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Background: This study aimed to investigate the raltitrexed loading method, compatible stability with contrast agent, release profiles, and morphological properties of CalliSpheres, DC Bead, and He...

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16- NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16- and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

Gastric cancer (GC) is the second leading cause of cancer deaths around the world. Chemoresistance is an important reason for poor prognosis of GC. Saikosaponin D (SSD) is a natural constituent from Radix Bupleuri and exhibits various activities including antitumors. This study investigated the effects and the mechanisms of SSD on cisplatin (cis-diamminedichloroplatinum, DDP) sensitivity of GC cells. Findings suggested that SSD could promote the inhibitory effect of DDP on proliferation and invasion and increase DDP-induced apoptosis in SGC-7901 and DDP-resistant cell line SGC-7901/DDP. We further identified that SSD increased levels of LC3 B and cleaved caspase 3 and decreased levels of p62, IKK β, p-IκB α, and NF-κB p65, suggesting that SSD might inhibit the IKK β/NF-κB pathway and induce both cell autophagy and apoptosis in SGC-7901 and SGC-7901/DDP. A further study indicated that SSD enhanced the effect of DDP-induced cleaved caspase 3 level rise and NF-κB pathway suppression, especially in SGC-7901/DDP cells. Conclusively, SSD enhanced DDP sensitivity of GC cells; the potential molecular mechanisms were that SSD-induced apoptosis and autophagy and inhibited the IKK β/NF-κB pathway in GC cells. These findings suggested that SSD might contribute to overcoming DDP resistance in GC treatment.

Purpose To evaluate the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) creation for the prevention of gastric variceal rebleeding in patients with hepatocellular carcinoma (HCC). Materials and Methods This multicenter retrospective study included 126 cirrhotic patients (mean age, 54.1 ± 10.2 years; 110 men) with HCC who underwent TIPS creation for the prevention of gastric variceal rebleeding. Of these, 110 (87.3%) patients had gastroesophageal varices and 16 (12.7%) patients had isolated gastric varices. Thirty-five (27.8%) patients had portal vein tumor thrombus. Results TIPS creation was technically successful in 124 (98.4%) patients. Rebleeding occurred in 26 (20.6%) patients during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 98.3% ± 1.2% and 81.2% ± 3.9%, respectively. Forty-nine (38.8%) patients died during the follow-up period. The 6-week and 1-year actuarial probabilities of survival were 98.4 ± 1.1% and 65.6 ± 4.4%, respectively. Two (1.6%) patients had major procedure-related complications, including acute liver failure (n = 1) and intra-abdominal bleeding (n = 1). Thirty-three (26.2%) patients had at least 1 episode of overt hepatic encephalopathy during the follow-up period. Shunt dysfunction occurred in 15 (11.9%) patients after a median follow-up time of 11.4 months (range, 1.4–41.3 months). Lung metastasis occurred in 3 (2.4%) patients, 3.9–32.9 months after TIPS creation. Conclusions TIPS creation may be effective and safe for the prevention of gastric variceal rebleeding in patients with HCC.

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. High AAMDC expression is associated with sensitization to dactolisib and everolimus, and these PI3K-mTOR inhibitors exhibit synergistic interactions with anti-estrogens in IntClust2 models. Ectopic AAMDC expression is sufficient to activate AKT signaling, resulting in estrogen-independent tumor growth. Thus, AAMDC-overexpressing tumors may be sensitive to PI3K-mTORC1 blockers in combination with anti-estrogens. Lastly, we provide evidence that AAMDC can interact with the RabGTPase-activating protein RabGAP1L, and that AAMDC, RabGAP1L, and Rab7a colocalize in endolysosomes. The discovery of the RabGAP1L-AAMDC assembly platform provides insights for the design of selective blockers to target malignancies having the AAMDC amplification., Adipogenesis associated Mth938 Domain Containing gene (AAMDC) is frequently amplified in the IntClus2 subgroup of ER + breast cancer. Here, the authors show that AAMDC drives tumourigenesis through activating PI3K-AKT-mTOR pathway for metabolic reprogramming.

