Metabolic abnormality is correlated with the incidence of colorectal cancer.Metabolic syndrome is consisting of abdominal obesity,dyslipidemia,high blood pressure,sugar metabolic abnormality,and all of these factors are associated with colorectal cancer.Abdominal obesity and sugar metabolic abnormality may be the primary factors causing rectal cancer.Visceral fat is physiologically more active than subcutaneous fat.Visceral fat can produce and secret hormones and cytokines,which are involved in inflammation and metabolism,therefore the amount of visceral fat may directly or indirectly related to the occurrence of colorectal cancer.Obesity acts as a risk factor for colorectal cancer by several mechanisms,including high blood insulin,insulin-like growth factor,and the change of the adipose cytokines concentrations.Metabolic biomarkers may not only provide clues of colorectal carcinogenesis from the point of view of etiology,but also can help to explore new obesity phenotypes that is relevant to incidence risk of colorectal cancer.

Objective To establish the platelet antigen panel for identifying the specificity of platelet antibodies which cause platelet transfusion refractoriness and neonatal alloimmune thrombocytopenia and provide evidence for clinical therapy and platelet genotyping research.Methods Based on the frequency distribution of human platelet alloantigen (HPA)-1 to HPA-16 gene in China, the frequencies of HPA-1 to HPA-6,HPA-15 alleles in blood group O donors were genotyped by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method, and suitable donors were chosen to establish platelet-specific antigen panel.Using the established platelet-specific antigen panel, the specificity of platelet antibodies caused by alloimmune reaction was identified by using simplified sensitized erythrocyte platelet serology assay (SEPSA).Results Eleven ptatelet donors with blood group O were chosen to establish platelet-specific antigen panel which can identify specificity of HPA-1 to HPA-6, HPA-15 antibodies.One case of HPA-4b (Penb) and two cases of HPA-15a (Govb) platelet specific antibodies were detected in 1 120 samples.Conclusion Identifying the specific platelet antibodies using platelet specific antigen panel has profound significance on increasing the safety and effectiveness of clinical platelet transfusion and prevention of neonatal alloimmune thrombocytopenia.

Objective To clarify the role and significance of Toll?like receptor 4(TLR4)in myocardial damage following paraquat(PQ)poisoning in mice. Methods Male wild type C57BL/6J mice(WT)and male TLR4 deficient mice(TLR4?ko)were divided into four groups in the study:(1)control group(WT mice,n=6);(2)TLR4?ko group(TLR4?ko mice,n=6);(3)WT+PQ group(WT mice,n=30);(4)TLR4?ko+PQ group (TLR4?ko mice,n=30). The mice in group 1 and group 2 were injected intraperitoneally with saline;mice in group 3 and group 4 were injected in?traperitoneally with 75 mg/kg of PQ. At 2 h,4 h,8 h,16 h and 24 h after PQ administration,6 mice of WT+PQ group and TLR4?ko+PQ group were euthanized and the heart tissue specimens were harvested. All the specimens were analysed by histology,while the expression of TLR4 mRNA was only detected in samples of WT+PQ mice. The specimens at 2 h,8 h and 24 h after PQ administration were used for cytokines detection for WT+PQ group and TLR4?ko+PQ group;in addition,Western blot analysis was performed for WT+PQ group. At 8 h after treatment,control mice and TLR4?ko mice were euthanized by the same method. Mice were anesthetized for cardiac geometry and functional assessment using a 2?D guide M?mode echocardiography at 8 h following injection of either PQ or saline. Results During myocardial damage due to PQ exposure in WT+PQ mice,obvious histopathological changes were observed,as well as a noticeable decrease of heart function and increased expressions of TNF?αand IL?1β. Compared with the WT mice,TNF?αand IL?1βprotein levels,changes in heart function and histopathological changes were significantly attenuated following PQ exposure in myocardial damage in TLR4?ko mice. Conclusion The TLR4gene is involved with in heart functional injury and histopathological changes in myocardial damage following PQ poisoning in mice,which may through the regulation of TNF?αand IL?1βexpression. Our findings indi?cate that TLR4 plays an important role in mediating myocardial injury due to PQ.

