RUNX2 Regulates Osteoblast Differentiation via the BMP4 Signaling Pathway.

RUNX2 is a master osteogenic transcription factor, and mutations in RUNX2 cause the inherited skeletal disorder cleidocranial dysplasia (CCD). Studies have revealed that RUNX2 is not only a downstream target of the bone morphogenetic protein (BMP) pathway but can also regulate the expression of BMPs. However, the underlying mechanism of the regulation of BMPs by RUNX2 remains unknown. In this project, we diagnosed a CCD patient with a 7.86-Mb heterozygous deletion on chromosome 6 containing all exons of RUNX2 by multiplex ligation-dependent probe amplification (MLPA) and whole-genome sequencing (WGS). Bone marrow mesenchymal stem cells (BMSCs) were further extracted from patient alveolar bone fragments (CCD-BMSCs), an excellent natural model to explore the possible mechanism. The osteogenic differentiation ability of CCD-BMSCs was severely affected by RUNX2 heterozygous deletion. Also, BMP4 decreased most in BMP ligands, and CHRDL1, a BMP antagonist, was abnormally elevated in CCD-BMSCs. Furthermore, BMP4 treatment essentially rescued the osteogenic capacity of CCD-BMSCs, and RUNX2 overexpression reversed the abnormal expression of BMP4 and CHRDL1. Notably, we constructed CRISPR/Cas9 Runx2+/m MC3T3-E1 cells, which simulated a variant in CCD-BMSCs, to exclude the interference of other gene deletions and the heterogeneity of the genetic background of primary cells, and verified all findings from the CCD-BMSCs. Moreover, the luciferase reporter experiment showed that RUNX2 could inhibit the transcription of CHRDL1. Through immunofluorescence, the inhibitory effect of CHRDL1 on BMP4/Smad signaling was confirmed in MC3T3-E1 cells. These results revealed that RUNX2 regulated the BMP4 pathway by inhibiting CHRDL1 transcription. We collectively identified a novel RUNX2/CHRDL1/BMP4 axis to regulate osteogenic differentiation and noted that BMP4 might be a valuable therapeutic option for treating bone diseases.

[Eltrombopag for thrombocytopenia in 24 children after hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT). Methods: Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups. Results: Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group (n=8), the course and total dose of eltrombopag in umbilical cord blood group (n=16) were significantly reduced(24.5 (8.0-81.0) vs. 65.5 (35.0-90.0) d, Z=-3.004, P=0.002; 900.0 (200.0-3 850.0) vs. 2 862.5 (1 175.0-5 900.0) mg, Z=-2.604, P=0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P>0.05). Comparing malignant patients (n=12) and non-malignant patients (n=12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P>0.05). Conclusion: Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.

[Safety evaluation on different ventilation strategies set for neonatal respiratory distress syndrome: a network Meta-analysis].

Objective: To evaluate the relative safety of different ventilation methods regarding mortality and rates of complication, on neonatal respiratory distress syndrome (NRDS). Methods: Network Meta-analysis was used to collect data on randomized controlled trials of pulmonary ventilation strategies in preterm infants with a mean gestational age of less than 32 weeks. Diagnostic criteria on NRDS were published in the PubMed, Cochrane, Web of Science, EBSCO, and Springer Link databases from January 1986 to June 2018. Revman 5.3 software was used to evaluate the quality of studies, based on the Cochrane quality assessment tool. Data were analyzed by Bayesian and frequency methods, using both Win BUGS 1.4.3 and STATA 13.0 software. Safety of different ventilation strategies for NRDS mortality and complications would include intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA) and retinopathy of prematurity (ROP) and were evaluated. Counted data was displayed by OR and 95%CI. Results: A total of 31 RCTs were included in this paper, including 5 827 preterm infants and 11 ventilation strategies. There were no statistically significant differences appearing in 11 ventilation strategies on mortality, PDA or ROP. IVH results were reported in 28 studies. Compared with nasal intermittent positive pressure ventilation (NIPPV), both high- frequency oscillation ventilation (HFOV) (OR=3.33, 95%CI: 1.08-16.67, P<0.05) and synchronized intermittent mechanical ventilation (SIMV) (OR=8.22, 95%CI: 1.25-29.44, P<0.05) schemes seemed to have increased the risk of IVH in preterm infants with NRDS. NIPPV appeared the optimal ventilation strategy in the rankings of cumulative probability. Results on clustering showed that NIPPV was probably the best ventilation strategy for children with NRDS after considering the orders of IVH, PDA and ROP on mortality, respectively. However, HFOV, IMV, and SIMV did not seem to be the ideal ventilated strategies. Conclusions: Most of the clinical decision makers might prefer using NIPPV in the treatment of children with NRDS through mechanical ventilation systems to reduce both the incidence and death caused by IVH, PDA and ROP. It was not recommended to use HFOV, SIMV and IMV in treating NRDS with gestational less than 32 weeks. We suggested that larger numbers of multi-center RCTs ba carried out to make the above conclusions more convincing.

