With the widely application of the metagenomics, the relationship between microbiota and disease has become a hot research topic. Understanding the potential association between upper gastrointestinal cancer or precancerous lesions and microbiota may play an important role in the early detection, clinical diagnosis and treatment, and prognostic evaluation of upper gastrointestinal cancer. Therefore, a literature retrieval was conducted by using PubMed, Embase and wanfang databases to summarize the latest research progress in the microbiota of upper gastrointestinal cancer, including oral, esophageal, gastric cancer and precancerous lesions. Lower microbial diversity or richness in esophageal cancer and precancerous lesions and specific prognostic biomarkers for esophageal cancer were found. Lactobacillus richness showed an increase trend during the process from gastritis to gastric cancer. This paper summarizes the progress in the research of potential biological etiology of upper gastrointestinal cancer from the perspective of metagenomics in order to provide evidence on the, prevention and control of upper gastrointestinal cancer.
Esophageal Neoplasms/microbiology* ; Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/microbiology* ; Gastrointestinal Tract/microbiology* ; Humans ; Lactobacillus ; Metagenomics/trends* ; Microbiota ; Precancerous Conditions/microbiology* ; Prognosis ; Research/trends* ; Risk Factors ; Stomach Neoplasms/microbiology*

OBJECTIVE TNF- related apoptosis- inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors. However, most breast cancer cells are resistant to TRAIL- induced apoptosis. Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance. METHODS To identify modulators of TRAIL-induced apoptosis, we carried out a genome wide siRNA screen. To validate the screening result, we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model. Finally, we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy. RESULTS We unexpectedly identified androgen receptor (AR) to be responsible for TRAIL resistance. While AR is classically viewed as the key factor in prostate cancer progression, we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple- negative breast cancers (TNBC) that are highly aggressive with poor prognosis. Importantly, breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance. AR overexpression in MDA- MB- 231 and MDA- MB- 436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis. AR overexpression also induced TRAIL resistance in breast tumors in vivo. Further, we observed an upregulation of the TRAIL receptor, death receptor 5 (DR5) in breast cancer cells, following the removal or inhibition of AR by its antagonists Casodex and MDV3100. Treatment with AR antagonists also enhanced TRAIL- induced breast cancer cell apoptosis. CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis, in part, by suppressing DR5 expression, and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.

INTRODUCTIONUltrasound-guided fine-needle aspiration cytology (US-FNAC) of thyroid nodules is an important diagnostic procedure. In most hospitals, patients are referred to radiologists for US-FNAC, but this often results in a long waiting time before results are available. Surgeon-performed US-FNAC (SP-US-FNAC) during the initial patient consultation attempts to reduce the waiting time but it is not known whether this is as accurate as radiologist-performed US-FNAC (RP-US-FNAC). The aim of this study is to compare the clinical efficiency between SP-US-FNAC and RP-US-FNAC.

MATERIALS AND METHODSA retrospective study was performed on patients from the Department of General Surgery, Tan Tock Seng Hospital (TTSH) who underwent an US-FNAC from August 2011 to May 2012. All cases of SP-US-FNAC were performed by a single surgeon. This study compared the rates of positive diagnoses achieved by SP-US-FNAC and RPUS- FNAC as well as the time interval to reach a cytological diagnosis by each group.

RESULTSA total of 40 cases of SP-US-FNAC and 72 cases of RP-US-FNAC were included in the study. SP-US-FNAC resulted in 28 (70%) positive diagnoses and 12 (30%) nondiagnoses while RP-US-FNAC resulted in 47 (65.3%) positive diagnoses and 25 (34.7%) non-diagnoses. These results were comparable (P=0.678). The median time taken to reach a cytological diagnosis was 1 working day for SP-US-FNAC and 29.5 working days for RP-US-FNAC resulting in a shorter interval to reaching a cytological diagnosis for SP-US-FNAC (P<0.001).

CONCLUSIONIn the workup of thyroid nodules, SP-US-FNAC is as accurate as RP-US-FNAC but significantly reduces the time taken to reach a cytological diagnosis. This leads to greater clinical efficiency in the management of patients with thyroid nodules, which in turn leads to other benefits such as decreased patient anxiety and increased patient satisfaction.

