ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g^-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.

Objective:To explore the impact of multimorbidity on disability in older adults, providing a reference for formulating strategies for the management and nursing of multimorbidity and disability in older adults.Methods:Adopting the method of cross-sectional survey research, the data of 6 469 older adults (≥60 years old) were collected from the 2018 Chinese Longitudinal Healthy Longevity Survey database in July 2023, including basic information, chronic disease prevalence, and disability measured by basic activities of daily living (BADL), and instrumental activities of daily living (IADL). They were divided into multimorbidity and non-multimorbidity groups based on whether they had two or more chronic diseases. The propensity score matching (PSM) method was used to match the basic conditions of the two groups of older adults with the proportion of 1∶1. Binary logistic regression was applied to analyze the effects of multimorbidity on BADL disability and IADL disability.Results:Among 6 469 older adults, there were 2 882 males and 3 582 females, with 3 158 aged 60-84 years old and 3 311 aged over 84 years old. BADL disability accounted for 26.5% (1 712/6 469), while IADL disability accounted for 66.8% (4 324/6 469). There were 2 335 patients in the multimorbidity group and 4 134 patients in the non-multimorbidity group. Binary Logistic regression analysis showed that the risk of BADL disability in older adults in multimorbidity group was 1.511 times higher than that in the non-multimorbidity group (95% CI 1.317-1.734, P<0.01); the risk of IADL disability in older adults in the multimorbidity group was 1.618 times higher than that in the non-multimorbidity group (95% CI 1.426-1.835, P<0.01). Conclusions:Multimorbidity would increase the risk of disability in older adults. Relevant authorities should develop relevant interventions and nursing responses to enhance the prevention and management of multimorbidity and disability in older adults.

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 explore the association of different obesity measurement indexes on serum C-reactive protein (CRP) in Chinese adult women.Methods:The data were obtained from baseline and follow-up surveys of the urban Breast Cancer Screening Program in Shuangliu District, Chengdu. A total of 441 adult women were included in the study. A questionnaire survey, physical examination, and laboratory testing were conducted on the subjects. Multivariate logistic regression model, two-level mixed effects logistic regression model, and restricted cubic spline method were used to investigate the linear and nonlinear correlation between different obesity measurement indexes and serum CRP in adult women.Results:For every 1 unit increase in BMI, waist circumference (WC), and adiposity, the risk of elevated serum CRP or exacerbation of chronic low-grade inflammation in adult women increased by 16.5%, 5.0%, and 11.1% ( P<0.05), respectively. Both BMI and adiposity were nonlinear correlated with serum CRP. Using BMI=24.0 kg/m 2 as the reference point, serum CRP level increased with the increase of BMI when BMI >24.0 kg/m 2. Using adiposity=30% as the reference point, serum CRP level increased with the increase of adiposity when adiposity >30%. Conclusions:Overall, obesity reflected by BMI had the strongest association with serum CRP in adult women, followed by body fat content reflected by adiposity, and central obesity reflected by WC had the weakest association with CRP. Adult women with BMI >24.0 kg/m 2 or adiposity >30% are at high risk for obesity-related inflammatory manifestations.

Semiconductor quantum dots (QDs) are a new kind of biological fluorescence material, which has many advantages, such as broad excitation spectra, tunable emission spectra and good photostability. In the field of biomedical detection, the problems encountered in the traditional organic dye-based biomedical detections, such as short fluorescence lifetime and failure to simultaneous excitation of multiple colors, can be solved by using QDs. Water-soluble QDs combined with specific bio-molecules can label targeting bio-compound, which is useful in bio-molecule detection, cell labeling, tissue imaging, and can be used in fluorescence resonance energy transfer (FRET) technology. Combining QDs and protein chip technology to develop a new technology to detect multiple kinds of tumor markers will be one of the promising clinical applications of QDs with greater sensitivity, specificity, rapidity and convenience.
Animals ; Biomarkers, Tumor ; analysis ; Fluorescence Resonance Energy Transfer ; methods ; Humans ; Protein Array Analysis ; Quantum Dots ; Sensitivity and Specificity

Quantum dots, as a new kind of biological fluorescence material, have properties superior to the traditional organic dyes. In the recent decade, researches about the application of quantum dots in biomedicine have made great progress. Tumor markers have vital importance in the diagnosis and treatment of carcinoma; however, they are not widely used for lack of specificity and sensitivity. Researches about applications of quantum dots in the detection of tumor markers are centralized in three aspects, namely the detection of serum/plasma tumor markers, the detection of tissue and cell tumor markers (such as molecular imaging of cell and tissue), and the detection of tumor in vivo animals. A combination of quantum dots and flow cytometry technique for developing a new technique to detect multiple kinds of tumor markers at the same time with greater sensitivity, specificity, rapidity and convenience may have the potential for clinical use of quantum dots.
Biomarkers, Tumor ; analysis ; Humans ; Quantum Dots