The IκB kinase (IKK)/NF-κB pathway has been shown to be a major regulator in cell survival. However, the mechanisms through which IKK mediates cell death are not clear. In this study, we showed that IKK-β contributed to hydrogen peroxide (H2O2)-induced cell death independent of the NF-κB pathway. Our results demonstrated that the pro-death function of IKK-β under oxidative stress was mediated by p85 S6K1 (S6 kinase 1), but not p70 S6K1 through a rapamycin-insensitive and mammalian target of rapamycin complex 1 kinase-independent mechanism. We found that IKK-β associated with p85, but not p70 S6K1, which was required for H2O2-induced activation of p85 S6K1. IKK-β and p85 S6K1 contributed to H2O2-induced phosphorylation of Mdm2 (S166) and p53 accumulation. p85 S6K1 is critical for IKK-β-mediated cell death. Thus, these findings established a novel oxidative stress-responsive pathway that involves IKK-β, p85 S6K1 and Mdm2, which is response for H2O2-induced cell death. Our results have important implications for IKK-β and p85 S6K1 as potential targets for the prevention of diseases involved in oxidative stress-induced aberrant cell death.
IKK-β; hydrogen peroxide; S6K1; mammalian target of rapamycin
Regulator of Cullins-1 (ROC1) or RING box protein-1 (RBX1) is an essential RING component of Cullin-RING ligase (CRL). Our previous studies showed that ROC1 is required for the growth of several cancer cell lines while ROC1 siRNA silencing inactivates CRL, leading to cell cycle arrest, cell senescence and/or apoptosis. However, it is completely unknown whether ROC1 knockdown triggers autophagic response by inactivating CRL. Moreover, the role of ROC1 in liver cancer remains elusive. In this study, we reported that ROC1 knockdown significantly inhibited the growth of liver cancer cells by sequentially and independently inducing autophagy and p21-dependent cell senescence. Mechanism analysis revealed that ROC1 silencing triggered autophagy by inhibition of mammalian target of rapamycin (mTOR) activity due to accumulation of mTOR-inhibitory protein Deptor, a substrate of CRL. Consistently, Deptor knockdown significantly blocked autophagy response upon ROC1 silencing. Biologically, autophagy response upon ROC1 silencing was a survival signal, and blockage of autophagy pathway sensitized cancer cells to apoptosis. Finally, we demonstrated that ROC1 was overexpressed in hepatocellular carcinomas, which is associated with poor prognosis of liver cancer patients. These findings suggest that ROC1 is an appealing drug target for liver cancer and provide a proof-of-concept evidence for a novel drug combination of ROC1 inhibitor and an autophagy inhibitor for effective treatment of liver cancer by enhancing apoptosis.
ROC1; Cullin-RING ligase; autophagy; senescence; Deptor
The increased risk of gastrointestinal (GI) cancers after Hodgkin's lymphoma (HL) is well established. However, no large population-based study has described the actuarial survival after subsequent GI cancers in HL survivors (HL-GI).
Patients and methods
For 209 patients with HL-GI cancers (105 colon, 35 stomach, 30 pancreas, 21 rectum, and 18 esophagus) and 484 165 patients with first primary GI cancers (GI-1), actuarial survival was compared, accounting for age, gender, race, GI cancer stage, radiation for HL, and other variables.
Though survival of HL patients who developed localized stage colon cancer was similar to that of the GI-1 group, overall survival (OS) of HL patients with regional or distant stage colon cancer was reduced [hazard ratio, (HR) = 1.46, P = 0.01]. The HL survivors with regional or distant stage colon cancer in the transverse segment had an especially high risk of mortality (HR: 2.7, P = 0.001 for OS). For localized stomach cancer, OS was inferior among HL survivors (HR = 3.46, P = 0.006).
The HL patients who develop GI cancer experience significantly reduced survival compared with patients with a first primary GI cancer. Further research is needed to explain the inferior survival of HL patients and to define selection criteria for cancer screening in HL survivors.
cancer survivorship; gastrointestinal cancers; Hodgkin lymphoma; second cancers; SEER
Dietary glycemic index (GI) and glycemic load (GL) typically have a positive relationship with obesity and diabetes, which are risk factors for liver cancer. However, studies on their association with liver cancer have yielded inconsistent results. Therefore, we assessed the association of GI, GL, and carbohydrates with liver cancer risk.