The aim of the present study was to investigate the predilection position of hemorrhagic stigmata (HS) in patients with esophageal variceal hemorrhage and provide guidance on endoscopic therapy for esophageal varices. The clinical characteristics, particularly the endoscopic manifestations of HS, in the patients who presented with gastroesophageal variceal hemorrhage and cirrhosis between January 2003 and December 2013 at our hospital were summarized and patients were grouped according to the distance of the lesion site to incisors at 35–40 and ~30 cm. The association between the location of HS and active hemorrhage was assessed. The location of hemorrhage and HS at 35–40 cm from the incisors was more common in esophageal varices patients, followed by the location at ~30 cm from the incisors (P

Aberrant expression of miRNAs is involved in several carcinogenic processes, including tumor growth, metastasis and angiogenesis. The aim of this study was to determine the role of miR-218 in gastric cancer angiogenesis. In situ hybridization was performed on a set of tissue microarray samples to assess the difference in miR-218 expression in vessels between tumor tissues and normal gastric mucosa. In vitro, ectopic expression of miR-218 disturbed the tubular structure and inhibited the migration of endothelial cells. Motility and tube formation were rescued when miR-218 was downregulated. Moreover, miR-218 suppressed endothelial cell sprouting in a fibrin bead sprouting assay. Subsequently, we identified ROBO1 as a target of miR-218 in endothelial cells and determined it was responsible for the effect of miR-218 on tumor angiogenesis. In vivo, local injection of mature miR-218 in xenografted tumors disrupted the vessel plexus and thus inhibited tumor growth. Taken together, our study demonstrated an anti-angiogenic role of miR-218 in gastric cancer and indicated that delivery of miR-218 may be a potential therapeutic strategy to inhibit tumor angiogenesis.

BackgroundInfants breastfed on demand exhibit a variety of feeding patterns and self-regulate their nutrient intake, but factors influencing their gastric emptying (GE) are poorly understood. Despite research into appetite regulation properties of leptin, there is limited information about relationships between human milk leptin and infant GE.MethodsGastric volumes were calculated from ultrasound scans of infants' stomachs (n=20) taken before and after breastfeeding, and then every 12.5 min (median; range: 3-45 min) until the next feed. Skim milk leptin and macronutrient concentrations were measured and doses were calculated.ResultsThe leptin concentration was (mean±SD) 0.51±0.16 ng/ml; the leptin dose was 45.5±20.5 ng per feed. No relationships between both concentration and dose of leptin and time between the feeds (P=0.57; P=1, respectively) or residual stomach volumes before the subsequent feed (P=0.20; P=0.050) were found. Post-feed stomach volumes (GE rate) were not associated with leptin concentration (P=0.77) or dose (P=0.85).ConclusionGE in term breastfed infants was not associated with either skim milk leptin concentration or dose. Further investigation with inclusion of whole-milk leptin and other hormones that affect gastrointestinal activity is warranted.

This study aimed to investigate relationships between infant abdominal visceral and subcutaneous adiposity and human milk (HM) components and maternal body composition (BC) during first year of lactation. Subcutaneous-abdominal depth (SAD), subcutaneous-abdominal fat area (SFA), visceral depth (VD) and preperitoneal fat area of 20 breastfed infants were assessed at 2, 5, 9 and 12 months using ultrasound. Maternal BC was determined with bioimpedance spectroscopy. HM macronutrients and bioactive components concentrations and infant 24-h milk intake were measured and calculated daily intakes (CDI) determined. Maternal adiposity associated with infant SFA (negatively at 2, 5, 12, positively at 9 months, all overall p &lt, 0.05). 24-h milk intake positively associated with infant SAD (p = 0.007) and VD (p = 0.013). CDI of total protein (p = 0.013), total carbohydrates (p = 0.004) and lactose (p = 0.013) positively associated with SFA. Lactoferrin concentration associated with infant VD (negatively at 2, 12, positively at 5, 9 months, overall p = 0.003). CDI of HM components and maternal adiposity have differential effects on development of infant visceral and subcutaneous abdominal adiposity. Maintaining healthy maternal BC and continuing breastfeeding to 12 months and beyond may facilitate favourable BC development reducing risk of obesity.

Gastric carcinogenesis occurs when gastric epithelial cells transition through the initial, immortal, premalignant, and malignant stages of transformation. Epigenetic regulations contribute to this multistep process. Due to the critical role of epigenetic modifications , these changes are highly likely to be of clinical use in the future as new biomarkers and therapeutic targets for the early detection and treatment of cancers. Here, we summarize the recent findings on how epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, regulate gastric carcinogenesis, and we discuss potential new strategies for the diagnosis and treatments of gastric cancer. The strategies may be helpful in the further understanding of epigenetic regulation in human diseases.

