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.

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

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

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

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.

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.

OBJECTIVETo discuss the treatment of the scrotal vein malformation in teenagers and clinical efficacy.

METHODS32 cases with the local and diffuse scrotal vein malformation were retrospectively analyzed. 31 cases underwent local injection with 40% urea before resection. The urea was injected locally into tumor through multi-points within 30 seconds, 2-6 ml every time, one time a day. The injection was performed for 5-12 days. The treatment was refused in one case. The therapeutic effect and cosmetic result were recorded.

RESULTSThe tumors were removed radically in 28 cases including one operation in 25 cases and secondary operation in 3 cases. The patients were followed up for 1-3 years with no recurrence. Cosmetic result with bilaterally symmetric scrotum was satisfactory. The tumors in 3 severe cases were partially resected with improvement.

CONCLUSIONSCombined treatment with urea injection and surgical procedure can effectively treat the scrotal vein malformation with satisfactory result.

Adolescent ; Humans ; Injections, Intralesional ; Male ; Retrospective Studies ; Scrotum ; blood supply ; Urea ; administration & dosage ; therapeutic use ; Vascular Malformations ; therapy ; Young Adult

Objective To explore the clinical features of sleep disorder in patients with stroke and its related factors. Methods Two hundred and four patients with stroke, admitted to our hospital from January 2005 to June 2010, were chosen; Pittsburgh Sleep Quality Index (PSQI) was employed to determine whether these patients had sleep disorder; the prevalences of sleep disorder in patients with different ages, genders and lesions of stroke were compared. Symptom Checklist-90 (SCL-90)questionnaire was used to compare the physical and mental conditions of patients with or without sleep disorder; Hamilton Depression Rating Scales (HAMD), Barthel index, and National Institutes of Health Stroke Scale (NIHSS) were employed to compare the differences of depression, viability and neurologic impairment in patients with or without sleep disorder. Results The prevalence of sleep disorder was 46.6% (95/204), and it was higher in female group (53.8% vs 38.8%; x2=3.851, P=0.033). Patients aged ≥70 years had the highest rate of sleep disorder (57.6%), followed by patients aged ＜50 years (41.5%),and then patients aged between 50 and 69 years showed the lowest rate (32.9%). The sites of stroke located in the subcortex, cortex, and cerebellum enjoyed their prevalences of 64.2%, 27.4% and 4.5%,respectively. The incidence of sleep disorder in patients with stroke located in the left hemisphere was obviously higher than that in the right hemisphere (x2=7.688, P=0.008). The results of 9 indexes of SCL-90, scores of HAMD and NIHSS in patients with sleep disorder were significantly higher than those in patients without sleep disorder, while the Barthel index was in the opposite position with obvious differences (P＜0.05). Conclusion High prevalence of sleep disorder in patients with stroke is noted,which is related to gender, age of the patients and the sites of stroke, and may lead to depression, anxiety,neurological functional deficit and decrease of life quality. And we should pay more attention to nursing care during all the treatment.