Circ-DONSON promotes malignant progression of glioma through modulating FOXO3.

OBJECTIVE: The aim of this study was to investigate the expression level of circ-DONSON in glioma and to explore its effect on glioma metastasis and the underlying mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine circ-DONSON expression in 40 paired glioma tumor tissues and adjacent tissues. Meanwhile, the relation between circ-DONSON level and clinical parameters of glioma and the prognosis of patients was analyzed. The expression of circ-DONSON in glioma cell lines was analyzed by qRT-PCR as well. In addition, circs-DONSON silencing model was constructed in glioma cell lines. Cell counting kit-8 (CCK-8), cell scratch, and transwell migration assays were performed to investigate the effect of circ-DONSON on biological functions of glioma cells. Finally, the interplay between FOXO3 and circ-DONSON was explored. RESULTS: QRT-PCR results revealed that the expression level of circ-DONSON in glioma tumor tissues was remarkably higher than that of adjacent tissues, and the difference was statistically significant (p<0.05). Compared with patients with low expression of circ-DONSON, significantly higher prevalence of lymph node or distant metastasis and worse prognosis were observed in patients with high expression of circ-DONSON (p<0.05). The proliferation and migration abilities of glioma cells in circ-DONSON silenced group were remarkably suppressed when compared with NC group (p<0.05). Additionally, FOXO3 expression was remarkably down-regulated in glioma cell lines and tissues. FOXO3 expression was negatively correlated with circ-DONSON expression. In addition, cell reverse experiment demonstrated that circ-DONSON and FOXO3 can regulate each other, thereby together affecting the malignant progression of glioma. CONCLUSIONS: Circ-DONSON was remarkably associated with lymph node or distant metastasis, as well as poor prognosis of patients with glioma. Furthermore, it promoted the metastasis of glioma cells via regulating FOXO3.

Effects of different starch sources on glucose and fat metabolism in broiler chickens.

1. The aim of the present study was to investigate the effects of different starch sources (corn, wheat, and rice) on the blood glucose level, glycogen content of liver and muscle, expression of GSK-3ß and FAS mRNA, abdominal fat weight and abdominal fat deposition in broiler chickens. 2. A total of 360, one-day-old AA (Arbor Acres) broiler chickens were randomly assigned to three treatment groups, each with six replicates, consisting of 20 chickens per replicate, and fed either a corn-, wheat- or rice-based diet for 21 days. The chickens were then subdivided into groups A and B, and the chickens in these two subgroups were processed or sampled for 28 days, respectively. 3. The results indicated that post-prandial time significantly affected the glucose concentration, glycogen content in the liver and breast muscle and expression of GSK-3ß and FAS mRNAs (P < 0.05). The expression of the GSK-3ß gene in the chicken liver of the corn-based diet group was higher (P < 0.05) than that in the wheat-based diet group, and the expression of the FAS gene in the corn-based diet group was lower (P < 0.05) than that in the wheat-based and rice-based diet groups. Abdominal fat weight and deposition in the corn-based diet group were lower than those of the wheat-based and rice-based diet groups, but these differences were not significant (P > 0.05). 4. The results suggested that the efficiency of glucose absorption in animals might have an effect on the fat deposition efficiency in the liver and that diets with different starch sources might affect fat deposition in chickens.