Background: Diagnosis of the histological stage in primary biliary cholangitis (PBC) is essential for prognosis and further therapy. Noninvasive markers of liver fibrosis in PBC remain compelling. This study aimed to validate the diagnostic value of AST to ALT ratio (AAR), AST-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) in predicting histological severity among PBC patients combined with anti-gp210. Methods: A total of 208 PBC patients receiving liver biopsy with complete serological tests were enrolled. Clinical data including AAR, APRI and FIB-4 were compared with histological stage. Receiver operating characteristic analyses (ROCs) were used to assess the sensitivity and specificity of these markers with or without anti-gp210 in estimating liver fibrosis. Findings: The scores of AAR, APRI, and FIB-4 increased significantly according to the Ludwig's stage. Anti-gp210 was independently associated with liver fibrosis. The areas under the ROCs (AUCs) of AAR, APRI and FIB-4 combined with anti-gp210 for predicting advanced stage were 0.798, 0.816 and 0.834, respectively, which were superior to the AUCs of these markers predicting alone. The AUCs of AAR, APRI and FIB-4 for predicting advanced stage in the anti-gp210 positive patients were 0.748, 0.812 and 0.874, respectively. Using the best cutoff values of AAR, APRI, and FIB-4, 36.5%, 34.3% and 51.3% of patients could avoid liver biopsy, respectively. Interpretation: Indirect serum markers AAR, APRI, and FIB-4 represented a simple and reliable noninvasive surrogate marker of liver fibrosis especially in anti-gp210 positive PBC patients. Funding Statement: National Key Technology R&D Programme (2015BAI13B07). Declaration of Interests: All the authors declare no competing interests. Ethics Approval Statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Fourth Military Medical University. Informed consent was obtained in writing from each patient, and the study protocol was approved by the ethical committee of the Fourth Military Medical University

Human milk (HM) influences infant feeding patterns and body composition (BC). This small proof-of concept longitudinal study investigated relationships between infant/maternal BC and HM casein, whey and total protein during the first 12 months of lactation. BC of breastfeeding dyads (n = 20) was measured at 2 (n = 15), 5 (n = 20), 9 (n = 19), and/or 12 (n = 18) months postpartum with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). Proteins concentrations and 24-h milk intake were measured and calculated daily intakes (CDI) determined. Higher maternal weight, body mass index, fat-free mass, fat-free mass index, and fat mass index were associated with higher concentration of whey protein (p ≤ 0.034, n = 20). There were no associations between infant BC and concentrations of all proteins, and CDI of whey and total protein. Higher CDI of casein were associated with lower infant fat-free mass (p = 0.003, n = 18) and higher fat mass (p &lt, 0.001), fat mass index (p = 0.001, n = 18), and % fat mass (p &lt, 0.001, n = 18) measured with ultrasound skinfolds. These results show a differential effect of HM casein on development of infant BC during the first year of life, suggesting that there is a potential to improve outcome for the infant through interventions, such as continuation of breastfeeding during the first 12 months of life and beyond, which may facilitate favourable developmental programming that could reduce risk of non-communicable diseases later in life.

Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43–0.67, P

Background and aims Aberrant upregulation of POU2F2 expression has been discovered in metastatic gastric cancer (GC). However, the mechanisms underlying the aberrant upregulation and the potential functions of POU2F2 remain uncertain. Design The role and mechanism of POU2F2 in GC metastasis were investigated in gastric epithelial cells, GC cell lines and an experimental metastasis animal model by gain of function and loss of function. Upstream and downstream targets of POU2F2 were selected by bioinformatics and identified by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation PCR. The influence of miR-218 on its putative target genes (POU2F2, ROBO1 and IKK-β) and GC metastasis was further explored via in vitro and in vivo approaches. Results Increased POU2F2 expression was detected in metastatic GC cell lines and patient samples. POU2F2 was induced by the activation of nuclear factor (NF)-κB and, in turn, regulated ROBO1 transcription, thus functionally contributing to GC metastasis. Finally, miR-218 was found to suppress GC metastasis by simultaneously mediating multiple molecules in the POU2F2-oriented network. Conclusions This study demonstrated that NF-κB and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment.

Background Whether pre-existing nonvariceal spontaneous portosystemic shunts (SPSSs) in cirrhotic patients affect outcomes after transjugular intrahepatic portosystemic shunt (TIPS) and whether they need to be closed remains unclear. Aim To assess the effects of the presence or embolization of SPSSs on outcomes after TIPS for cirrhosis. Methods From January 2004 to December 2014, 903 consecutive cirrhotic patients who underwent TIPS in a tertiary-care center were included, of which 715 patients had no SPSS (N-SPSS group), 144 patients had an SPSS without embolization (SPSS group), and 44 had an SPSS with embolization (SPSS + E group). Results During a median follow-up period of 27.7 months, 368 (41%) patients experienced overt hepatic encephalopathy (OHE), 256 (28%) experienced clinical relapse, 164 (18%) developed shunt dysfunction, and 379 (42%) died. The SPSS group had a higher risk of OHE compared with the N-SPSS and SPSS + E groups (adjusted HR [95%CI]: N-SPSS vs SPSS vs SPSS + E: 1 vs 1.36 [1.06–1.75] vs 0.77 [0.46–1.29]; p = 0.027). In stratification analysis, a higher risk of OHE was only observed in patients with a large SPSS (SPSS diameter ≥6 mm) but not a small SPSS. Additionally, SPSS embolization was associated with a lower risk of OHE among patients with a large SPSS (adjust HR = 0.51; 95% CI: 0.29–0.91; p = 0.034). The risks of clinical relapse (p = 0.584), shunt dysfunction (p = 0.267), and mortality (p = 0.4743) did not significantly differ among groups. Conclusions Among cirrhotic patients undergoing TIPS, a pre-existing large SPSS was associated with a higher risk of OHE, which could be decreased by SPSS embolization. There was no clear association between the presence/embolization of an SPSS and post-TIPS clinical relapse, shunt dysfunction or mortality.

