ObjectiveTo evaluate the clinical application of endovascular treatment for severe Takayasu's arteritis (TA).MethodsIn this study,35 target lesions in 32 patients [28 women,mean age (30 ±8) years] with severe Takayasu's arteritis were treated with endovascular merthod.The average length of lesion was 3.1 cm( range 2.7 -5.3).The overall average degree of diameter stenosis was 90％ ± 11％ (range 70- 100)in which 15 lesions were completely occlusive.There were 10 patients whose ESR were higher than 20 mm/h( range 25 -37).Follow-up included physical examination and patency evaluated by color duplex souography/computed tomography angiography/angiography at 6 months and then annually.ResultsRecanalization was unsuccessful in 3 completely occlusive lesions,with a successful rate of 80％(12/15).There was one case in which embolization leading to acute thrombogenesis developed during interventional procedure and resulting in severe stroke.The technical successful rate ( residual stenosis ＜ 50％ ) was 88.6％ ( 31/35 ).The transient cerebral ischemia attack ( TIA ) symptoms disappeared in 31 cases.26 cases were followed up for an average of (19 ± 10) months (range 13 -40).Occipital infarction following severe in-stent restenosis developed 13 months later in one case.Symptomatic in-stent restenosis18monthslaterwasfoundin2cases. Patencyratewas88.5％( 23/26 ).ConclusionsEndovascular treatment is safe and effective for severe TA.Strict indication and accurate targeting the lesions help ensure the success of management.

ObjectiveTo evaluate the clinical safety and efficacy of SilverHawk directional atherectomy for femoropopliteal occlusive lesions. MethodsEighteen ischemia occlusive lesions in 11 patients of the lower extremity were treated with SilverHawk directional atherectomy.The mean lesion number was 1.6 ± 1. 1 per patient. The mean lesion length was ( 3.4 ± 2. 2 ) cm. The average degree of diameter stenosis was 96％ ± 14％. 9 lesions were totally occlusive. Clinical symptoms included claudication in 4 cases ( Rutherford classes: 3) and critical limb ischemia ( Rutherford classes: 4) in 7 cases. Lesions characteristics were divided by TASC classification: TASC B in 7 cases; TASC C in 1 case (in-stent occlusion); TASC D in 3 cases.Mean ABI was 0. 5± 0.4. Patency was evaluated with color duplex sonography or CTA besides clinical examination during follow-up.ResultsNine totally occlusive lesions were recanalizated successfully via intraluminal approach. 18 lesions achieved technical success (residual stenosis ＜50％ ) leaving 15％ ±7％ mean residual stenosis in mean (8 ±3)min, predilation was needed in one lesion ( in-stent occlusion) prior to atherectomy. Clinical symptoms improved or disappeared with mean ABI 1.07 ±0. 12 and Rutherford grades: 0 (n =9) and 1 (n =2). Patency rate was 100％ with mean 0. 93 ± 0. 14 ABI and Rutherford grades remain unchanged after follow-up of mean ( 9 ± 4 ) monthes.ConclusionsSilverHawk directional atherectomy is safe and effective for the treatment of lower extremity ischemia.

A canine distemper virus strain was isolated from the lung of dog coming from Aksu in Xing Jiang using lung primary M cell during the CDV molecular epidemiological study. It was demonstrated to be a virulent strain of CDV by a series of systematic identification such as morphology , serology neutralization test, canine infection test, and molecular virology test.

OBJECTIVETo explore the relationship between the expression of heat shock protein 90, 60 and 27 (HSP90, HSP60 and HSP27) and genetic damage in peripheral blood of workers exposed to coke oven emissions.

METHODS288 coke oven workers in a steel factory were divided into the high-dose group and the low-dose group on the basis of environment monitoring result and work place. There were 172 men in high-dose group (workers who worked at the oven top and oven side) and 116 men in low-dose group (workers who worked at the oven bottom and others who were engaged to aided work). 38 workers unexposed occupationally to carcinogenic substances were selected as the control group, who were employed in medical therapy unit nearby 2 kilometers from the steel factory. Their general information, history of personal and occupational exposure, and the work environment were investigated. Blood samples were collected immediately after a shift at the end of a working day from 288 coke oven workers and 38 control workers. Levels of HSP90, HSP60 and HSP27 in peripheral blood lymphocytes were measured by Western blot, and the degree of DNA damage was detected by the comet assay.

