Purpose: To evaluate the effect and safety of combination chemotherapy with oxaliplatin( L-OHP) plus 5-fluorouracil(5-FU)/folinic acid( CF) in advanced colorectal cancer( ACRC). Methods: 31 patients with ACRC entered the study. L-OHP 130 mg/m2 , iv infusion for 4 hours on day 1; CF 200 mg/m2 , iv infusion for 2 hours followed by 5-FU 500mg/ m , iv infusion for 4 hours from day 1 to day 5, repeated every 3 weeks. Results: There were 10 partial responses, 7 stable disease, 9 progressive disease, the response rate being 38. 5% . The main adverse effect was neuro-sensory toxicity which was seen in 90. 3% of the patients. Vomitting and diarrhea was observed in 58. 1% and 45. 2% of the patients respectively. Bone marrow suppression was mild. Conclusions: L-OHP combination with 5-FU/CF yields an encouraging response with acceptable toxicity in our study. Furthermore clinical reseach is worthwhile.

A total of 160 type 2 diabetic patients were divided into microalbuminuria(42 cases)and normoalbuminuria(118 cases)groups.Multivariate analysis demonstrated that the presence of microalbuminuria was independently associated with brachial-ankle pulse wave velocity(baPWV)and intima-media thickness(both P

Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.

Objective To investigate the difference of cerebral inter-hemispheric functional connectivity between the patients with amyotrophic lateral sclerosis ( ALS) and healthy controls ( HC) by a newly developed voxel-mirrored homotopic connectivity ( VMHC) method based on resting-state functional MRI ( rs-fMRI) , as well as its correlation to the structural imaging indices and clinical neurological scales .Methods Twenty patients with ALS ( ALS group ) and 20 age-, and sex-matched healthy controls ( HC group) were examined by rs-fMRI and diffusion tensor imaging ( DTI ) on 3.0 T MR imaging system ( Siemens Trio Tim ).The rs-fMRI data preprocessing were performed using data processing assistant for rs-fMRI ( DPARSF) based on Matlab 2009a, and the rs-fMRI data analysis toolkit ( REST) with an automated VMHC approach was utilized to calculate and compare the VMHC correlation coefficients between the ALS group and the HC group[P<0.05, corrected with false discovery rate (FDR)].Region of interest (ROIs) were prescribed on the regions which showed abnormal VMHC coefficients in ALS group , then the mean time series of the ROIs were extracted to examine the difference of the seed ( ROIs)-based functional connectivity between the ALS and HC groups.At last, linear correlations were performed to assess the relationships among the VMHC coefficients and clinical measures including the revised amyotrophic lateral sclerosis functional rating scale ( ALSFRS-r) score, disease duration , the rate of disease progression and fractional anisotropy ( FA) values of the corpus callosum ( CC).Results Compared with HC group , the patients with ALS showed lower VMHC coefficients in the precentral gyrus ( M1 ) , postcentral gyrus ( PCG ) , inferior parietal lobule (IPL), cuneus/precuneus (Cu/Pcu), and anterior cingulate gyrus (ACC).Higher VMHC coefficients were found in the supplementary motor area , superior frontal gyrus , and middle occipital gyrus (P<0.05,FDR corrected).Significant functional connectivity alterations were detected in motor cortex and frontal/temporal/occipital lobe between the ALS and HC groups using seed ( ROIs )-based functional connectivity based on the regions which showed abnormal VMHC coefficients in ALS group ( P <0.05, AlphaSim corrected, clusters≥228 voxels).Significant positive correlation was detected between the VMHC coefficients (0.311 ±0.108) of M1 and FA values (0.394 ±0.016) of CC III region (r=0.530, P=0.016), between the VMHC coefficients (0.767 ±0.043) of ACC and FA values (0.360 ±0.105) of CC I region (r=0.513, P=0.021), respectively.Significant positive correlation was observed between VMHC coefficients (0.311 ±0.108) of M1 and the ALSFRS-r score (35.4 ±2.5) in ALS patients(r=0.447, P=0.048).There was not significant correlation observed between the VMHC coefficients and disease duration , or the ratio of disease prognosis (P>0.05).Conclusions Abnormal VMHC coefficients were detected in ALS patients.The decreased VMHC in ACC and M1 are associated with the reduced micro-structure integrity of CC, meanwhile, and they may be related to disease severity.

0.05).There were no signifi-cant relation between the expressions of Fas,FasL and bcl-2and IL-8.Conclusion The abnormal expressions of Fas,FasL,bcl-2may play an important role in the pathogenesis of LN.The expression of Fas and FasL may serve as active indexes for SLE and LN.The low level of IL-8may be related to the dysfunction of immunity and needs further research.