Patients and methods
A total of 72 966 women and 60 207 men from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) were included for analysis. Food frequency questionnaire (FFQ) data were used to calculate daily dietary GI, GL, and carbohydrate intake. These values were energy adjusted and categorized into quintiles. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with adjustment for potential confounders.
After a median follow-up time of 11.2 years for the SWHS and 5.3 years for the SMHS, 139 and 208 incident liver cancer cases were identified in the SWHS and SMHS, respectively. In multivariable Cox regression models, no statistically significant trends by quintile of GI, GL, or carbohydrate intake were observed. Stratification by chronic liver disease/hepatitis, diabetes, or body mass index (BMI) did not alter the findings.
There is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population.
Chinese men and women; cohort study; diet; glycemic index; glycemic load; primary liver cancer
To determine normative values and associations of retinal nerve fiber layer (RNFL) and optic disc parameters in normal eyes measured by spectral domain optical coherence tomography (OCT).
In a population-based setting, 1521 young adults were examined as part of the Sydney Adolescent Vascular and Eye Study (SAVES). Their mean age was 17.3±0.6 years. RNFL and optic disc parameter measurements were made using Cirrus HD-OCT 4000.
The average RNFL was found to be 99.4±9.6 μm. RNFL thickness was least for the temporal quadrant (69.9±11.2 μm), followed by the nasal (74.3±12.8 μm), superior (124.7±15.7 μm) and inferior (128.8±17.1 μm) quadrants. The mean disc area in this population was 1.98±0.38 mm2 with a mean rim area of 1.50±0.30 mm2 and a mean cup/disc ratio of 0.44±0.18. Multivariate-adjusted RNFL thickness was marginally greater in East Asian than in white participants (100.1 μm vs 99.5 μm; P=0.0005). The RNFL was thinner with greater axial length (P<0.0001), less positive spherical equivalent refractions (P<0.0001), smaller disc area and rim area (P<0.0001).
This study documents normative values for the RNFL and optic disc measured using Cirrus HD-OCT in young adults. The values and associations reported in this study can inform clinicians on the normal variation in RNFL and optic disc parameters.
retinal nerve fiber layer; optic disc; optical coherence tomography; Sydney Childhood Eye Study
Notch signaling inhibits differentiation of endocrine cells in the pancreas and intestine. In a number of cases, the observed inhibition occurred with Notch activation in multipotential cells, prior to the initiation of endocrine differentiation. It has not been established how direct activation of Notch in endocrine precursor cells affects their subsequent cell fate. Using conditional activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the effects of Notch in both organs, on cell fate of early endocrine precursors and maturing endocrine-restricted cells respectively. Notch did not preclude the differentiation of a limited number of endocrine cells in either organ when activated in Ngn3+ precursor cells. In addition, in the pancreas most Ngn3+ cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3+ cells, Notch favored enterocyte and goblet cell fates, while selecting against endocrine and Paneth cell differentiation. A small fraction of NeuroD1+ cells in the pancreas retain plasticity to respond to Notch, giving rise to intraislet ductules as well as cells with no detectable pancreatic lineage markers that appear to have limited ultrastructural features of both endocrine and duct cells. These results suggest that Notch directly regulates cell fate decisions in multipotential early endocrine precursor cells. Some maturing endocrine-restricted NeuroD1+ cells in the pancreas switch to the duct lineage in response to Notch, indicating previously unappreciated plasticity at such a late stage of endocrine differentiation.
Low 25-hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident non-spine fractures studied in a case-cohort design. “Abnormal” was defined as lowest quartile for VitD (<20 ng/ml), bioavailable testosterone (BioT, <163 ng/dl), and bioavailable estradiol (BioE, <11 pg/ml); and highest quartile for SHBG (>59 nM).
Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality, and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate-adjusted hazard ratio (95% CI) for incident non-spine fracture during 4.6 yr median follow-up was 1.2 (0.8–1.8) for low VitD alone; 1.3 (0.9–1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1–2.5) for low BioE/high SHBG plus low VitD.
In summary, adverse skeletal effects of low sex steroid levels were most pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health.
bone loss; fracture; older men; sex hormones; vitamin
The objective of this study was to pool the lymph node metastasis rate (LNMR) in patients with thoracic oesophageal cancer (TOC) and to determine which node level should be included when undergoing radiation therapy.