The surgical approach for rectal cancer includes trans-abdominal and transanal excision. Total mesorectal excision(TME) is the golden standard for surgical treatment. In the functional surgery era, more and more evidence shows that under strict indications, traditional abdominal radical surgery and transanal excision can achieve similar survival in patients with early stage cancer. However, the local recurrence rate of local resection was significantly higher compared to TME, suggesting strict patients selection for transanal excision. Preoperative accurate evaluation is critical in clinical practice.
Anal Canal ; surgery ; Digestive System Surgical Procedures ; methods ; Humans ; Rectal Neoplasms ; surgery

Objective To investigate the protective effect and underlying mechanism of the superoxide dismutase mimic, manganese (Ⅲ) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), on paraquat (PQ) -induced lung epithelial-like cell injury. Methods Alveolar epithelial-like cells (A549) were pretreated with 10 μmol/L of MnTMPyP for 1.5 h and then cultured with or without PQ (750 μmol/L) for 24 h. Cell survival was determined using the MTT assay. Reactive oxygen species (ROS) production and Ca2+ levels were measured using flow cytometry. Glutathione reductase (GR) activity was determined using spectrophotometry. Expressions of the endoplasmic reticulum (ER) stress proteins, glucose regulatory protein 78 (Grp78) and C/EBP homologous protein (CHOP), were measured using Western blotting. Results Cell viability and GR activity were decreased, but ROS production, cytoplasmic Ca2+ levels, and expressions of Grp78 and CHOP were all increased in the PQ group compared to those in the control group. There were no statistically significant changes in the MnTMPyP group. Cell viability and GR activity were increased, while ROS production, cytoplasmic Ca2+ levels, and expressions of Grp78 and CHOP were all significantly reduced in the MnTMPyP group compared to those in the PQ group. Conclusion MnTMPyP effectively reduced PQ-induced lung epithelial-like cell injury, and the underlying mechanism is related to antagonism of PQ-induced ER stress and oxidative stress.

Objective To investigate the apoptosis mechanism induced by paraquat (PQ) in human type Ⅱ alveolar epithelial-like A549 cells.Methods A549 cells were cultured in vitro.The cells in the experimental group were exposed to various concentrations of PQ (50,100,150,and 200 μmol/L),while those in the control group were cultured in RPMI1640 medium.After treatment for 24 and 48 h,the cell survival rate was assessed by MTT assay.Morphological changes in the nuclei were observed by Hoechst 33258 fluorescence staining.Cellular apoptosis and mitochondrial transmembrane potential were assayed by flow cytometry.The activities of caspase-3 and caspase-9 were assayed by spectrophotometry.Western blotting was used to analyze the expression of proteins in the Bcl-2 family,such as Bcl-2,Bcl-xL,Bax,and Bak.Results PQ exhibited significant anti-proliferative activity in A549 cells.PQ-treated A549 cells were subjected to Hoechst 33258 staining.The hallmarks of apoptosis were detected,and the degree of apoptosis increased.Mitochondrial membrane potential was decreased,the levels of active caspase-3 and caspase-9 increased,the expression of Bcl-2 and Bcl-xL was decreased,and the expression of Bax and Bak was increased.These effects occurred in concentration-and time-dependent manners.Conclusion PQ efficiently induced intracellular apoptosis through the mitochondrial pathway in A549 cells.

OBJECTIVETo investigate the prognostic factors of colorectal cancer patients with liver metastasis in order to provide reference for clinical practice.

METHODSClinicopathological and follow-up data of 264 cases of colorectal liver metastasis in our department from January 1997 to January 2012 were analyzed retrospectively. Among these 264 patients, 217 underwent primary colorectal cancer resection, 33 underwent combined resection of primary colorectal lesion plus liver metastasis, and 14 received stoma creation alone. Besides, 197 patients received adjuvant chemotherapy, 14 received adjuvant radiotherapy, and 42 underwent interventional treatment. Clinicopathological features and treatment scheme affecting prognosis were analyzed and prognostic stratification analysis was performed according to emergence time of liver metastasis (synchronous or metachronous).

RESULTSOf 264 patients, 1-, 3-, and 5-year overall survival rates were 77.0%, 31.7%, and 14.0%; median survival time was 25 months; 1-, 3-, and 5-year survival rates of synchronous colorectal liver metastasis were 68.8%, 22.3%, and 7.7%; 1-, 3-, and 5-year survival rates of metochronous colorectal liver metastasis were 95.8%, 49.0%, and 21.3%, whose difference was statistically significant (P<0.05). Multivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05).

CONCLUSIONSRadical operation and adjuvant chemotherapy should be emphasized for colorectal liver metastasis, especially for synchronous colorectal liver metastasis. Simple resection of primary tumor can not improve the overall survival of patients with colorectal liver metastasis.

Chemotherapy, Adjuvant ; Colorectal Neoplasms ; pathology ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; therapy ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Rate

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*