Inconsistent results of SOX2 expression have been reported in gastric cancer (GC). Here, we demonstrated that SOX2 was progressively downregulated during GC development via immunochemistry in 755 human gastric specimens. Low SOX2 levels were associated with pathological stage and clinical outcome. Multivariate analysis indicated that SOX2 protein expression served as an independent prognostic marker for GC. Gain-and loss-of function studies showed the anti-proliferative, anti-metastatic, and pro-apoptotic effects of SOX2 in GC. PTEN was selected as SOX2 targets by cDNA microarray and ChIP-DSL, further identified by luciferase assays, EMSA and ChIP-PCR. PTEN upregulation in response to SOX2-enforced expression suppressed GC malignancy via regulating Akt dephosphorylation. PTEN inhibition reversed SOX2-induced anticancer effects. Moreover, concordant positivity of SOX2 and PTEN proteins in nontumorous tissues but lost in matched GC specimens predicted a worse patient prognosis. Thus, SOX2 proved to be a new marker for evaluating GC outcome.

Purpose To assess the effects of preexisting nonmalignant portal vein thrombosis (PVT) on mortality, clinical relapse, shunt dysfunction, and overt hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) placement. Materials and Methods This retrospective study was approved by the institutional ethics committee, and written informed consent was obtained from all patients. From March 2001 to December 2014, 1171 consecutive patients with cirrhosis (762 men, 409 women; mean age, 50.0 years ± 12.8) and PVT (n = 212; 18%) or without PVT (n = 959; 82%) who underwent TIPS placement were included. The association between PVT and outcomes after TIPS placement was measured by using Fine and Gray competing risk regression model after adjusting for important baseline characteristics or by using propensity score. The Wald test was used to assess the homogeneity of the effects of PVT across different strata (stratified PVT according to the stages, degrees, and extents) and major subgroups. Results During a median follow-up period of 28.4 months, 507 (43%) patients died, 373 (32%) experienced clinical relapse, 217 (19%) developed shunt dysfunction, and 475 (41%) experienced overt HE. Compared with patients without PVT, patients with PVT had a similar risk of mortality (adjusted hazard ratio, 0.82; 95% confidence interval [CI]: 0.63, 1.09; P = .17), clinical relapse (adjusted hazard ratio, 1.24; 95% CI: 0.92, 1.69; P = .15), shunt dysfunction (adjusted hazard ratio, 1.03; 95% CI: 0.70, 1.51; P = .43), and overt HE (adjusted hazard ratio, 0.88; 95% CI: 0.70, 1.11; P = .29). Furthermore, the effects of PVT were consistent across the relevant strata and subgroups. Conclusion There was no evidence that preexisting PVT was associated with an improved or worsened outcome after TIPS.

SummaryBackground Use of TIPSS is associated with increases in ammonia concentration and hepatic encephalopathy (HE) risk. l-ornithine-l-aspartate (LOLA) is effective in reducing ammonia concentration. Aim To evaluate the effects of LOLA on venous ammonia concentration after TIPSS. Methods The included patients were randomised to receive LOLA or no-LOLA treatment for 7 days. Fasting and post-prandial venous ammonia levels were the primary outcomes. Psychometric performance, post-TIPSS HE, and liver and renal function were assessed as secondary outcomes. Results Of 133 cirrhotic patients who received successful TIPSS between November 2011 and June 2012, 40 met the inclusion criteria and were randomised to the LOLA (n = 21) or control (n = 19) groups. Change in fasting ammonia significantly favoured the LOLA group at days 4 (P = 0.001) and 7 (P = 0.003). Changes in post-prandial ammonia concentration significantly favoured the LOLA group at days 1, 4 and 7 as well. During the study period, patients in the LOLA group had better improvement in psychometric tests than those in the control group. Overt HE during treatment was observed in one patient in the LOLA group and three patients in the control group (P = 0.331). There were no differences in complications, adverse events or mortality between the two groups. Conclusions Prophylactic use of LOLA infusion after TIPSS is safe and effective in significantly reducing the increase of venous ammonia concentration, and can benefit the patient's mental status as well.