Qualified studies were identified on Medline, Embase, CBM and the Cochrane Library through to the end of April 2011. Pooled estimates of LNMR were obtained through a random-effect model. Possible effect modifiers which might lead to the statistical heterogeneity were identified through meta-regression, and further subgroup analyses of factors influencing LNMR were performed.
45 observational studies with a total of 18 415 patients were included in the meta-analysis. The pooled estimates of LNMR in upper, middle and lower TOC were 30.7%, 16.8% and 11.0% cervical, 42.0%, 21.1% and 10.5% upper mediastinal, 12.9%, 28.1% and 19.6% middle mediastinal, 2.6%, 7.8% and 23.0% lower mediastinal, and 9%, 21.4% and 39.9% abdominal, respectively. Lymph node metastasis most frequently happened to paratracheal, paraoesophageal, perigastric 106recR and station 7. The most obvious difference (≥15%) of LNMR between two-field and three-field lymphatic dissection occurred in cervical, paratracheal, 106recR and 108.
Through the meta-analysis, more useful information was obtained about clinical target volume (CTV) delineation of TOC patients treated with radiotherapy. However, our study is predominantly a description of squamous carcinoma and the results may not be valid for adenocarcinoma.
Few data are available about intakes and food sources of trans-fatty acids (TFAs) or their associations with cardiometabolic outcomes in Asian people who consume a prudent diet but are experiencing rapid nutritional transitions. We aimed to investigate the relationships between TFA biomarkers and type 2 diabetes and cardiovascular risk factors in Chinese individuals.
Erythrocyte fatty acids were measured by gas chromatography among 3,107 men and women (50–70 years) recruited from urban and rural areas in Beijing and Shanghai, China.
Total trans-18:1 and two trans-18:2 isomers were detected and accounted for 0.37% of the total fatty acids in the erythrocytes. Concentrations of TFAs were higher in women than men, and in urban than rural residents. Of the TFAs, trans-18:1, but not trans-18:2, showed a modest association with dairy consumption (β=0.27), but not with other foods. After adjustment for BMI, social-demographic, lifestyle and dietary factors and other TFAs, erythrocyte trans-18:1 was shown to be associated with a lower risk of type 2 diabetes (OR comparing extreme quartiles=0.68, 95% CI=0.48, 0.97, ptrend=0.02), as well as 20–50% lower odds of central obesity, dyslipidaemia, hyperglycemia, insulin resistance and chronic inflammation. In contrast, trans-18:2 fatty acids were positively associated with high triacylglycerol (ptrend<0.001) and LDL-cholesterol (ptrend=0.03) levels, but not with diabetes and other cardiometabolic risk factors.
Among middle-aged and older Chinese individuals with overall low erythrocyte TFAs levels, trans-18:1 might serve as a marker of dairy intake. Higher trans-18:1 levels were associated with a lower risk of type 2 diabetes, whereas higher trans-18:2 levels were associated with dyslipidaemia.
Biomarkers; Diet; Dyslipidaemia; trans-Fatty acids; Type 2 diabetes
In a previous study, we elucidated the specific microRNA (miRNA) profile of hepatic differentiation. In this study, we aimed to clarify the instructive role of six overexpressed miRNAs (miR-1246, miR-1290, miR-148a, miR-30a, miR-424 and miR-542-5p) during hepatic differentiation of human umbilical cord lining-derived mesenchymal stem cells (hMSCs) and to test whether overexpression of any of these miRNAs is sufficient to induce differentiation of the hMSCs into hepatocyte-like cells. Before hepatic differentiation, hMSCs were infected with a lentivirus containing a miRNA inhibitor sequence. We found that downregulation of any one of the six hepatic differentiation-specific miRNAs can inhibit HGF-induced hepatic differentiation including albumin expression and LDL uptake. Although overexpression of any one of the six miRNAs alone or liver-enriched miR-122 cannot initiate hepatic differentiation, ectopic overexpression of seven miRNAs (miR-1246, miR-1290, miR-148a, miR-30a, miR-424, miR-542-5p and miR-122) together can stimulate hMSC conversion into functionally mature induced hepatocytes (iHep). Additionally, after transplantation of the iHep cells into mice with CCL4-induced liver injury, we found that iHep not only can improve liver function but it also can restore injured livers. The findings from this study indicate that miRNAs have the capability of directly converting hMSCs to a hepatocyte phenotype in vitro.