[Differences of brain functional alterations between subtypes of Cushing's syndrome patients].

Objective: To compare the differences of brain functional damage of subtypes of patients with Cushing's syndrome (CS). Methods: A total of 11 adrenocorticotropic hormone (ACTH)-dependent CS patients and 29 ACTH-independent CS patients were recruited from Chinese PLA General Hospital between September 2015 and March 2017 with confirmed CS. The psychiatric scales and brain task functional magnetic resonance imaging (fMRI) were evaluated. Results: A total of 40 patients (34 females, 6 males) with a mean age of (39.20±12.10) years and a median education level of 12 (9, 16) years were enrolled. ACTH-dependent patients had significantly worse performance than the ACTH-independent patients in response to the depression evaluation (64.6±6.1 vs 56.2±12.8, P=0.008), positive emotion (17.8±4.2 vs 24.3±7.2, P=0.008) and CS life quality [31(29,33) vs 42(29,51), P=0.040]. In the reaction to positive target pictures, ACTH-dependent CS patients showed stronger activation in left superior temporal gyrus compared with patients in ACTH-independent group, while the activation degree of their bilateral dorsal anterior cingulate cortex, bilateralsuperior frontal gyrus and left middle frontal gyrus was much worse. In the reactions to negative target pictures, ACTH-dependent CS patients had weaker activation in bilateral cerebellum, left superior frontal gyrus, left middle frontal gyrus, left precuneus and right postcentral gyrus, compared with patients in the ACTH-independent CS group (P<0.01, AlphaSim corrected). The activation degree of some regions whose brain function was different between the two groups was correlated to the cortisol level, ACTH level, 24 h urinary free cortisol (UFC) level, depression evaluation and negative emotion assessment (all P<0.05). Conclusions: The severity of the depression and the life quality of patients in ACTH-dependent group are worse than ACTH-independent CS patients. The brain function of ACTH-dependent CS patients is much weaker.

[Effect of comprehensive AIDS intervention among men aged 50 or over who had non-marital sexual behavior].

Objective: To evaluate the effectiveness of AIDS intervention programs on men aged 50 or over and having had non-marital sexual behavior. Methods: A community-based intervention/experimental and based on individual level study was adopted. Stratified sampling method was used. 12 townships/streets in Fuyang district of Hangzhou were identified as intervention or control group (six research sites each). All of the subjects in the township (street) were included. The inclusion criteria of study objects would include men aged 50 or older who reported having unmarried sex in the last year. Estimated sample size was 290, with each 145 in the intervention group and the control group. All the intervention group participants were provided with a total of 4 intervention-related items (knowledge and education on AIDS prevention, information radiation and behavioral change, broadcast expert lectures), every 3 months, for 12 month, the main evaluation indicators would include: incidence of non-marital sex and commercial sex in the last year, condom use when having non-marital sex in the last episode. Results: A total of 312 subjects were recruited. 300 of them completed the baseline study while 284 of them completed the follow-up survey. Among the subjects who had undergone the baseline study, the average age was (65.58±7.89), 71.33% were married or cohabiting with someone, 52.00% having had primary school education. After the implementation of intervention programs, the incidence of non-marital sex dropped to 59.42% (82/138) and the incidence of commercial sex dropped from 79.73% (118/148) to 55.07% (76/138). Condom use rate in the last non-marital sexual contact increased from 19.59% (29/148) to 51.22% (42/82). In the control group, the incidence of non-marital sex in the year before dropped to 74.66% (109/146) and the incidence of commercial sex dropped from 91.45% (139/152) to 72.60% (106/146). Rates of condom use during the last non-marital sexual contact dropped from 32.89% (50/152) to 31.19% (34/109). Statistically, there were significant differences appeared between the two groups on the incidence of non-marital sex in the past year (χ(2)=7.48, P=0.008), the incidence of commercial sex in the last year (χ(2)=9.47, P=0.003) and the rate of condom use in the last sex experience (χ(2)=7.83, P=0.007). Conclusions: Results from this intervention study showed that: in the intervention group, both the incidence rates of non-marital or commercial sex had reduced, together with the increase of condom use in non-marital sex in the last sexual experience. Intervention strategies that involving knowledge and education on AIDS prevention, information radiation and behavioral change, broadcasting lectures by experts etc. were all proved effective.