OBJECTIVETo study the expression of phosphatase and tensin homology deleted on chromosometen ten (PTEN) protein, a tumor suppressor gene in breast cancer and its correlation with p27(kip1) and cyclin D1 expression.

METHODSPTEN protein expression, p27(kip1) and cyclin D1 protein expression were detected by immunohistochemical method in paraffin sections from 61 women with primary breast cancer. PTEN protein expression was compared with clinico-pathologic parameters as related to p27(kip1) and cyclin D1.

RESULTSPTEN, being shown in the cytoplasm, was negative in 6.6% (4/61), reduced in 41.0% (25/61) and positive in 52.5% (32/61) samples. PTEN expression level was correlated with axillary lymph node status, loss of estrogen receptor stain, recurrence and metastasis. On univariate analysis, the disease-free survival rate of patients with higher PTEN expression (> 50% cells stained) was better than those with lower expression (P = 0.0101). However, there was no correlation between p27(kip1), cyclin D1 expression or PTEN expression.

CONCLUSIONPTEN, its lower expression being correlated with poor outcome of breast cancer patients, plays a prominent role in breast cancer. p27(kip1) or cyclin D1 may not be the primary downstream genes of PTEN in breast cancer.

Adult ; Aged ; Breast Neoplasms ; chemistry ; mortality ; pathology ; Cyclin D1 ; analysis ; physiology ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphatic Metastasis ; Middle Aged ; PTEN Phosphohydrolase ; analysis ; physiology ; Prognosis

BACKGROUND: Nasal mucosa fibroblasts are reported to involve in inflammation and wound repair of various nasal diseases by secreting a variety of cytokines and chemokines. Guinea pig is a most suitable experimental animal for the study of allergic diseases. OBJECTIVE: To investigate the effective methods of isolation, culture, purification and identification of guinea pig nasal mucosa fibroblasts. METHODS: Guinea pig nasal mucosa fibroblasts were isolated by collagenase digestion, and purified by differential velocity adherence. The morphology of fibroblasts was observed by inverted phase contrast microscope, fibroblasts were identified by vimentin immunocytochemical staining, and the cell growth was detected by MTT assay to draw the growth curve. RESULTS AND CONCLUSION: (1) Under inverted phase contrast microscope, there were cells with different shapes in the primary nasal mucosa fibroblasts, most of which showed spindle-like and applanate shape, and cells were scattered distribution in cluster. The purified fibroblasts were homogeneous, mainly were long spindle-shaped, and distributed in fish shoal-like and radial-like. (2) Immunocytochemical staining indicated that fibroblasts were positive for vimentin. (3) The cell growth curve appeared to be typical S-shaped. (4) To conclude, the isolated and cultured cells exhibit typical biological characteristics of fibroblasts.

Objective To investigate the significance of the serum levels of interleukin-10 (IL-10),IL-13,IL-15 of patients with chronic hepatic failure and the correlation between those inter- leukin levels and nosocomial infections.Methods The serum levels of IL-10,IL-13,IL-15 of 58 patients with chronic hepatic failure were measured by double antibody sandwich enzyme-linked immu- nosorbent assay at the time of admission and 2 weeks after admission.Results The serum levels of IL-15 and the propotion of IL-15/IL-10 and IL-15/IL-13 in patients with chronic hepatic failure group at the time of admission were significantly higher than those in healthy control group[(358.16?290.91) ng/L vs (38.55?21.49) ng/L,12.93?14.26 vs 1.10?0.55,98.55?97.5.5 vs 9.70?5.03,respectively,all P=0.000].Those in death group were significantly higher than those in improving group[(479.93v205.52) ng/L vs (244.51?236.29) ng/L,17.65?17.78 vs 8.53?7.98,130.69?115.50 vs 68.55?65.99,respectively,all P

Objective To investigate the effects of intravenous immunoglobulin(IVIG) on apoptosis and necrosis of myocytes in mice with viral myocarditis.Methods Three hundreds and twenty Balb/c mice were randomly divided into 8 groups.Different courses of IVIG were given in varying time after virus inoculation,Chinese medicine Huangqi given in control group.The virus titer in myocardium、percentage of apoptosis and necrosis of myocytes were detected, myocardial histopathologic scores were counted.Results In every IVIG treatment group,the above 3 items were all significantly lower than that in virus control group and Huangqi group,as IVIG early long course group had the best effect.Conclusion IVIG may reduce the percentage of apoptosis and necrosis of myocytes and virus titer in myocardium in mice with viral myocarditis,the effects are better than that of Huangqi.

Atrioventricular Block ; etiology ; Cardiac Catheterization ; adverse effects ; Heart Septal Defects, Ventricular ; therapy ; Hematologic Diseases ; etiology ; Hemolysis ; Humans