miRNA; mesenchymal stem cells; hepatic differentiation; hepatocytes
Apoptosis resistance is a hurdle for cancer treatment. HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 depletion can sensitize cancer cells to extrinsic apoptotic stimuli. In addition, HECTD3 inhibits TNF-related apoptosis-inducing ligand (TRAIL)-induced caspase-8 cleavage in an E3 ligase activity-dependent manner. Mutation of the caspase-8 ubiquitination site at K215 abolishes the HECTD3 protection from TRAIL-induced cleavage. Finally, HECTD3 is frequently overexpressed in breast carcinomas. These findings suggest that caspase-8 ubiquitination by HECTD3 confers cancer cell survival.
ubiquitination; apoptosis; breast cancer; HECTD3; caspase-8
In the present study, the effects of tanshinone IIA (TSN) on the prevention of left ventricular hypertrophy (LVH) and apoptotic processes were observed in spontaneously hypertensive rats (SHRs). A total of 18 SHRs (age, 8 weeks) were randomly divided into three groups. The SHRs in the control group (group S8) were sacrificed at week 8 of the experiment. The SHRs in the treatment group (group D18) and the placebo group (group S18) were injected with TSN and distilled water (1 ml/kg body weight/day), respectively, for 10 weeks, commencing at week 8, and were subsequently sacrificed at week 18. The systolic blood pressure (SBP) and left ventricular mass index (LVMI) were determined. Using hematoxylin and eosin and van Gieson staining, together with immunohistological methods, cardiomyocyte size and diameter, collagen volume fraction (CVF) and perivascular circumferential area (PVCA) were measured. Evaluation of Bcl-2, Bax and p53 expression levels for apoptosis analysis was performed using western blotting. It was observed that the SBP, LVMI, cardiomyocyte size and diameter, CVF, PCVA and cardiomyocyte apoptosis index (Bax and p53 expression) were increased significantly in group S18 compared with group S8. However, Bcl-2 expression levels were decreased in group S18 compared with group S8. The administration of TSN in group D18 resulted in higher Bcl-2 expression levels and significantly decreased LVMI, cardiomyocyte size and diameter, CVF, PCVA, Bax and p53 expression levels compared with group S18. LVH and apoptosis of the cardiac tissues increased with the increasing age of the SHRs. TSN may inhibit the development of LVH and decrease the level of apoptosis in SHRs, possibly via the upregulation of Bcl-2 and the downregulation of Bax and p53 expression.
left ventricular hypertrophy; apoptosis; tanshinone IIA; p53; Bcl-2; Bax
Music is a powerful medium capable of eliciting a broad range of emotions. Although the relationship between language and music is well documented, relatively little is known about the effects of lyrics and the voice on the emotional processing of music and on listeners' preferences. In the present study, we investigated the effects of vocals in music on participants' perceived valence and arousal in songs. Participants (N = 50) made valence and arousal ratings for familiar songs that were presented with and without the voice. We observed robust effects of vocal content on perceived arousal. Furthermore, we found that the effect of the voice on enhancing arousal ratings is independent of familiarity of the song and differs across genders and age: females were more influenced by vocals than males; furthermore these gender effects were enhanced among older adults. Results highlight the effects of gender and aging in emotion perception and are discussed in terms of the social roles of music.
emotion; music; arousal; perception; gender; aging
Asymmetric dimethylarginine (ADMA) is synthesized by protein arginine methyltransferases during methylation of protein arginine residues and released into blood upon proteolysis. Higher concentrations of ADMA in blood have been observed in patients with metabolic diseases and certain cancers. However, the role of ADMA in colon cancer has not been well investigated. ADMA serum levels in human patients diagnosed with colon cancer were found to be higher than those present in healthy subjects. ADMA treatment of LoVo cells, a human colon adenocarcinoma cell line, attenuated serum starvation-induced apoptosis and suppressed the activation of the Fas (APO-1/CD95)/JNK (SAPK) (c-Jun N terminal protein kinase/stress-activated protein kinase)pathway. ADMA also suppressed the activation of JNK triggered by death receptor ligand anti-Fas mAb and exogenous C2-ceramide. Moreover, we demonstrated that ADMA pretreatment protected LoVo cells from doxorubicin hydrochloride-induced cell death and activation of the Fas/JNK pathway. In summary, our results suggest that the elevated ADMA in colon cancer patients may contribute to the blocking of apoptosis of cancer cells in response to stress and chemotherapy.
