Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

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 understand the epidemiological characteristics of central obesity and pre-central obesity and influencing factors in residents in Jilin Province, and provide reference for the prevention and control of central obesity and pre-central obesity.Methods:Based on the results of early screening and comprehensive intervention program in high-risk groups of cardiovascular disease in Jilin dyring 2017-2018, a total of 11 903 participants aged 35-75 years in 6 project areas in Jilin were included as the survey subjects for physical examination, laboratory test and questionnaire survey. The prevalence of central obesity and pre-central obesity in populations with different characteristic and health status were analyzed by χ2 test, trend χ2 test, F-test. Multivariate logistic regression model was used for influencing factor analysis. Results:The central obesity rate was 33.35% (3 970/11 903), the standardized rate was 31.73%, the pre-central obesity rate was 28.79% (3 427/11 903), the standardized rate was 28.86%. Multifactor analysis results showed that being rural resident ( OR=1.99, 95% CI: 1.78-2.23), being woman ( OR=1.76, 95% CI: 1.57-1.97), 65-75 years old ( OR=1.21, 95% CI: 1.03-1.45), senior high school and technical secondary school education level ( OR=1.38, 95% CI: 1.17-1.63), annual family income >100 000 yuan ( OR=1.65, 95% CI: 1.20-2.26), overweight ( OR=9.27, 95% CI: 8.26-10.41), obesity ( OR=82.82, 95% CI: 62.63-109.52), normal high blood pressure ( OR=1.49, 95% CI: 1.27-1.74), hypertension ( OR=1.70, 95% CI: 1.42-2.04), diabetes ( OR=2.30, 95% CI: 1.94-2.73), dyslipidemia ( OR=1.33, 95% CI: 1.18-1.50) were positively related to the risk for central obesity and pre central obesity. Conclusions:The prevalence rates of central obesity and pre central obesity in residents in Jilin were at high levels, being rural resident, being woman, older age, senior high school and technical secondary school education level, high income, overweight and obesity, normal high blood pressure and hypertension, diabetes, dyslipidemia were risk factors for central obesity and pre-central obesity in Jilin.

Objective:To identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.

Objective : To investigate the effect of sinomenine on proliferation and migration of multiple myeloma (MM) cells by regulating STAT3 and NF-κB signaling pathway． Methods : The cultured U266 cells were treated with different concentrations of sinomenine (0，0．5，1，2 mmol / L) ．The control group was added DMSO with 0．5% concentration．CCK-8 assay was used to detect the proliferation of U266 cells．Flow cytometry was used to detect the apoptosis of U266 cells．Western blot assay was used to detect the expression levels of apoptosis-related proteins， STAT3 and NF-κB signaling pathway proteins in the each group. Results : Compared with CON group，the apopto- sis of U266 cells increased after Sinomenine treatment，the proliferation was inhibited ; B lymphoma-2 (Bcl-2) mye- loid and cell leukemia-1 (Mcl-1) expression level decreased ; activated Caspase-3 (cleaved Caspase-3) and PARP (Cleaved Caspase-3) expression levels increased ; the activity of STAT3 and NF-κB signaling pathway decreased. Conclusion Sinomenine can down-regulate the activity of STAT3 and NF-κB signaling pathway，promote the apop- tosis of U266 cells and inhibit the proliferation of U266 cells.

Objective : To detect the low⁃affinity penicillin⁃binding protein drug resistance , pbp4 gene , and multi⁃ locus sequence typing (MLST) of clinically isolated E. faecalis . Methods : 78 clinical isolates of E. faecalis were collected , and their drug resistance was detected by automated instruments ; the mutation of pbp4 gene mutation was analyzed by PCR amplification and MLST . Results : 78 strains of E. faecalis were highly resistant to ciprofloxacin , levofloxacin , rifampicin , erythromycin , tetracycline and high concentration of gentamicin , and were resistant to penicillin and gentamicin . The ampicillin resistance rate was 10. 3% , and no strains were found to be resistant to nitrofurantoin , vancomycin , teicoplanin and linezolid ; 8 strains of 78 E. faecalis had amplified TEM genes , and all of them were resistant to penicillin and ampicillin resistance , with a positive rate of 10. 3% ; the allelic profiles and sequence types of 78 strains of E. faecalis which were divided into 16 sequence types , of which ST179 and ST16 were the most , with 21 and 21 strains , respectively . 20 strains , accounting for 26. 9% and 25 . 6% , the rest were ST6 type 8 strains (10. 3% ) , ST4 type 7 strains (9 . 0% ) , ST585 type 6 strains (7 . 7% ) , ST480 type 4 strains (5 . 1% ) , ST28 strains 3 strains (3 . 8% ) of the ST type were detected , and only 1 strain was detected for the oth⁃ er ST types . The analysis of the relationship between ST types and drug resistance showed that E. faecalis with the same ST type had similar drug resistance profiles . Conclusion The resistance mechanism of E. faecalis to β ⁃lactam antibiotics is mainly caused by the production of β⁃lactamase mediated by TEM gene , which is not necessarily related to the mutation of pbp4 gene . The isolates of E. faecalis are mainly CC16 ( including ST16 and ST179) clones and drug resistance is serious . It is necessary to guide clinical medication and strengthen nosocomial infection monitoring according to its characteristics .

OBJECTIVE To evaluate the qualit y of Xihuang pills ，and to screen the differential markers affecting its quality . METHODS Using muskone as internal reference ，the content of α-pinene and other 4 components were determined by quantitative analysis of multi -components by single marker （QAMS），and compared with the results of external standard method . The fingerprints of 13 batches of Xihuang pills were established by gas chromatography （GC）method. Cluster analysis （CA）and orthogonal partial least squares discriminant analysis （OPLS-DA） were performed by SPSS 25.0 software and SIMCA 14.1 software. The variable importance projection （VIP）value greater than 1 was used as the standard to screen differential markers affecting the quality of the samples . RESULTS The contents of α-pinene，octyl acetate and β-elemene measured by QAMS were 0- 0.628 4，0.378 0-2.679 4 and 0.320 9-0.815 4 mg/g，respectively. The contents of α-pinene，octyl acetate ，β-elemene and musk ketone measured by external standard method were 0.001 5-0.627 1，0.378 0-2.594 7，0.329 2-0.837 0 and 0.385 7-0.806 0 mg/g， respectively. The relative error of the content determination results of the two methods was less than 4%. There were 26 common peaks in 13 batches of Xihuang pills ，and 3 common peaks ，such as octyl acetate ，β-elemene and musk ketone ，were identified ； their similarities were 0.912-0.946. 13 batches of samples could be divided into two categories （S1-S2，S6-S10，S13 were clustered into one category and S 3-S5，S11-S12 were clustered into one category ）. VIP values of peak 7，11，10，17 and 16 were all greater than 1. CONCLUSIONS The content of 4 components such as α-pinene in Xihuang pills combined with GC fingerprint and chemical pattern recognition analysis can be used to evaluate the quality of Xihuang pills . The components corresponding to 5 common peaks such as peak 7 may be differential markers affecting the quality of the samples .