Adult ; Biopsy, Fine-Needle ; methods ; Female ; Humans ; Image-Guided Biopsy ; Male ; Middle Aged ; Retrospective Studies ; Specialties, Surgical ; Thyroid Nodule ; pathology ; Time Factors

Facial scar and deformation caused by burn injury severely affect physical and psychological well-being of pediatric burn patients, which needs medical workers and pediatric burn patients′ family members to pay much attention to and to perform early rehabilitation treatment. Pressure therapy is an important rehabilitative strategy for pediatric burn patients with facial scar, mainly including wearing headgears and transparent pressure facemasks, which have their own features. To achieve better treatment results, pressure therapy should be chosen according to specific condition of pediatric burn patients and combined with other assistant therapies. Successful rehabilitation for pediatric burn patients relies on cooperation of both family members of pediatric burn patients and society. Rehabilitation knowledge should be provided to parents of pediatric burn patients to acquire their full support and cooperation in order to achieve best therapeutic effects and ultimately to rebuild physical and psychological well-being of pediatric burn patients.

PURPOSE: Liver, unlike heart or skin, allografts transplanted between MHC-disparate mouse strains are spontaneously accepted without any immunosuppressive therapy. Despite the allograft acceptance, the recipients continue to exhibit donor-specific immune responses in vitro (MLR and generation of CTL). High levels of CTL apoptosis evident within tolerated liver grafts have been postulated as a mechanism underlying this 'split' tolerance. METHODS and RESULTS: By using radiometric DNA fragmentation test ("JAM" assay) and TUNEL staining, we present the evidence here that liver nonparenchymal cells (NPC) are quite strong inducers of activated T cell apoptotic death in allogeneic mice. This phenomenon occurs the similar level in activated T cells of syngeneic or third-party mice. Liver cells from gld (FasL-deficient) mice exert similar apoptosis-inducing effect on activated T cells from normal mice. Tumor necrosis factor receptor (TNFR): Fc fusion protein, and concanamycin A, an inhibitor of perforin pathway, fail to inhibit the apoptotic activity. CONCLUSION: These data indicate that liver NPC play important role in causing active apoptosis in graft-infiltratingCTL which favors liver graft acceptance, and liver-induced activated T cell apoptosis may not mediated by Fas, TNF or perforin pathways.
Allografts ; Animals ; Apoptosis* ; DNA Fragmentation ; Heart ; Immune Tolerance ; In Situ Nick-End Labeling ; Liver* ; Mice ; Perforin ; Receptors, Tumor Necrosis Factor ; Skin ; T-Lymphocytes* ; Transplantation ; Transplants

INTRODUCTIONBreast cancer is the most common malignancy in pregnant women, occurring at a rate of about 1 in 3000 pregnancies. Unfortunately, this will sometimes occur during the first trimester of pregnancy and this situation warrants discussion of management options with regard to the mother and child, especially with the current trend of deferring child bearing to a later age.

CLINICAL PICTUREWe present a 34-year-old primigravida who had a breast lump prior to confirmation of her pregnancy and received her diagnosis of invasive breast cancer at 7 weeks' amenorrhoea. The oncologic management options of this pregnant patient with breast cancer are discussed.

TREATMENTThe patient eventually opted to undergo wide excision of the breast cancer with sentinel lymph node biopsy and possible axillary clearance together with termination of her pregnancy.

RESULTSThe patient successfully underwent surgery for her breast cancer and was subsequently treated with adjuvant therapy as per normal protocol for a non-pregnant patient.

CONCLUSIONThe management of breast cancer and pregnancy occurring concurrently is a complex problem fraught with many dilemmas for both the medical team, the patient and her family. The option chosen must involve a multidisciplinary team and have full informed consent of the patient.

Abortion, Induced ; Adult ; Breast Neoplasms ; diagnosis ; drug therapy ; surgery ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, First ; Sentinel Lymph Node Biopsy

OBJECTIVETo investigate the molecular mechanism of human ether-a-go-go-related gene (HERG) potassium channels regulated by protein kinase A (PKA) in a human cell line.