Relationship between the change in pacing threshold and the myocardial injury.

OBJECTIVE: To investigate the effects of general conditions and past medical history of patients on the short-term pacing threshold after the implantation of active electrodes of a cardiac pacemaker, and to understand whether the application of active electrodes will cause muscle injury and the severity of the injury. PATIENTS AND METHODS: A total of 156 patients who were treated with a cardiac pacemaker and implanted with single or double active electrodes in Cardiovascular Department of Central Hospital of Jiangjin District were enrolled, including 96 patients treated with a single active electrode and 60 patients treated with double active electrodes. Their clinical data were collected. During operation, the short-term atrial and ventricular pacing thresholds were monitored and recorded after the implantation of the active fixed electrode lead. RESULTS: Multivariate Logistic regression analysis showed that female sex, age, smoking, drinking, coronary heart disease, diabetes mellitus and hyperlipidemia had effects on pacing thresholds in a short-term to some extent after the implantation of active fixed electrode lead of cardiac pacemaker. The levels of myocardial enzymes, myoglobin (MYO), creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTNI), in patients were gradually increased after the implantation of active fixed electrode lead and reached the peak at 24 h, which were higher than those before operation (p < 0.05). The levels were decreased at 72 h with statistically significant differences. CONCLUSIONS: Female sex, age, smoking, drinking, coronary heart disease, diabetes mellitus and hyperlipidemia are independent influencing factors of pacing thresholds in a short term after the implantation of active fixed electrode lead of cardiac pacemaker. The implantation of active electrodes can raise the myocardial enzyme indexes compared with those before operation, but will fall to the preoperative levels or normal, near normal levels at 72 h after operation. The implantation of active electrodes is safe and feasible for myocardial tissues.

[The influence factors of quality-of-life in patients with thyroid-associated ophthalmopathy].

Objective: To assess the risk factors associated with decreased quality-of-life in patients with thyroid-associated ophthalmopathy (TAO). Methods: Cross-sectional study. One hundred and twelve patients with TAO and 68 controls were recruited to answer the Graves' ophthalmopathy quality-of-life questionnaire (GO-QOL) from January 2014 to April 2016. The GO-QOL included two subscales: the visual functioning and the psychosocial consequences. The differences in the GO-QOL scores between TAO patients and controls were analyzed. The influences of multiple factors on the GO-QOL scores among TAO patients were explored. Results: Among 112 TAO patients, 63 were male and 49 were female, with an average age of (45.4±13.1) years. Among 68 controls, 36 were male and 32 were female, with an average age of (39.5±10.8) years. Independent sample t test showed that TAO patients had significantly lower scores than controls in the visual functioning subscale and the psychosocial consequences subscale (55.63±29.02 vs 97.48±6.96, t=-14.58, P<0.01; 57.61±29.97 vs100±0.00, t=-14.97, P<0.01). Among TAO patients, smokers were associated with significantly lower psychological subscale scores than non-smokers (t=-2.284, P=0.024). Patients with abnormal primary position of eye scored significantly lower than those with normal alignment in functional (t=-3.979, P<0.001) and psychological subscales (t=-2.154, P=0.034) Patients with abnormal eye movement had significantly lower functional scores than those without (t=-2.975, P=0.004). One-way analysis of variance showed that higher CAS scores were significantly related to lower psychological subscale scores (F=3.178, P=0.018). Patients with upper eyelid retraction had significantly lower psychological subscale scores than those without (F=3.562, P=0.032). Pearson correlation analysis showed that age was negatively correlated with functional subscale scores (r=-0.366; P<0.01). TAO course was negatively correlated with functional (r=-0.235, P<0.05) and psychological subscale scores (r=-0.320, P<0.01). The degree of exophthalmos was negatively correlated with psychological subscale scores (r=-0.209, P<0.01). Multivariable linear regression analysis showed that only primary position of eye (P=0.013) and TAO course (P=0.007) were negatively correlated with functional subscale scores and only CAS scores (P=0.022) and TAO course (P=0.024) were negatively correlated with psychological subscale scores. Conclusion: Risk factors associated with lower quality-of-life among TAO patients included abnormal primary position of eye, higher CAS scores, and longer TAO course.(Chin J Ophthalmol,2017,53: 575-582).