RESULTSLevels of HSP90 in peripheral blood lymphocytes in three groups were 0.24 +/- 0.32, 0.12 +/- 0.30 and 0.06 +/- 0.33 respectively. They increased significantly compared with that of the control. But levels of HSP60 and HSP27 were not significantly different among those groups. Compared with the control group, there was significant difference in tail length, olive tail moment et al of SCGE (G +/- s(G)) of occupational exposure workers. High-dose group > low-dose group > control group (P < 0.05). The degree of DNA damage increased with the rise of exposure BaP dose (Spearman r = -0.345, P < 0.01).

CONCLUSIONLevels of HSP90 in peripheral blood lymphocytes and the degree of DNA damage increase with the rise of exposure polycyclic aromatic hydrocarbons (PAHs) dose.

Adult ; Chaperonin 60 ; blood ; Coke ; adverse effects ; Comet Assay ; DNA Damage ; drug effects ; HSP27 Heat-Shock Proteins ; blood ; HSP90 Heat-Shock Proteins ; blood ; Humans ; Lymphocytes ; metabolism ; Male ; Occupational Exposure ; adverse effects ; Polycyclic Aromatic Hydrocarbons ; adverse effects

Objective To study the effect of soluble, refolded, recombinant extracellular domain of the human Fc gamma receptor Ⅱ a (huFcγRⅡa) on the binding of human IgG to cells. Methods Extra-cellular domain of the huFcγRⅡ a gene was amplified from recombinant plasmid pe3huR Ⅱ by PCR and then cloned into pET-28a vector. The recombinant plasmid pETshuR Ⅱ was transformed into E. coli BL21 (DE3) after identified by PCR and doubly digested. The inclusion bodies of fusion protein were extracted and purified by washing, dissolved in 6 mol/L guanidine buffer, and refolded by rapid dilution technique. The refolding protein activity was tested by ELISA and flow cytometry. Results Extraceilular domain of the huFcγRⅡa gene was successfully cloned into pET-28a. The results of SDS-PAGE showed that the molecular mass (Mr) of the expressed protein was 24.8 × 103, and the expression rate was 30%. The purity of recom-binant shuR Ⅱ was up to 90% after washing. ELISA showed that the recombinant shuR Ⅱ was able to bind human IgG in a dose dependent manner, shuRⅡ could competitively inhibit the binding of human IgG to huFcγRⅡa expressed on the surface of COS-7 cells by flow cytometry. Conclusion The results demon-strate that it is possible to obtain large quantities of recombinant shuR Ⅱ which has comparable binding prep-erties to those of the whole membrane bound huFcγR Ⅱ a.

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.

OBJECTIVE: To investigate the activation characteristics of microglia (MG) in the rats striatum with MA-induced neurotoxicity. METHODS: Male Wistar rats were divided randomly into control group (n=24) and experimental group (n=24). The rats of experimental group were injected intraperitoneally with MA (15 mg/kg x 8 injections, at 12 hours interval). The rats of control group were administrated with saline. The tissues of striatum of two rat groups were harvested at 0.5 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d and 7 d post initial administrations of MA or saline. The structure changes were observed by transmission electron microscopy and CD-11b immunohistochemistry. The ratio of activated MG was calculated and statistically analyzed. RESULTS: In the control group, the morphological characteristics of the MG showed that the cell bodies were small with slender processes, high electronic density nucleus, and fewer organelles known as the "fork-type". In contrast, the MG in the MA-induced neurotoxicity group displayed larger cell body, shorter cell processes or disappeared, lower electronic density nucleus and rich organelles, resembling "bush-like" or "amoeba-like". The ratio of activated MG in control group was below 0.15 at all timepoints, whereas in the experimental group, the ratio of activated MG increased significantly from day 1 to day 7 (P<0.001). CONCLUSION The continuous MA stimulation of the CNS results in prominent MG activation.
Animals ; Corpus Striatum/pathology* ; Immunohistochemistry ; Male ; Methamphetamine/toxicity* ; Microglia/ultrastructure* ; Microscopy, Electron, Scanning ; Random Allocation ; Rats ; Rats, Wistar ; Staining and Labeling ; Time Factors

OBJECTIVETo study the levels and roles of cytokines TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).

METHODSThe levels of TNF-α, IL-6 and IL-10 in BALF were measured using ELISA in children with MPP at acute stage (n=45) and at remission stage (n=30). Twenty children without lung lesions severed as the control group.

RESULTSThe TNF-α, IL-6 and IL-10 levels in BALF were higher in children with MPP at acute stage than those in the control group (P<0.05). The levels of TNF-α and IL-6 in BALF at remission stage were reduced to the levels similar to the control group and were significantly lower than those at the acute stage in children with MPP. However, the levels of IL-10 in BALF remained at higher levels at remission stage in children with MPP.

CONCLUSIONSThe levels of TNF-α, IL-6 and IL-10 in BALF increase in children with MPP at acute stage, suggesting that the cytokines may be involved in the pathogenesis of MPP.

Adolescent ; Bronchoalveolar Lavage Fluid ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Interleukin-10 ; analysis ; Interleukin-6 ; analysis ; Male ; Pneumonia, Mycoplasma ; etiology ; immunology ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo investigate the effects of polybrominated diphenyl ether-153 (BDE-153) exposure during lactation period on the calcium ion (Ca(2+)) concentration and calcium-activated enzyme levels in cerebral cortical cells among adult rats and to provide a scientific basis for the study on the developmental neurotoxicity of BDE-153.

METHODSForty newborn male rats were randomly and equally divided into four groups according to their body weights and litters: 1, 5, and 10 mg/kg BDE-153 groups and olive oil solvent control group. On postnatal day 10 (PND 10), the BDE-153 groups were administrated BDE-153 (0.1 ml/10 g body weight) by intraperitoneal injection, while the olive oil solvent control group was given an equal volume of olive oil. Two months later, these rats were decapitated, and the cerebral cortex was separated quickly on an ice-cold dish. The Ca(2+) concentration in cerebral cortical cells was measured by flow cytometry. The activities of calcineurin (CaN) and Ca(2+)-Mg(2+)-ATP enzyme were determined by colorimetric method. The mRNA and protein expression of calpain-1 and calpain-2 was measured by real-time quantitative PCR and Western blot.

RESULTSThe mean fluorescence intensities of intracellular Ca(2+) in control group and 1, 5, and 10 mg/kg BDE-153 groups were 10.83, 1.48, 1.93, and 0.62, respectively; the 1, 5, and 10 mg/kg BDE-153 groups had significantly lower intercellular Ca(2+) concentrations than the control group (P < 0.05). The activities of CaN and Ca(2+)-Mg(2+)-ATP enzyme and mRNA and protein expression of calpain-1 showed no significant differences between the 1, 5, and 10 mg/kg BDE-153 groups and control group (P > 0.05). The protein expression of calpain-2 increased as the dose of BDE-153 rose. Compared with the control group (mRNA: 0.81±0.26; protein: 0.15±0.07), the 5 and 10 mg/kg BDE-153 groups had significantly higher mRNA expression of calpain-2 (5 mg/kg BDE-153 group: 1.16±0.52; 10 mg/kg BDE-153 group: 1.32±0.23) and significantly higher protein expression of calpain-2 (5 mg/kg BDE-153 group: 0.31±0.07; 10 mg/kg BDE-153 group: 0.37±0.06) (P < 0.05). The 10 mg/kg BDE-153 group had significantly higher protein expression of calpain-2 than the 1 mg/kg BDE-153 group (0.37±0.06 vs 0.22±0.07, P < 0.05).

CONCLUSIONCa(2+-) mediated calpain-2 activation may be one of the main mechanisms of BDE-153 neurotoxicity.

Animals ; Animals, Newborn ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Calcineurin ; metabolism ; Calcium ; metabolism ; Calpain ; metabolism ; Cerebral Cortex ; metabolism ; Male ; Polybrominated Biphenyls ; toxicity ; Rats ; Rats, Sprague-Dawley