METHODSHERG channels were stably expressed in human embryonic kidney (HEK) 293 cells, and currents were measured with the patch clamp technique. The direct phosphorylation of HERG channel proteins expressed heterologously in Xenopus laevis oocytes was examined by (32)P labeling and immunoprecipitation with an anti-HERG antibody.

RESULTSElevation of the intracellular cAMP-concentration by incubation with the adenylate cyclase activator, forskolin (10 micromol/L), and the broad range phosphodiesterase inhibitor, IBMX (100 micromol/L), caused a HERG tail current reduction of 83.2%. In addition, direct application of the membrane permeable cAMP analog, 8-Br-cAMP (500 micromol/L), reduced the tail current amplitude by 29.3%. Intracellular application of the catalytic subunit of protein kinase A (200 U/ml) led to a tail current decrease by 56.9% and shifted the activation curve by 15.4 mV towards more positive potentials. HERG WT proteins showed two phosphorylated bands, an upper band with a molecular mass of approximately 155 kDa and a lower band with a molecular mass of approximately 135 kDa, indicating that both the core- and the fully glycosylated forms of the protein were phosphorylated.

CONCLUSIONSPKA-mediated phosphorylation of HERG channels causes current reduction in a human cell line. The coupling between the repolarizing cardiac HERG potassium current and the protein kinase A system could contribute to arrhythmogenesis under pathophysiological conditions.

1-Methyl-3-isobutylxanthine ; pharmacology ; 8-Bromo Cyclic Adenosine Monophosphate ; pharmacology ; Adenylyl Cyclases ; metabolism ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Cation Transport Proteins ; Cell Line ; Colforsin ; pharmacology ; Cyclic AMP ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; DNA-Binding Proteins ; ERG1 Potassium Channel ; Enzyme Activation ; drug effects ; Ether-A-Go-Go Potassium Channels ; Female ; Humans ; Membrane Potentials ; drug effects ; Microinjections ; Oocytes ; Patch-Clamp Techniques ; Phenethylamines ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; Phosphoric Diester Hydrolases ; drug effects ; metabolism ; Phosphorylation ; Potassium Channels ; genetics ; metabolism ; physiology ; Potassium Channels, Voltage-Gated ; RNA, Complementary ; administration & dosage ; genetics ; Sulfonamides ; pharmacology ; Trans-Activators ; Transcriptional Regulator ERG ; Xenopus laevis

OBJECTIVETo investigate the feasibility of nitrogen and phosphorus recovery from swine waste biogas digester effluent and the effects of pH and NH4+: Mg2+: PO4(3-) molar ratio on its precipitation.

METHODSPrecipitation experiments with swine waste biogas digester effluent were conducted at pH 7.5, 8.0, 8.5, and 9.0 together with NH4+: Mg2+: PO4(3-) molar ratios 1: 0.2: 0.08, 1: 1: 1, and 1: 1.5: 1.5. Chemical and X-ray diffraction (XRD) analysis were done to determine the composition of the precipitate.

RESULTSThe highest removal and recovery of NH4+ and PO4(3-) were achieved at pH 9.0 in each experiment. The elevation of pH to 9.0 alone could decrease the initial PO4(3-) concentration from 42 mg L(-1) to 4.7 mg L(-1) and 89.2% PO4(3-) recovery was achieved. The pH-molar ratio combination 9.0-1: 1.5: 1.5 effected 76.5% NH4+ and 68.5% PO4(3-) recovery. The molar ratio of 1: 1: 1 together with pH elevation to 9.0 was determined to be the optimum combination for both NH4+ and PO4(3-) removal as it recovered over 70% and 97% of the initial NH4+ and PO4(3-), respectively.

CONCLUSIONSNitrogen and phosphorus can be recovered from biogas digester effluent as struvite.