[Expression of E-cadherin, N-cadherin, ß-catenin and their clinical significance in laryngeal carcinoma].

OBJECTIVE: To investigate the expression of E-cadherin(E-cad), N-cadherin(N-cad), ß-catenin(ß-cat), which are the markers of Epithelial-mesenchymal transition and analyze their relationships with the clinicopathological features and the prognosis of the laryngeal squamous cell carcinoma. METHODS: The expression levels of E-cad, N-cad, ß-cat in 76 tumor tissues and their corresponding adjacent normal laryngeal tissues were determined by immunohistochemistry method. Relationships between the proteins' expression and clinicopathological features were analyzed. Survival curves were calculated using the Kaplan-Meier method. Differences in the survival rates were analyzed by the log-rank test among different expression groups. Cox's regression model was used to examine the independent predictor of the prognosis of the laryngeal cancer. RESULTS: The expression levels of E-cad, N-cad, ß-cat in tumor tissues and adjacent normal tissues were statistically significant(P<0.001). The expression level of E-cad and ß-cat in the laryngeal carcinoma was related to lymph node metastasis, clinical pathological stage and differentiation degree (P<0.05), while N-cad expression level was associated with clinical stage and differentiation degree (P<0.05). The expression of E-cad was correlated with the expression of ß-cat (P=0.001), and the expression of N-cad was correlated with ß-cat (P=0.02), but the expression of E-cad was not correlated with N-cad. There were four subgroups of patterns of E-cad and N-cad expression: E-cad (+ )/N-cad (-), E-cad (+ ) /N-cad (+ ), E-cad (-) /N-cad (-), E-cad (-) /N-cad (+ ). The expression level of each group was related to the clinical pathological stage and differentiation degree (P<0.05). The expression level of E-cad/ß-cat was associated with lymph node metastasis, clinical pathological stage and differentiation degree (P<0.01). Log-rank analysis showed that the prognosis of negative and positive groups was statistically different (P<0.05), and the combined analysis showed that the prognosis of E-cad/N-cad or E-cad/ß-cat group was significantly different (P<0.01). Cox's regression model analysis showed that the clinical stage and ß-cat were independent predictors of the prognosis of laryngeal carcinoma. CONCLUSIONS: The low expression of E-cad, high abnormal expression of N-cad and ß-cat played an important role in the occurrence and development of laryngeal carcinoma. It can provide a reference for evaluating clinical prognosis. The clinical pathological stage and ß-cat can be used as independent predictors for the prognosis of laryngeal carcinoma.

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes.

UNLABELLED: Phosphatidylinositol-3 kinases (PI3K)-Protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway plays an important role in the synthesis and secretion of triacylglycerol. However, the mechanism of PI3K-Akt-mTOR pathway in regulating lipid metabolism of goose liver was poorly understood. The purpose of this study was to determine how PI3K-Akt-mTOR pathway regulating lipid metabolic homeostasis in goose hepatocytes. Goose primary hepatocytes were treated with different PI3K-Akt-mTOR signal inhibitors (LY294002, rapamycin and NVP-BEZ235) for 24 h. The results showed that these inhibitors evidently inhibited PI3K-Akt-mTOR downstream signaling. Meanwhile, these PI3K-Akt-mTOR inhibitors reduced intracellular lipid accumulation, decreased the mRNA expression and protein content of genes involved in the de novo fatty acid synthesis, while increased the transcriptional and protein level of key factors involved in fatty acid oxidation and very low density lipoprotein (VLDL) assembly and secretion. CONCLUSION: These findings suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes.

Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes.

BACKGROUND: Subtypes defined by hormonal receptor (HR) and HER2 status have not been well studied in inflammatory breast cancer (IBC). We characterized clinical parameters and long-term outcomes, and compared pathological complete response (pCR) rates by HR/HER2 subtype in a large IBC patient population. We also compared disease-free survival (DFS) and overall survival (OS) between IBC patients who received targeted therapies (anti-hormonal, anti-HER2) and those who did not. PATIENTS AND METHODS: We retrospectively reviewed the records of patients diagnosed with IBC and treated at MD Anderson Cancer Center from January 1989 to January 2011. Of those, 527 patients had received neoadjuvant chemotherapy and had available information on estrogen receptor (ER), progesterone receptor (PR), and HER2 status. HR status was considered positive if either ER or PR status was positive. Using the Kaplan-Meier method, we estimated median DFS and OS durations from the time of definitive surgery. Using the Cox proportional hazards regression model, we determined the effect of prognostic factors on DFS and OS. Results were compared by subtype. RESULTS: The overall pCR rate in stage III IBC was 15.2%, with the HR-positive/HER2-negative subtype showing the lowest rate (7.5%) and the HR-negative/HER2-positive subtype, the highest (30.6%). The HR-negative, HER2-negative subtype (triple-negative breast cancer, TNBC) had the worst survival rate. HR-positive disease, irrespective of HER2 status, had poor prognosis that did not differ from that of the HR-negative/HER2-positive subtype with regard to OS or DFS. Achieving pCR, no evidence of vascular invasion, non-TNBC, adjuvant hormonal therapy, and radiotherapy were associated with longer DFS and OS. CONCLUSIONS: Hormone receptor and HER2 molecular subtypes had limited predictive and prognostic power in our IBC population. All molecular subtypes of IBC had a poor prognosis. HR-positive status did not necessarily confer a good prognosis. For all IBC subtypes, novel, specific treatment strategies are needed in the neoadjuvant and adjuvant settings.

Change of selenium in environment and risk of adolescent idiopathic scoliosis: a retrospective cohort study.

OBJECTIVES: Scoliosis is the disease which has a long history over one century. However, the pathogenesis remains unclear at present. To demonstrate the effect of different selenium content in environment on the morbidity of adolescent idiopathic scoliosis (AIS). METHODS: Retrospective cohort study (follow-up from 1997 to 2009): compare the difference morbidity between high selenium group and the normal selenium group of AIS. PATIENTS: 9998 cases from three areas in China were participated in this study. There is different selenium content in these three areas. RESULTS: High selenium levels were significant associated with the AIS morbidity. While low selenium level had no significant correlation with the AIS morbidity. CONCLUSIONS: This study confirmed that high selenium content in the environment was one of risk factors for idiopathic scoliosis. We speculated that the excessive growth of the spine and the spinal cord asynchronous growth effect were key factors that high selenium content in the environment leads to scoliosis.

Statin use in primary inflammatory breast cancer: a cohort study.

BACKGROUND: Some studies have suggested that statins, which have cholesterol-lowering and anti-inflammatory properties, may have antitumor effects. Effects of statins on inflammatory breast cancer (IBC) have never been studied. METHODS: We reviewed 723 patients diagnosed with primary IBC in 1995-2011 and treated at The University of Texas MD Anderson Cancer Center. Statin users were defined as being on statins at the initial evaluation. Based on Ahern et al's statin classification (JNCI, 2011), clinical outcomes were compared by statin use and type (weakly lipophilic to hydrophilic (H-statin) vs lipophilic statins (L-statin)). We used the Kaplan-Meier method to estimate the median progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS), and a Cox proportional hazards regression model to test the statistical significance of potential prognostic factors. RESULTS: In the multivariable Cox model, H-statins were associated with significantly improved PFS compared with no statin (hazard ratio=0.49; 95% confidence interval=0.28-0.84; P<0.01); OS and DSS P-values were 0.80 and 0.85, respectively. For L-statins vs no statin, P-values for PFS, DSS, and OS were 0.81, 0.4, and 0.74, respectively. CONCLUSION: H-statins were associated with significantly improved PFS. A prospective randomised study evaluating the survival benefits of statins in primary IBC is warranted.

