Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of elderly patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of elderly DLBCL patients diagnosed pathologically between 2010 and 2015 were extracted from the SEER database. Cox proportional hazards model was used for multivariate analysis, and Kaplan-Meier survival curves were plotted to explore the prognostic factors affecting overall survival (OS). RESULTS: A total of 11 523 elderly DLBCL patients were included, of whom 58.6% had stage Ⅲ/Ⅳ disease, and 28.8% exhibited extranodal involvement. Besides lymph nodes (68.5%), common primary extranodal sites included the gastrointestinal tract (9.8%) and lip, mouth, and pharynx (4.1%). The median survival time for the entire cohort was 47 months, with a 3-year survival rate of 52.0%, and a 5-year survival rate of 47.8%. Multivariate Cox regression analysis revealed that age, sex, race, Ann Arbor stage, primary site, B symptoms, treatment modality, treatment sequence, and whether DLBCL was the first malignant primary indicator were independent prognostic factors affecting OS in elderly DLBCL patients (all P <0.05). CONCLUSION Age≥70 years, male, black race, advanced Ann Arbor stage, primary sites in the lungs, liver, or kidney, presence of B symptoms, and preoperative systemic therapy were independent risk factors for poor prognosis in elderly DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Prognosis ; Aged ; Male ; Female ; Survival Rate ; Proportional Hazards Models ; Aged, 80 and over ; Kaplan-Meier Estimate ; Neoplasm Staging

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

Objective: To investigate the effect and mechanism of methyltransferase-like3(METTL3),which functions as m6A modification methyltransferase,on the cellular proliferation,clone formation and migration of nonsmall cell lung cancer(NSCLC) cells. Methods: The METTL3 level and patient overall survival were analyzed by bioinformatics.In the transfected A549 cells,the expression of METTL3 was detected by RT-PCR and Western blot assays,the m6A level was detected by m6A RNA Methylation Assay kit,the cellular viability and growth were detected by CCK-8 assay,the apoptosis was detected by immunofluorescent assay,the colony growth was detected by clone formation assay,the cell migration growth was detected by scratch. Results : Bioinformatics showed that METTL3 was highly expressed in NSCLC and negatively correlated with patient overall survival.The RT-PCR and Western blot data showed that the METTL3 level was higher in NSCLC cells.Moreover,higher METTL3 significantly promoted m6A level,cell proliferation,colony formation,migration,inhibited cell apoptosis,increased the mRNA and protein expressions of EMT-related marker Vimentin but inhibited apoptosis and decreased the mRNA and protein expressions of EMT-related marker E-cadherin in the A549 cells.Furthermore,the contrasting results were obtained in the A549 cells with the knockdown of METTL3. Conclusion The over-expressed METTL3 increases the m6A levels in NSCLC cells and promotes cellular proliferation,colony formation,and migration growth,thereby laying a theoretical foundation for future research on early diagnosis and targeted drug development for NSCLC by targeting METTL3.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

ObjectiveTo explore the compliance related factors of repeated screening for colorectal cancer in Jiading District， and to provide a scientific basis for the prevention and control of colorectal cancer. MethodsBased on the natural population cohort in Jiading District， and the screening situation in 2017‒2019 and 2020‒2022， the study subjects were divided into the groups of never participating in screening and participating in screening. Subjects in the participating group were further divided into participating in one round of screening or having repeated screening. SPSS 21.0 software was used to analyze the demographic characteristics of each group. χ² test or Fisher precise probability test were used to conduct univariate analysis of the factors such as gender， age， education level， marital status， retirement status， and type of medical insurance. Factors with the significant difference （P<0.05） were selected for inclusion in multivariate analysis， and factors related to compliance with repeated screening were analyzed by multivariate logistic regression. ResultsA total of 8 179 subjects were included in the study， including 3 323 males （40.6%） and 4 856 females （59.4%）. The average age of the subjects was （61.26±6.06） years old. A total of2 652 （32.4%） had educated in primary school or below， 4 242 （51.9%） in secondary school， and 1 285 （15.7%） in higher secondary school. Mostly， 7 579 （92.7%） were married. Among the participants， 4 062 people had never participated in screening， 4 117 people had participated in screening， and 1 485 of them had repeated screening， with a repeated screening rate of 18.2%. Multivariate logistic regression analysis showed that women had better compliance with repeated screening than men （OR=1.31， 95%CI： 1.14‒1.50）. Compared with the population aged 50 to 54 years， the population aged 55‒59 years （OR=1.57， 95%CI： 1.19‒2.08）， 60-64 years （OR=2.77， 95%CI： 2.13‒3.61）， and 65-69 years （OR=3.31， 95%CI： 2.51‒4.36） had higher compliance with repeated screening. Compared with employees' medical insurance， residents' medical insurance group had worse compliance with repeated screening （OR=0.76， 95%CI： 0.66‒0.87）. People with a history of intestinal polyps were more likely to undergo repeat screening than those without （OR=2.07， 95%CI： 1.50‒2.87）. ConclusionCompliance with repeated screening for colorectal cancer still needs to be improved， and there are differences in compliance with repeated screening for different populations with different characteristics. Identifying groups that are unlikely to adhere to community-based colorectal cancer screening and taking targeted interventions can help improve the continued compliance of residents with colorectal cancer screening.