Animals ; Bioelectric Energy Sources ; Bioreactors ; Chemical Precipitation ; Hydrogen-Ion Concentration ; Magnesium Compounds ; chemistry ; isolation & purification ; Manure ; Nitrogen ; chemistry ; isolation & purification ; Phosphates ; chemistry ; isolation & purification ; Phosphorus ; chemistry ; isolation & purification ; Struvite ; Swine ; Waste Disposal, Fluid ; X-Ray Diffraction

OBJECTIVETo investigate the struvite precipitation under constant and non-constant pH conditions and to test a stainless steel device under different operating regimes to maximize the recovery of struvite.

METHODSThe molar ratio of NH4+: Mg2+: PO4(3-) was adjusted to 1: 1.2: 1.2 and pH was elevated to 9.0. The absorbance measurement was used to trace the process of struvite crystallization. Wastewater and precipitate analysis was done by standard analytical methods.

RESULTSThe pH constant experiment reported a significantly higher struvite precipitation (24.6 +/- 0.86 g) than the non-constant pH experiment (19.8 +/- 1.86 g). The SAR ranged from 5.6 to 8.2 g m(-2) h(-1) to 3.6-4.8 g m(-2) h(-1) in pH constant and non-constant experiments, respectively. The highest struvite deposit on the device was found in regime 3 followed by in regimes 2 and 4. The highest PO4(3-) (97.2%) and NH4+ (71%) removal was reported in the R1 regime. None of the influent Cu2+ or Zn2+ was precipitated on the device.

CONCLUSIONA higher struvite yield is evident in pH constant experiments. Moreover, the stainless steel device facilitates the isolation of heavy metal free pure (around 96%) struvite from swine waste biogas digester effluent contaminated with cu2+ and Zn2+ and the highest yield is attainable with the device operating at 50 rpm with agitation by a magnetic stirrer.

Animals ; Bioreactors ; Chemical Precipitation ; Hydrogen-Ion Concentration ; Magnesium Compounds ; chemistry ; Manure ; Phosphates ; chemistry ; Stainless Steel ; Struvite ; Swine ; Time Factors ; Waste Disposal, Fluid ; instrumentation ; methods

OBJECTIVETo assess the relationship between microglia activation and apoptosis of neurons, and the significance of activated microglias in the formation and progression of senile plaques in Alzheimer's disease.

METHODSIL-1alpha and beta-amyloid immunohistochemistry, combined with TUNEL assay were used to assess brain tissue samples from 10 patients with Alzheimer's disease and 4 negative control cases without neurological disease.

RESULTSThe number of resting microglias in the brains of Alzheimer's disease patients was similar to that of the control group (P > 0.05), but the number of activated microglias was significant greater in the Alzheimer's disease patients than that of the controls (P < 0.01). The activated microglias displayed altered size and morphology, and was therefore, categorized into three subtypes as primed, enlarged and phagocytic microglias. The numbers of primed, enlarged and phagocytic microglias were 5.4 +/- 0.87, 11.5 +/- 1.25, and 3.4 +/- 0.32 microglia/mm2 and represented 26.6%, 56.65%, and 16.75% of all activated microglias respectively. The number of TUNEL positive apoptotic neurons was significantly greater in Alzheimer patients than that in the control group (P < 0.05). There was a close relationship between the apoptosis of neurons and the activation of microglias (P < 0.01). The activated microglias were differentially distributed among four different plaque types in Alzheimer patients. Many primed (42.3%) and most of the enlarged and phagocytic microglias (56.2% and 70.6%) were present in the diffuse neuritic plaques.

CONCLUSIONSHyperplasia and activation of microglias are a common phenomena in AD and may play an important role in its pathogenesis. There is a close relationship between the apoptosis of neurons and activation of microglias. The activation of microglias may play a key pathogenic role in senile plaque formation and progression of Alzheimer disease.

Aged ; Alzheimer Disease ; etiology ; pathology ; Amyloid beta-Peptides ; analysis ; Apoptosis ; Cell Count ; Cell Differentiation ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Interleukin-1 ; analysis ; Microglia ; chemistry ; classification ; pathology ; Middle Aged ; Phagocytes ; pathology