Human milk (HM) carbohydrates may affect infant appetite regulation, breastfeeding patterns, and body composition (BC). We investigated relationships between concentrations/calculated daily intakes (CDI) of HM carbohydrates in first year postpartum and maternal/term infant BC, as well as breastfeeding parameters. BC of dyads (n = 20) was determined at 2, 5, 9, and/or 12 months postpartum using ultrasound skinfolds (infants) and bioelectrical impedance spectroscopy (infants/mothers). Breastfeeding frequency, 24-h milk intake and total carbohydrates (TCH) and lactose were measured to calculate HM oligosaccharides (HMO) concentration and CDI of carbohydrates. Statistical analysis used linear regression/mixed effects models, results were adjusted for multiple comparisons. Higher TCH concentrations were associated with greater infant length, weight, fat-free mass (FFM), and FFM index (FFMI), and decreased fat mass (FM), FM index (FMI), %FM and FM/FFM ratio. Higher HMO concentrations were associated with greater infant FFM and FFMI, and decreased FMI, %FM, and FM/FFM ratio. Higher TCH CDI were associated with greater FM, FMI, %FM, and FM/FFM ratio, and decreased infant FFMI. Higher lactose CDI were associated with greater FM, FMI, %FM, and FM/FFM, ratio and decreased FFMI. Concentrations and intakes of HM carbohydrates differentially influence development of infant BC in the first 12 months postpartum, and may potentially influence risk of later obesity via modulation of BC.

Sleep plays a critical role in children's development. Sleep not only impacts on physical growth, behaviour, and emotional development but also is closely related to cognitive functioning, learning, and attention. Sleep problems that include nightmares, night terrors, sleep talking, sleepwalking, bed-wetting, teeth grinding and snoring are very common in Chinese children. In recent years, there has been improvement in the epidemiology of sleep problems in children of different ages in China. Despite growing research efforts, the aetiology of sleep problems has not been clearly identified. A number of surveys suggest that, in addition to biological determinants of sleep, sleep quality appears to be influenced in part by social, cultural and familial issues. In this review, we focus on assessing cultural aspects of sleep in Chinese children of different ages, especially young children. Particular emphasis is given to sociocultural factors (co-sleeping, transitional objects, child-rearing practices, feeding ...

We presented a rare case of chronic afferent loop obstruction after radical resection of gastric carcinoma. A 44- year-old man was admitted because of “upper abdominal distension and abdominal pain for 3 months, skin and sclera jaundice for 2 weeks”. Abdominal CT revealed dilatation of the intrahepatic bile duct and common bile duct, a large, abdominal cystic lesion, as well as left adrenal gland metastasis. MRCP revealed that the cystic lesion was an expansion of loops. Thus, the diagnosis of afferent loop (A-loop) obstruction was made. Subsequently, the patient underwent percutaneous transhepatic cholangial drainage (PTCD). The patient’s abdominal pain was significantly reduced, and the jaundice subsided. We should consider the possibility of the occurrence of the left adrenal metastasis and abdominal lymph node metastasis led to a chronic obstruction of A-loop. The chronic obstruction gradually developed into a complete blockage, further causing biliary obstruction and resulting in the occurrence of severe jaundice and abdominal pain. Here we not only reported a case of chronic afferent loop obstruction following radical resection of gastric carcinoma, but also analyzed the characteristic features of CT imaging and treatment. This case report is a good reference to similar gastrointestinal malignancy.

Human milk (HM) components influence infant feeding patterns and nutrient intake, yet it is unclear how they influence gastric emptying (GE), a key component of appetite regulation. This study analyzed GE of a single breastfeed, HM appetite hormones/macronutrients and demographics/anthropometrics/body composition of term fully breastfed infants (n = 41, 2 and/or 5 mo). Stomach volumes (SV) were calculated from pre-/post-feed ultrasound scans, then repeatedly until the next feed. Feed volume (FV) was measured by the test-weigh method. HM samples were analyzed for adiponectin, leptin, fat, lactose, total carbohydrate, lysozyme, and total/whey/casein protein. Linear regression/mixed effect models were used to determine associations between GE/feed variables and HM components/infant anthropometrics/adiposity. Higher FVs were associated with faster (−0.07 [−0.10, −0.03], p < 0.001) GE rate, higher post-feed SVs (0.82 [0.53, 1.12], p < 0.001), and longer GE times (0.24 [0.03, 0.46], p = 0.033). Higher whey protein concentration was associated with higher post-feed SVs (4.99 [0.84, 9.13], p = 0.023). Longer GE time was associated with higher adiponectin concentration (2.29 [0.92, 3.66], p = 0.002) and dose (0.02 [0.01, 0.03], p = 0.005), and lower casein:whey ratio (−65.89 [−107.13, −2.66], p = 0.003). FV and HM composition influence GE and breastfeeding patterns in term breastfed infants.

The effect of pethidine as patient-controlled epidural analgesia (PCEA) on specific biochemical components in breast milk in relation to the timing of secretory activation is not well investigated. The aim of this study was to compare biochemical timing of secretory activation between women who had a vaginal (V) or Caesarean birth with pethidine-PCEA (CBP). Several milk samples were collected daily from 36 mothers (17 V, 19 CBP) for the first 265 h post-partum. Protein and lactose concentrations and Na+ and K+ ion levels were measured. Samples were assigned to three time periods: 0-72, >72-165 and >165-265 h post-partum for statistical analyses. Data were analyzed using linear mixed effect models. In the first 72 h post-partum, the mean difference in lactose concentration was 5 gL-1 higher in group V (P 72-165 h post-partum, protein and Na+ concentrations were lower in group V (P = 0.05, P = 0.02), and K+ levels were higher in group V (P 165-265 h post-partum, there were no significant differences between the groups. Biochemically, secretory activation had occurred by 72 h post-partum in both groups. There were greater variations in measured biochemical components observed within group CBP initially. However, by 165 h post-partum, there were no differences in the biochemical components between the groups. This suggests that effects of pethidine-PCEA are diminished by 72 h post-partum and undetected by 165 h.

BackgroundThe human protection of telomeres 1 (hPOT1) protein, a single-strand telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. However, its effect on invasion of gastric cancer remains unclear.AimsTo explore the role of hPOT1 in the proliferation and invasion of gastric cancer cells.MethodsThe gastric expression of hPOT1 was examined in normal gastric mucosa (n=25), intestinal metaplasia (n=20), gastric dysplasia (n=20) and gastric cancer (n=150) by immunohistochemistry. The mean optical density (MOD) of the immunostaining was determined by semi-quantitative image analysis. The role of hPOT1 in the cell proliferation, apoptosis and invasion of gastric cancer 7901 cells was determined by means of the RNA interference (RNAi) of hPOT1 mRNA. The effects of hPOT1 RNAi on the expression of hPinX1 and hTERT were detected with western blotting.ResultsThe hPOT1 MOD was progressively increased from the normal mucosa to intestinal metaplasia, dysplasia, and gastric cancer. An increased hPOT1 expression significantly correlated with tumour serosal invasion, node metastasis and advanced stage. Transfection of hPOT1 siRNA into SGC-7901 cells led to a decrease in cell proliferation, colony formation and invasion, and also an increase of apoptosis. An up-regulation of hPinX1 and down-regulation of hTERT were found in gastric cancer cells with hPOT1 siRNA.ConclusionsIncreased hPOT1 expression is associated with an advanced tumour stage. hPOT1 RNAi inhibits proliferation and invasion, and induces apoptosis of gastric cancer cells. The effects of hPOT1 RNAi seem to be functionally linked to up-regulation of PinX1 and down-regulation of hTERT.

Epirubicin has been widely used for chemotherapeutic treatment of gastric cancer; however, intrinsic and acquired chemoresistance remains an obstacle to successful management. The mechanisms underlying epirubicin resistance are still not well defined. Here we report the construction and application of a partially randomized retrovirus library of 4 x 10(6) small interfering RNAs to identify novel genes whose suppression confers epirubicin resistance in gastric cancer cells SGC7901. From 12 resistant cell colonies, two small interfering RNAs targeting GAS1 (growth arrest-specific 1) and PTEN (phosphatase and tensin homolog), respectively, were identified and validated. We identified a previously unrecognized chemoresistance role for GAS1. GAS1 suppression resulted in significant epirubicin resistance and cross-resistance to 5-fluorouracil and cisplatin in various gastric cancer cell lines. GAS1 suppression promoted multidrug resistance through apoptosis inhibition, partially by up-regulating the Bcl-2/Bax ratio that was abolished by Bcl-2 inhibition. GAS1 suppression induced chemoresistance partially by increasing drug efflux in an ATP-binding cassette transporter and drug-dependent manner. P-glycoprotein (P-gp) and BCRP (breast cancer resistance protein) but not MRP-1 were up-regulated, and targeted knockdown of P-gp and BCRP could partially reverse GAS1 suppression-induced epirubicin resistance. Verapamil, a P-gp inhibitor, could reverse P-gp substrate (epirubicin) but not non-P-gp substrate (5-fluorouracil and cisplatin) resistance in GAS1-suppressed gastric cancer cells. BCRP down-regulation could partially reverse 5-fluorouracil but not cisplatin resistance induced by GAS1 suppression, suggesting 5-fluorouracil but not cisplatin was a BCRP substrate. These results suggest that GAS1 might be a target to overcome multidrug resistance and provide a novel approach to identifying candidate genes that suppress chemoresistance of gastric cancers.

Early response to therapy is one of the most important prognostic factors in childhood ALL. In the early 1980s, assessment of early treatment response to therapy relied mainly on morphological examination of peripheral blood or bone marrow after single-agent or multi-agent remission induction therapy. More recently, measurement of minimal residual disease (MRD) by flow cytometric detection of aberrant immunophenotype or by polymerase chain reaction of clonal T-cell receptor or immunoglobulin gene rearrangement emerged as a more reliable prognostic indicator. We evaluated the prognostic significance of early treatment response in our recent clinical trial. Among the children with ALL who entered protocol of ALL-XH-99 from January 1998 to May 2003, 193 patients with newly diagnosed ALL comprise the basis for this report. We examined blast cell count in the bone marrow on day 19 of remission induction and at the end of 35 days of remission induction. Minimal residual disease was measured with the use of flow cytometry. Probability of event-free survival was estimated by Kaplan-Meier analysis and the distributions of pEFS were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Univariate analysis indicated the probability of 4-year event-free survival (pEFS) was significantly worse for patients with ≥ 5% lymphoblasts in the bone marrow on day 19 as compared to those with less than 5% lymphoblasts on that date (42.59%±14.28% vs 74.24%±6.67%, P=0.0006). The probability of 4-year event-free survival (pEFS) was significantly worse for patients with any amount of lymphoblasts in the bone marrow on the remission date as compared to that of other patients with no morphologically identifiable blasts (63.47%±9.23% vs 76.41%±6.09%, P=0.0130). Patients who achieved a minimal residual level < 0.01%, fared significantly better than those with a higher level. (23.81%±20.26% vs 94.44%±5.4%, P=0.001). Early treatment response as assessed by morphologic examination or minimal residual leukemia determination by flow cytometry has important prognostic significance, and can be performed in a resource-poor patient population.

PURPOSE The aim of this study was to quantify the relationship between categories of body mass index (BMI) and age-related macular degeneration (AMD) risk in different stages. METHODS MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between BMI and incident early or late AMD. The analyses were based on data extracted from study reports. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of this association, and dose-response relationship was assessed by restricted cubic spline. RESULTS Seven prospective cohort studies with 1613 cases identified among 31,151 subjects were included. For overweight, the relationship remained insignificant for its association with both early AMD (RR = 0.92, 95% CI: 0.68-1.15; P = 0.54) and late AMD (RR = 1.09, 95% CI: 0.93-1.25; P = 0.18). A marked 32% increase in the risk of developing late AMD was noted among obese individuals (RR = 1.32, 95% CI: 1.11-1.53, P < 0.01), while obesity showed no significant association with early AMD (RR = 0.91, 95% CI: 0.74-1.08; P = 0.67). Furthermore, elevated BMI showed a linear dose-response relation with AMD risk (Pnonlinearity = 0.17), and the AMD risk increased by 2% (RR = 1.02, 95% CI: 1.01-1.04) for each 1 kg/m2 increase in BMI within the overweight and obese BMI ranges. CONCLUSIONS Excess body weight was weakly associated with increase in the risk of AMD in a dose-dependent fashion, especially for its late stage, indicating that keeping normal body weight and avoiding further weight gain may confer potential protection against this disease.

MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis., Author Summary MicroRNAs have been identified as playing important roles in tumor metastasis, but their impact on GC metastasis has been poorly explored. We have discovered miR-218, which functions as a suppressor of tumor metastasis and is correlated with clinical stage, lymph node metastasis, and prognosis in patients with GC. Our results show that miR-218 is part of a regulatory circuit involving the Slit-Robo1 pathway. In metastatic tumor cells, miR-218 was suppressed along with Slit3, one of its host genes. Meanwhile, Robo1, one of several Slit receptors, is upregulated in response to the decrease in miR-218, which in turn induced a reactive upregulation of the Slit-Robo1 pathway through an interaction with Slit2, thus facilitating tumor cell migration and invasion. Such findings not only provide new insights into the metastatic mechanisms in GC but also provide evidence for a novel miRNA–mediated regulatory mode of receptor signaling.

Objective In order to allow monitoring virtually all patients with childhood acute lymphoblastic leukemia for minimal residual disease in resource-poor countries or patient population. Methods Choice targets of minimal residual disease using tandem application of multi-parameter flow cytometry with various combinations of monoclonal antibodies for leukemia-associated immunophenotypes and polymerase chain reaction (PCR) of clonal T-cell receptor or immunoglobulin gene rearrangements was performed in 122 patients with newly diagnosis acute lymphoblastic leukemia on protocol ALL-XH-99. Results [circ1]The four-color antibody combinations consisted of CD10/CD34/CD19 plus another effective marker such as CD38, CD65, CD66c, and CD21. 106 cases of childhood B-cell precursor acute lymphoblastic leukemia were screening for antibodies combinations of interest and were identified in 95 of 106 cases (89.62%). The frequency of terminal deoxynucleotidyl transferase (TdT) in the immunophenotypic expression of leukemia cells is 59.43%, and then does CD38 and CD58. There is only one aberrant immunophenotype in 11 of 95 cases (11.58%) and most cases (88.42%) express at least two suitable combinations. [circ2] Due to lack of specimens in the leukemia cell bank, polymerase chain reaction of clonal T-cell receptor or immunoglobulin gene rearrangements was performed in 27 patients with newly diagnosis acute lymphoblastic leukemia including 7 cases with B-cell precursor ALL who were not detected targets of minimal residual disease by multi-parameter flow cytometry and 20 cases with T-lineage acute lymphoblastic leukemia (25 patients with T-ALL at the same time in our hospital). In 17 samples (65.38%), two or more monoclonal/bi-allelic gene rearrangements were identified, in 9 of 27 cases (34.62%), only one monoclonal rearrangement was detectable, and in one case no clonal T-cell receptor or immunoglobulin gene rearrangement could be identified. The vast majority (70%) of T-lineage ALL contain T-cell receptor VγI-Jγ1.3/2.3, and then T-cell receptor Vδ1-Jδ1, T-cell receptor VγIII-Jγ1.3/2.3. In B-cell precursor ALL, the high frequency of T-cell receptor VγI-Jγ1.3/2.3 emerged, and then the Kde rearrangements of IGK. Cross-lineage T-cell receptor rearrangements are found in many patients (57.14%) with B-lineage acute lymphoblastic leukemia. [circ3]Tandem application of multi-parameter flow cytometry with various combinations of monoclonal antibodies for leukemia-associated immunophenotypes and polymerase chain reaction (PCR) of clonal T-cell receptor or immunoglobulin gene rearrangements to detect MRD targets was investigated in 122 patients. Almost all patients except one case were detected suitable immunophenotypic abnormalities or antigen receptor gene rearrangements targets. Tandem application of two methods allows monitoring virtually all patients (99.18%) for MRD. Conclusion Choice targets of minimal residual disease using tandem application of flow cytometric detection of aberrant immunophenotypes, polymerase chain reaction (PCR) of clonal T-cell receptor or immunoglobulin gene rearrangements was to allow monitoring virtually in resource-poor countries or patient population for minimal residual disease.

PAX5 gene is a paired-box PAX gene family member,and encodes the transcription factor BSAP(B-cell specific activator protein) which is a key regulator of B-cell development and differentiation.Dysregulation of PAX5 gene function may contribute to tumorigenesis in lymphoid malignancies.But up to now,a detailed examination of PAX5/BSAP expression in acute leukemia(mainly acute B-lineage lymphoblastic leukemia) has not been reported.In this study,a real-time RT-PCR assay for the relative quantitation of PAX5 and CD19 mRNA expression was developed.It was applied on 6 haematological tumor cell lines and bone marrow cells of 6 normal children,58 previously untreated and 4 relapse acute leukemic children,including 39 cases of B-ALL,10 cases of T-ALL,and 13 cases of AML.PAX5 and CD19 mRNA expression were detected in B-cell lines tested,but almost not in other T- and myeloid cell lines.Among clinical samples,expression of PAX5 mRNA in B-ALL was significantly higher than that in T-ALL and AML(P=0.029 and P=0.013,respectively).PAX5 expression was significantly lower in T-ALL and AML than normal controls.The mRNA levels of PAX5 between T-ALL and AML had not any difference.Individual difference of PAX5 mRNA expression levels in children with B-ALL was great.Because binding sites for BSAP have been identified in the promoters of CD19,the study found that in B-ALL,there was clear correlation between the level of PAX5 expression and that of CD19,which was also studied by real-time RT-PCR.BSAP expression by Western Blotting analysis was also performed in haematological tumor cells,including 6 haematological tumor cell lines and 4 clinical samples(2 cases of B-ALL,1 case of T-ALL,and 1 case of AML).The results of Western Blotting analysis showed a 52-KD BSAP band in B lineage cells,but not in T- and myeloid lineage cells.The intensity of BSAP bands was in accordance with PAX5 mRNA expression level detected by real-time RT-PCR.It was concluded that PAX5 transcripts are readily detectable and quantified in clinical materials with B-ALL by real-time RT-PCR.The strong PAX5 mRNA expression in some B-ALL can be considered to be particularly interesting for further analysis.