ADMA; colon cancer; apoptosis; Fas; JNK; chemotherapy
The presence of circulating tumor cells (CTCs) in peripheral blood is associated with metastasis and prognosis in hepatocellular carcinoma (HCC) patients. The epithelial–mesenchymal transition (EMT) has a pivotal role in tumor invasion and dissemination. To identify more sensitive biomarkers for evaluating metastasis and prognosis, we investigated the expression of EMT markers, including vimentin, twist, ZEB1, ZEB2, snail, slug and E-cadherin in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues. After isolating viable CTCs from the peripheral blood of HCC patients using asialoglycoprotein receptors (ASGPRs), the CTCs were identified with immunofluorescence staining. CTCs were detected in the peripheral blood obtained from 46 of 60 (76.7%) HCC patients. Triple-immunofluorescence staining showed that twist and vimentin expression could be detected in CTCs obtained from 39 (84.8%) and 37 (80.4%) of the 46 patients, respectively. The expression of both twist and vimentin in CTCs was significantly correlated with portal vein tumor thrombus. Coexpression of twist and vimentin in CTCs could be detected in 32 (69.6%) of the 46 patients and was highly correlated with portal vein tumor thrombus, TNM classification and tumor size. Quantitative fluorescence western blot analysis revealed that the expression levels of E-cadherin, vimentin and twist in HCC tumors were significantly associated with the positivity of isolated CTCs (P=0.013, P=0.012, P=0.009, respectively). However, there was no significant difference in ZEB1, ZEB2, snail and slug expression levels in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues across samples with regard to the clinicopathological parameters. Our results demonstrate that the EMT has a role in promoting the blood-borne dissemination of primary HCC cells, and the twist and vimentin expression levels in CTCs could serve as promising biomarkers for evaluating metastasis and prognosis in HCC patients.
circulating tumor cells; epithelial–mesenchymal transition; hepatocellular carcinoma; metastasis; biomarkers
Yme1L is an AAA protease that is embedded in the mitochondrial inner membrane with its catalytic domain facing the mitochondrial inner-membrane space. However, how Yme1L regulates mammalian mitochondrial function is still obscure. We find that endogenous Yme1L locates at punctate structures of mitochondria, and that loss of Yme1L in mouse embryonic fibroblast (MEF) cells results in mitochondrial fragmentation and leads to significant increased ‘kiss-and-run' type of mitochondrial fusion; however, Yme1L knockdown (shYme1L (short hairpin-mediated RNA interference of Yme1L)) cells still remain normal mitochondrial fusion although shYme1L mitochondria have a little bit less fusion and fission rates, and the shYme1L-induced fragmentation is due to a little bit more mitochondrial fission than fusion in cells. Furthermore, shYme1L-induced mitochondrial fragmentation is independent on optic atrophy 1 (OPA1) S1 or S2 processing, and shYme1L results in the stabilization of OPA1 long form (L-OPA1); in addition, the exogenous expression of OPA1 or L-OPA1 facilitates the shYme1L-induced mitochondrial fragmentation, thus this fragmentation induced by shYme1L appears to be associated with L-OPA1's stability. ShYme1L also causes a slight increase of mitochondrial dynamics proteins of 49 kDa and mitochondrial fission factor (Mff), which recruit mitochondrial key fission factor dynamin-related protein 1 (Drp1) into mitochondria in MEF cells, and loss of Drp1 or Mff inhibits the shYme1L-induced mitochondrial fragmentation. In addition, there is interaction between SLP-2 with Yme1L and shYme1L cells retain stress-induced mitochondrial hyperfusion. Taken together, our results clarify how Yme1L regulates mitochondrial morphology.