The impact of phosphorylated AMP-activated protein kinase expression on lung cancer survival.

BACKGROUND: The aim of this study is to investigate the prognostic role of phosphorylated AMP-activated protein kinase (pAMPK) in surgically resected non-small-cell lung cancer (NSCLC). METHODS: Immunohistochemical staining of pAMPK was carried out on tissue microarrays containing 463 samples obtained from patients with NSCLC and correlated with clinicopathological characteristics and survival. RESULTS: pAMPK expression levels were significantly higher in never smokers versus former smokers versus current smokers (P=0.045). A positive pAMPK expression was associated with increased overall survival (OS) and recurrence-free survival (RFS) (P=0.0009 and P=0.0007, respectively). OS and RFS were statistically superior in pAMPK-positive than in pAMPK-negative patients with adenocarcinoma (ADC; median OS: 5.6 and 4.2 years, respectively, P=0.0001; median RFS: 5.0 and 2.4 years, respectively, P=0.001), whereas they were similar in those patients with squamous cell carcinoma. Multivariate analysis confirmed that pAMPK positivity was associated with OS [hazard ratio (HR)=0.574, 95% confidence interval (CI) 0.418-0.789, P=0.0006) and RFS (HR=0.608, 95% CI 0.459-0.807, and P=0.0006), independent of clinical covariates. CONCLUSIONS: High pAMPK expression levels are associated with increased survival in patients with NSCLC, especially those with ADC. Our results support further evaluation of AMP-activated protein kinase as a potential prognostic and therapeutic target for lung cancer.

Isolation, sequence identification and expression profile of three novel genes Rab2A, Rab3A and Rab7A from Black-boned sheep (Ovis aries).

Complete coding sequences of three Black-boned sheep (Ovis aries) genes Rab2A, Rab3A and Rab7A were amplified using reverse transcription polymerase chain reaction (RT-PCR) based on the conserved sequence information of cattle or other mammals known to be highly homologous to sheep ESTs. The Black-boned sheep Rab2A gene encodes a protein of 226 amino acids which contains the conserved putative RabL2 domain and is highly homologous to the Rab2A proteins of seven other species--cattle (96%), human (83%), Sumatran orangutan (82%), rat (81%), mouse (80%), African clawed frog (72%) and zebrafish (71%). The Black-boned sheep Rab3A gene encodes a protein of 220 amino acids that contains the conserved putative Rab3 domain and is very similar to the Rab3A proteins of four species--cattle (99%), African clawed frog (99%), Western clawed frog (98%) and zebrafish (95%). And the Black-boned sheep Rab7A gene encodes a protein of 207 amino acids that contains the conserved putative Rab7 domain and has high homology with the Rab7A proteins of six other species--human (99%), dog (99%), Sumatran orangutan (99%), zebrafish (97%), rabbit (97%) and African clawed frog (96%). Analysis of the phylogenetic tree has demonstrated that the Black-boned sheep Rab2A, Rab3A and Rab7A proteins share a common ancestor and the tissue expression analysis has shown that the corresponding genes are expressed in a range of tissues including leg muscle, kidney, skin, longissimus dorsi muscle, spleen, heart and liver. Our experiment is the first to provide the primary foundation for a further insight into these three sheep genes.

Histopathological and biochemical changes following fat embolism with administration of corn oil micelles: a new animal model for fat embolism syndrome.

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A(2), nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome.