Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

OBJECTIVE To establish a method for the determination of plasma protein binding rate of imatinib and its metabolite（N-desmethyl imatinib ）and apply it to patients with gastrointestinal stromal tumor （GIST）.METHODS Using imatinib - d8 as the internal standard ，after being deproteinized methanol ，the sample was determined by equilibrium dialysis combined with liquid chromatography -tandem mass spectrometry . The free concentrations of imatinib and its metabolites in plasma of GIST patients were detected by the same method . RESULTS The protein binding rates of imatinib with albumin ，α1-acid glycoprotein and globulin at 120 ng/mL and 4 000 ng/mL were （92.5±1.0）% and（91.7±0.4）%，（56.6±2.0）% and（62.6±2.6）%，（56.3±3.1）% and （68.0±8.6）% ，respectively. The protein binding rates of N-desmethyl imatinib with albumin ，α1-acid glycoprotein and globulin at 60 ng/mL and 2 000 ng/mL were （90.6±3.5）% and（91.3±1.5）%，（54.1±5.1）% and（63.7±1.3）%，（56.2±7.6）% and（67.5±7.3）%，respectively. Compared with the low concentration group of imatinib （120 ng/mL）and its metabolite （60 ng/mL），the plasma protein binding rate of high concentration of imatinib （4 000 ng/mL）and its metabolite （2 000 ng/mL）with α1-acid glycoprotein and globulin was significantly increased （P＜ Δ基金项目 国家自然科学基金资助项目（No.81503160）；江苏省 0.05），but there was no signifi -cant difference with albumin 卫生健康发展研究中心 2021年度开放课题（No.JSHD2021004）；江苏 （P＞0.05）. In blank plasma ，the protein binding rates of imatinib（4 000 ng/mL）at high concentration and its metabolites（2 000 ng/mL）were significantly lower than those of low （120， 60 ng/mL） and medium （750， 375 ng/mL）concentration （P＜0.01）. Average protein binding rates of imatinib and its metabolite in plasma of GIST patients were （99.0±0.3）% and（99.2±0.3）%，respectively；the correlation coefficients between the concentrations of imatinib and its metabolites and the protein binding rates were －0.298 5 and －3.332 3，respectively（all P＜0.05）. CONCLUSIONS The method for determining the plasma protein binding rates of imatinib and its metabolites is successfully established . The plasma protein binding rates of imatinib and its metabolites in patients with GIST are negatively correlated with drug concentration .

Objective:To analyze the expression of P-selectin and thrombopoietin (TPO) in patients with glioma, and explore their correlation with severity of disease.Methods:One hundred and six patients with glioma who were treated in the Third People's Hospital of Dalian City from June 2017 to June 2019 were selected as the observation group, and 50 physical examination person in the same period were selected as the healthy control group. The clinic data of patients in two groups were analyzed.Results:The serum P-selectin and TPO levels in the observation group were significantly higher than those in the healthy control group: (62.35 ± 16.71) μg/L vs. (25.42 ± 9.18) μg/L, (12.64 ± 3.26) μg/L vs. (6.93 ± 1.77) μg/L ( P<0.01). In patients with different severity of glioma, serum P-selectin and TPO levels in the high-grade group were significantly higher than those in the low-level group: (65.14 ± 17.19) μg/L vs. (53.71 ± 15.26) μg/L, (14.57 ± 3.38) μg/L vs. (9.04 ± 1.97) μg/L ( P<0.01). Serum P-selectin and TPO levels in patients with glioma after treatment were significantly lower than those before treatment: (57.28 ± 16.22) μg/L vs. (62.35 ± 16.71) μg/L, (10.85 ± 2.97) μg/L vs. (12.64 ± 3.26) μg/L ( P<0.01). Spearman correlation analysis result showed that there was a significant positive correlation between serum P-selectin, TPO levels and WHO classification in patients with glioma ( r = 0.417 and 0.361, P<0.05). The results of receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) of serum P-selectin in the diagnosis of glioma was 0.859 (95% CI 0.794 to 0.910, P<0.01), the sensitivity was 90.00%, and the specificity was 74.53%. The ROC curve analysis result showed that the AUC of serum TPO in the diagnosis of glioma was 0.720 (95% CI 0.643 to 0.789, P<0.01), the sensitivity was 69.81%, and the specificity was 72.00%. Conclusions:Serum P-selectin and TPO are abnormally expressed in glioma patients, and their level changes are related to the severity of the disease.

Magnetic manipulation of particles/cells in microfluidic chips is a promising research field.This paper stated the operation mechanism and the main means of manipulation, including separation, concentration, capture, arrangement and assembly.Especially, the concept of particles/cells separation was emphasized with different criteria, like sizes, shapes, and magnetic properties.In addition, the effects of the channel geometry, the intensity and distribution of the magnetic field, and the types of magnetic liquid (paramagnetic salt solutions and ferrofluids) on the performance of the magnetic manipulation were also compared.The prospective to the prospect of magnetic manipulation about particles/cells in microfluidic chip was also depicted.

Objective To explore the protective effect of 17β-estradiol on traumatic brain injury in rats.Methods A total of 45 adult male SD rats were divided into 3 groups using the random digit table, 15 rats in each group:the control group only exposed but not injured the brain, the injury group received traumatic brain injury ( TBI) by Feeney’ s method, and the treatment group received the same handling with injury group, and pretreatment with 17β-estradiol peritoneal injection, 1 mg/kg per day for one week.The other two groups were given the same volume of castor oil.At 6 h, 24 h and 48 h after injury, the brain tissue water content, malondialdehyde ( MDA) content and superoxide dismutase ( SOD) activity were measured.Results At 6 h, 24 h and 48 h after injury, the levels of brain tissue water content in the injury group and treatment group were significantly higher than those in the control group ( P<0.05 ) .At 6 h after injury, the brain tissue water contents in the injury group and treatment group were ( 99.83 ±0.40 )% and ( 99.53 ±0.41 )%,respectively, with a non-significant difference between the two groups (P>0.05).At 24 h and 48 h after injury, the brain tissue water contents in the injury group was ( 105.17 ±0.43 )% and ( 107.54 ±0.39 )%, in the treatment group was (103.26 ±0.42)%and (105.89 ±0.43)%, respectively, showing a significant difference between the two groups ( P<0.05).At 6 h after injury, the levels of MDA in the injury group and treatment group increased and maintained at a higher level, and the levels of SOD decreased.Compared with the control group, there had a significant difference ( P<0.05 ) . The levels of MDA and SOD in the injury group and treatment group at 6 h after injury had a non-significant difference ( P>0.05).But at 24 h and 48 h after injury, the levels of MDA in the treatment group were significantly lower than those in the injury group [(130.39 ±7.02) μmol/g vs.(149.41 ±8.25) μmol/g, (125.41 ±6.59) μmol/g vs.(157.72 ± 8.93) μmol/L] , and the levels of SOD in the treatment group were significantly higher than thoset in the injury group [(88.46 ±7.17) U/g vs.(80.10 ±4.87) U/mg, (97.31 ±7.89) U/g vs.(84.29 ±6.13) U/g], with a significant difference ( P<0.05 ) between the two groups.Conclusions 17β-estradiol has a protective effect on traumatic brain injury.