Yme1L; OPA1; mitochondrial 'kiss-and-run'
Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to induce apoptosis in some types of cells. However, the underlying mechanisms remain largely unclear. Using a DNA microarray analysis, we found that the expression of many genes was downregulated upon treatment with compound C. Importantly, compound C caused transcriptional repression with the induction of p53, a well-known marker of transcriptional stress response, in several cancer cell lines. Compound C did not induce the phosphorylation of p53 but dramatically increased the protein level of p53 similar to some other transcriptional inhibitors, including 5,6-dichloro-1-β-D-ribobenzimidazole (DRB). Consistent with previous reports, we found that compound C initiated apoptotic death of cancer cells in an AMPK-independent manner. Similar to DRB and actinomycin D (ActD), two classic transcription inhibitors, compound C not only resulted in the loss of Bcl-2 and Bcl-xl protein but also induced the phosphorylation of eukaryotic initiation factor-alpha (eIF2α) on Ser51. Hence, the phosphorylation of eIF2α might be a novel marker of transcriptional inhibition. It is noteworthy that compound C-mediated apoptosis of cancer cells is correlated with decreased expression of Bcl-2 and Bcl-xl and the phosphorylation of eIF2α on Ser51. Remarkably, compound C exhibits potent anticancer activities in vivo. Taken together, our data suggest that compound C may be an attractive candidate for anticancer drug development.
compound C; transcriptional inhibition; apoptosis; cancer
This study was conducted to evaluate the apparent metabolizable energy (AME) and true metabolizable energy (TME) contents in 30 sources of corn distillers dried grains with solubles (DDGS) in adult roosters, and establish the prediction equations to estimate the AME and TME value based on its chemical composition and color score.
Twenty-eight sources of corn DDGS made from several processing plants in 11 provinces of China and others imported from the United States. DDGS were analyzed for their metabolizable energy (ME) contents, measured for color score and chemical composition (crude protein, crude fat, ash, neutral detergent fiber, acid detergent fiber), to predict the equation of ME in DDGS. A precision-fed rooster assay was used, each DDGS sample was tube fed (50 g) to adult roosters. The experiment was conducted as a randomized incomplete block design with 3 periods. Ninety-five adult roosters were used in each period, with 90 being fed the DDGS samples and 5 being fasted to estimate basal endogenous energy losses.
Results showed that the AME ranged from 5.93 to 12.19 MJ/kg, TME ranged from 7.28 to 13.54 MJ/kg. Correlations were found between ME and ash content (-0.64, P < 0.01) and between ME and yellowness score (0.39, P < 0.05) of the DDGS samples. Furthermore, the best-fit regression equation for AME content of DDGS based on chemical composition and color score was AME = 6.57111 + 0.51475 GE - 0.10003 NDF + 0.13380 ADF + 0.07057 fat - 0.57029 ash - 0.02437 L (R2 = 0.70). The best-fit regression equation for TME content of DDGS was TME = 7.92283 + 0.51475 GE - 0.10003 NDF + 0.13380 ADF + 0.07057 fat - 0.57029 ash - 0.02437 L (R2 = 0.70).
This experiment suggested that measuring the chemical composition and color score of a corn DDGS sample may provide a quality parameter for identifying corn DDGS sources energy digestibility and metabolizable energy content.
Metabolizable energy; Distillers dried grains with solubles; Rooster; Predictive equation
Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3–5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis.
Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010–January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May–December 2011).
Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage.
Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.
paracentesis; ovarian cancer; PleureX
The quantitative parameters in the contrast-enhanced ultrasonography time–intensity
curve of hepatocellular carcinoma (HCC) were studied to explore
their possible implication for histological grading of HCC.
A total of 130 HCC patients (115 males and 15 females; age: 48.13±11.00
years) were studied using contrast-enhanced ultrasonography time–intensity
curve and histological pathology. The quantification software Sonoliver® (TomTec
Imaging Systems, Unterschleissheim, Germany) was applied to derive time–intensity
curves of regions of interest in the interior of HCCs and in reference. Quantitative
parameters of 115 patients were successfully obtained, including maximum of
intensity (IMAX), rise time (RT), time to peak (TTP),
rise slope (RS) and washout time (WT). Histological grading
of HCC was performed using haematoxylin–eosin staining, and monoclonal
antibodies specific for smooth muscle actin were used to observe unpaired
There were significant differences among WTs in the three differentiated
HCC groups (p<0.05). However, there were no
significant differences among RT, TTP, RS and IMAX in the differentiated HCC
groups. Moreover, the number of UAs in the differentiated HCC groups showed
no statistical significance.
