China. Phylogenetic analyses of the sequences of eight genomic segments demonstrated that they are avian-like H1N1 SIVs.
This study tested whether IL-17A is involved in the pathogenesis of mouse myocardial ischemia-reperfusion (I/R) injury and investigated the mechanisms.
Inflammatory processes play a major role in myocardial I/R injury. We recently identified interleukin (IL)-17A as an important cytokine in inflammatory cardiovascular diseases such as atherosclerosis and viral myocarditis. However, its role in myocardial I/R injury remains unknown.
The involvement of IL-17A was assessed in functional assays in mouse myocardial I/R injury by neutralization/repletion or genetically deficiency of IL-17A, and its mechanism on cardiomyocyte apoptosis and neutrophil infiltration were further studied in vivo and in vitro.
IL-17A was elevated following murine left coronary artery ligation and reperfusion. Intracellular cytokine staining revealed that γδT lymphocytes, but not CD4+ helper T cells, were a major source of IL-17A. Anti-IL-17A mAb treatment or IL-17A knockout markedly ameliorated I/R injury, as demonstrated by reduced infarct size, reduced cardiac troponin T levels and improved cardiac function. This improvement was associated with a reduction in cardiomyocyte apoptosis and neutrophil infiltration. On the contrary, repletion of exogenous IL-17A induced the opposite effect. In vitro study showed that IL-17A mediated cardiomyocyte apoptosis through regulating the Bax/Bcl-2 ratio, induced CXC chemokine-mediated neutrophil migration and promoted neutrophil-endothelial cell adherence through induction of endothelial cell E-selectin and inter-cellular adhesion molecule (ICAM)-1 expression.
IL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration.
interleukin-17; inflammation; ischemia/reperfusion; γδT cell