There were significant increase in urine protein excretion,raised malondialdehyde(MDA) level and expressions of NF-?B,p22phox and p47phox in renal tissue,and significant decrease in reduced glutathione,superoxide dismutase,vitamin C and E levels in type 2 diabetic Goto-Kakisaki rats after 12 weeks. There was obvious histomorphologic change in the kidneys.All the above indices were improved by intraperitoneal injection of?-lipoic acid(35 mg/kg q.o.d).Besides,significant positive correlations were found of MDA level to p22phox,p47phox and NF-?B in the renal tissue,?-lipoic acid seems to protect the diabetic kidney in this diabetic rat model via antioxidative effects.

Adult ; Air Pollutants, Occupational ; adverse effects ; Chemical Industry ; Female ; Humans ; Insecticides ; adverse effects ; Male ; Maximum Allowable Concentration ; Middle Aged ; Occupational Diseases ; chemically induced ; diagnosis ; Organothiophosphorus Compounds ; adverse effects ; Phosphorus Compounds ; adverse effects ; Sulfides ; adverse effects

Adolescent ; Adult ; Anticoagulants ; therapeutic use ; Blood Coagulation Disorders ; diagnosis ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Vascular Malformations ; diagnosis ; drug therapy ; Veins ; pathology ; Young Adult

The dynamic expression of cytokines and phenotypes during the differentiation process of dendritic cell precursors (pre-DCs) to mature dendritic cells (DCs) was investigated,and the effects of inflammatory stimulation with lipopolysaccharide (LPS) on DCs differentiation were understood.The differentiation of bone marrow cells isolated from Balb/c mice was induced to DCs in an 8-day cell culture system with RPMI-1640 complete culture medium containing 10％ FBS,20 ng/mL recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and 10 ng/mL recombinant mouse interleukin-4 (rmIL-4).On the day 3,6 and 7 after culture,DCs were divided into non-LPS group and LPS group,given 500 ng/mL LPS for 24 h stimulation and no stimulation respectively.The expression levels of CD 1 l c+,MHC-Ⅱ +,CD40+,CD80+ and CD86+ were detected by flow cytometry,and those of IL-2,IL-4,IL-10,IL-12 p70 and IFN-γ in the supernatant by ELISA.On the day 3 and 6 after culture,the expression of IL-2,IL-4,IL-10 and IFN-γ in DCs showed no significant differences between non-LPS group and LPS group,whereas the differences were significant at day 7.The expression levels of cytokines (for IL-2,IL-4,IL-10,IFN-γ and IL-12 p70:152.86±6.91,778.33±8.35,44.55±2.54,5.8.26±1.09 and 2423.00±57.21 pg/mL respectively) in LPS group were higher than those in non-LPS group,especially IL-12 p70 increased obviously at day 7.It was concluded that during the differentiation process of pre-DCs to mature DCs,LPS stimulates DCs producing large amounts of IL-12 p70 and Thl-type cytokines as compared with Th2-type cytokines,and day 7 may be a key time-point for DCs polarization.

The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Alleles ; Amelogenin/genetics* ; Chromosomes, Human, Y ; Humans ; Male ; Sex Determination Analysis

Objective To investigate a more perfect method for a nice outward appearance of the thumb(finger) reconstructed.Methods An artery pedicle composite flap from fibular side of the great toe is inlaid in the tibial(ventral) side of the free second toe for thumb reconstruction and the same free second toe with a distal part of metatarsal bone with a double-wings flap for finger reconstruction before transplantation. Results The reconstructed thumb(finger) gets a nice looking and normal function while no blight to the great toe occurred.Conclusion It is an effective new procedure in ameliorating outward appearance of the recon- structed thumb(finger) by transferring the free moulded second toe.

An automatic inspection system for biochip's print quality is presented in this paper. It consists of an automatic mechanical control, a CCD sensor for getting the image of PET boart, and the special computer software for image processing and recognition. Experimental results indicate that this system is capable of providing a precise and effective realtime inspection for biochips' print quality.
Biosensing Techniques ; instrumentation ; methods ; Equipment Design ; Image Processing, Computer-Assisted ; methods ; Microchip Analytical Procedures ; methods ; Pattern Recognition, Automated ; methods ; Quality Control ; Software

Objetives To investigate the outcomes of sirolumus-eluting stent(CypherTM,Cordis/Johnson&Johnson,Warren,NJ,USA)and paclitaxel-eluting stent(TaxusTM,Boston Scientific,Natick,MA.USA)in the treatment of coronary heart disease after a four.year clinical follow-up.Methods 237 consecutive patients were enrolled in this study and treated with Cypher(136 patients)or Taxus(101 patients)from January to October 2003.111e rates of stenosis.stent thrombosis according to ARC definition and major adverse cardiac events(MACE a composite of cardiac death,myocardial infarction and target vessel revascularization)were analysed.Results There was no significant difference on secondary restenosis.target lesion revascularization(TLR)and MACE between Cypher and Taxus groups at six.month angiographic follow-up,but late luminal loss was higher in Taxus group[(0.15±0.43)mm vs(0.42±0.34)mm,P=0.022].At four-year follow-up,TVR-free survival rate was 88.97% in Cypher group versus 82.28% in Taxus group(P=0.158).MACE.free survival rate was 83.8% in Cypher group and 79.2% in Taxus group(P=0.056).The incidence of stent tllrombosis was no difference between the two groups(1.47% vs 1.98%).There was also no difference among early(0 vs 0.99%),late(0.73%vs0.99%)and very late stent thrombosis(0.73%vs 0)between the 2 groups.Conlusions There were nodifference between Cypher and Taxus in the treatment of coronary artery disease:Both Cypher and Taxus have good clinical outcomes except that Taxus had highcr late loss.