WT plays an important role in predicting well, moderately and poorly differentiated
Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key factor in apoptosis and autophagy of vascular endothelial cells (VECs), and involved in atherosclerosis in apolipoprotein E−/− (apoE−/−) mice. But the endogenous regulators of PC-PLC are not known. We recently found a small chemical molecule (6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine, ABO) that could inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis and promote autophagy in VECs, and further identified ABO as an inhibitor of annexin A7 (ANXA7) GTPase. Based on these findings, we hypothesize that ANXA7 is an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO may inhibit atherosclerosis in apoE−/− mice. In this study, we tested our hypothesis. The results showed that ABO suppressed oxLDL-induced increase of PC-PLC level and activity and promoted the co-localization of ANXA7 and PC-PLC in VECs. The experiments of ANXA7 knockdown and overexpression demonstrated that the action of ABO was ANXA7-dependent in cultured VECs. To investigate the relation of ANXA7 with PC-PLC in atherosclerosis, apoE−/− mice fed with a western diet were treated with 50 or 100 mg/kg/day ABO. The results showed that ABO decreased PC-PLC levels in the mouse aortic endothelium and PC-PLC activity in serum, and enhanced the protein levels of ANXA7 in the mouse aortic endothelium. Furthermore, both dosages of ABO significantly enhanced autophagy and reduced apoptosis in the mouse aortic endothelium. As a result, ABO significantly reduced atherosclerotic plaque area and effectively preserved a stable plaques phenotype, including reduced lipid deposition and pro-inflammatory macrophages, increased anti-inflammatory macrophages, collagen content and smooth muscle cells, and less cell death in the plaques. In conclusion, ANXA7 was an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO inhibited atherosclerosis in apoE−/− mice.
apoptosis; autophagy; PC-PLC; ANXA7; ABO; atherosclerosis
We report a case of an osteochondroma in the form of an anomalous bifid distal ulna following mal-union of an epiphyseal injury. There has been no previous case of this reported in the medical literature.
PRESENTATION OF CASE
A 19-year-old man presented with wrist stiffness and complete loss of pronation and supination twelve months after having undergone open reduction and internal fixation for a volarly displaced distal radius fracture. Further investigation with a CT scan showed a bifid distal ulna. As this was not present on plain radiographs one year prior, it was proposed that this was an osteochrondromatous growth caused by injury to the distal ulnar epiphysis. An operation was performed to excise one of the distal ulna heads, and reconstruct the TFCC to allow improved rotational movements. At one year follow-up, the patient has made an almost full recovery without complication.
We postulate that the patient sustained an occult physeal injury resulting in an osteochondromatous lesion that grew towards the joint effectively forming a second ulna head.
This is a unique case of the development of a bifid distal ulna due to physeal injury one year prior. Such a lesion has not previously been described in the distal ulna.
Ulna; Fracture; Bifid; Deformity; Osteochondroma
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. The risk of pregnancy and neonatal complications in women with PCOS is debatable. In order to determine the risk of pregnancy and neonatal complications, evidence regarding these risks was examined.
Literature searches were performed in the electronic databases MEDLINE, EMBASE, and CENTRAL based on the established strategy and eligible tries were included according to inclusion and exclusion criteria. A systematic literature review looking at rates of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia, premature delivery, neonatal birth weight, caesarean section and admission to a neonatal intensive care unit (NICU) was conducted in women with PCOS. Pregnancy outcomes between women with PCOS versus controls were included. Sensitivity analyses were performed to determine the reliability of the available evidence and to validate the results. The study was performed with the approval of the ethics committee of the First Affiliated Hospital of Guangxi Medical University.
A total of 27studies, involving 4982 women with PCOS and 119692 controls were eligible for the meta-analysis. Women with PCOS demonstrated a significantly higher risk of developing GDM (OR3.43; 95% CI: 2.49–4.74), PIH (OR3.43; 95% CI: 2.49–4.74), preeclampsia (OR2.17; 95% CI: 1.91–2.46), preterm birth (OR1.93; 95%CI: 1.45–2.57), caesarean section (OR 1.74; 95% CI: 1.38–2.11) compared to controls. Their babies had a marginally significant lower birth weight (WMD −0.11g; 95%CI: -0.19 – -0.03), and higher risk of admission to NICU (OR 2.32; 95% CI: 1.40–3.85) compared to controls.
Women with PCOS have increased risk of adverse pregnancy and neonatal complications. It is necessary to establish guidelines for supervision during pregnancy and parturition to prevent these complications.
Polycystic ovary syndrome; Pregnancy and neonatal complications; Meta-analysis