Background The prevalence of hyperuricemia (HUA) among Chinese residents has been increasing annually, with occupational populations facing a higher risk of HUA due to shift work or obesity. Objective To investigate the impact of shift work and obesity on HUA among coal miners, and to provide scientific data for the prevention of HUA in this occupational group. Methods A cross-sectional study was conducted with 25619 workers from a coal mining group in 2023 as the study population, using a questionnaire survey and occupational health check-ups. Workers who were retired or on medical leave, as well as those who provided incomplete responses to the questionnaire or did not complete anthropometric measurements or blood tests, were excluded. A total of 23173 participants were included in the study. An unconditional logistic regression model was used to analyze the association between HUA and selected factors such as shift work status, years of shift work, daily shift work hours, body mass index (BMI), waist-to-height ratio (WHtR), and visceral adiposity index (VAI), as well as the interaction between obesity and shift work on HUA. Restricted cubic spline functions were used to analyze the dose-response relationship between years of shift work, daily shift work hours, and HUA. Results The average age of the included workers was (42.38 ± 9.82) years. A total of 6735 workers reported positive HUA, with a positive rate of 29.1%, and the prevalence was higher in men compared to women (31.8% vs. 13.9%). After adjusting for confounding factors, the restricted cubic spline model revealed a nonlinear dose-response relationship between years of shift work, daily shift work duration, and HUA: ① When the years of shift work exceeded 3.25 years, the risk of HUA in workers gradually increased with longer work duration. At 20 years of shift work, the risk increase showed a "saturation effect," meaning that the risk of HUA no longer increased with additional years of shift work. ② When daily shift work duration was below 10 h, the risk of HUA increased with the length of shift work, but after exceeding 10 h, the risk stabilized. After adjusting for confounding factors, the logistic regression model showed that, compared to non-shift workers, shift workers, those with 10-20 years and over 20 years of shift work experience, as well as those working less than 8 h and more than 8 h per day, had a higher risk of HUA, with odds ratios (OR) of 1.14 (95%CI: 1.06, 1.22), 2.42 (95%CI: 2.20, 2.67), 2.23 (95%CI: 2.00, 2.48), 1.41 (95%CI: 1.29, 1.54), and 1.90 (95%CI: 1.75, 2.06), respectively. Additionally, compared to individuals with normal obesity indices, those with overweight and obesity based on BMI, high and very high VAI and excessive WHtR had a higher risk of HUA, with ORs of 2.01 (95%CI: 1.85, 2.17), 3.51 (95%CI: 3.20, 3.84), 1.42 (95%CI: 1.32, 1.54), 2.10 (95%CI: 1.91, 2.30), and 1.82 (95%CI: 1.69, 1.97), respectively. The interaction analysis showed no interaction between shift work and obesity index (both P_s < 0.001). Conclusion Shift work, longer shift work years, and longer daily shift work hours increase the risk of HUA among coal miners. Additionally, the role of obesity in the development of HUA cannot be ignored.

Background In recent years, the detection rate of thyroid nodules in China's occupational population has shown an upward trend. The prevalence of this disease needs to be taken seriously and targeted measures should be taken to address its influencing factors. Objective To analyze the detection and influencing factors of thyroid nodules among adult male workers in coal mining enterprises in Shanxi Province, and provide a theoretical basis for the prevention of thyroid nodules. Methods A total of 5195 adult male workers from coal mining enterprises who ordered physical examination provided by the Xishan Coal Electricity (Group) Corporation Occupational Disease Prevention and Control Institute in Taiyuan City, Shanxi Province from May 2023 to December 2023 were selected as research subjects. A questionnaire survey, physical examination, ultrasound examination, and biological sample collection and testing were conducted. Thyroid nodules were diagnosed based on ultrasound results, classified and evaluated according to the Chinese-Thyroid Imaging Reporting and Data System (C-TIRADS), and the crude detection rate and standardized detection rate of thyroid nodules in adult male coal mine workers in Shanxi Province wereestimated. Occupational history and occupational exposure information were retrieved from their annual occupational health examination reports provided by the employer. Logistic regression modeling was used to analyze the influencing factors of thyroid nodule. Results A total of 1688 cases of thyroid nodules were detected, with a crude detection rate of 32.49% and an age-standardized detection rate of 31.17%. The cases (constitution ratio) of thyroid nodules by category in the detected cases was as follows: 358 cases (21.21%) were classified as category 2, 1261 cases (74.70%) as category 3, 67 cases (3.97%) as category 4a, and 2 cases (0.12%) as category 4b. The results of logistic regression showed that the duration of exposure to occupational hazards for 11-20 years, 21-30 years, ≥31 years, average monthly working>26 days, and shift work were positively correlated with the detection of thyroid nodules (P<0.05), and the associated ORs (95%CIs) were 1.29 (1.01, 1.65), 1.55 (1.20, 1.99), 1.68 (1.26, 2.55), 1.19 (1.00, 1.40), and 1.15 (1.02, 1.29), respectively. Conclusion The duration of exposure to occupational hazards, average monthly working days, and shift work are influencing factors of thyroid nodules. Intervention measures should be developed based on these influencing factors to prevent the occurrence of thyroid nodules.

Objective To investigate the role of transcription factor EB(TFEB)in endotoxin-tolerant macrophages.Methods The RAW264.7 cells were divided into blank group(DMEM medium),LPS 5 group(5 ng/mL LPS treatment for 4 h),LPS 100 group(100 ng/mL LPS treatment for 4 h),and tolerance group(5 ng/mL LPS for 12 h followed by 100 ng/mL LPS for 4 h).The releases of inflammatory factors TNF-α and IL-6 were measured using ELISA.Western blotting and immunofluorescence assay were used to evaluate the distribution of autophagy-related proteins LC3 and P62,as well as TFEB in the cytoplasm and nucleus.Lentiviral overexpression of TFEB or siRNA-mediated knockdown of TFEB were performed to observe the changes in autophagy levels and bacterial clearance ability in the tolerant cells.Results The cells in the tolerance group had significantly lower contents of TNF-α and IL-6,as well as reduced bacterial clearance ability(P<0.01),down-regulated LC3 expression while up-regulated P62 level,and decreased expression of TFEB in both the cytoplasm and nucleus(P<0.01)when compared with the cells of the LPS 100 group.Overexpression of TFEB significantly increased LC3 level,reduced P62 level,and enhanced bacterial clearance ability in the endotoxin-tolerant cells(P<0.01).In contrast,siRNA-mediated knockdown of TFEB had no significant impacts on LC3 and P62 expression levels or bacterial clearance ability.Conclusion Overexpression of TFEB can restore the autophagy of endotoxin-tolerant cells and enhance their bacterial clearance capacity,thereby alleviating the immunosuppressive state of sepsis.These findings suggest that TFEB holds promise as a potential therapeutic target for the prevention and treatment of sepsis.

Objective To investigate the role and underlying mechanism of activating transcription factor 3(ATF3)in suppressing lipopolysaccharide(LPS)-induced autophagy and inflammatory responses in macrophages.Methods Firstly,the gene expression omnibus(GEO)database was used to analyze ATF3 expression in peripheral blood mononuclear cells(PBMCs)from sepsis patients,and gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways.Secondly,RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group(100 ng/mL LPS).Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization,respectively.Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance.Cleavage Under Targets and Tagmentation(CUT&Tag)sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3.Furthermore,the impact of ATF3 knockdown or overexpression on autophagy-related gene 5(ATG5),autophagy-related gene 16-like 1(ATG16L1),and autophagy levels was evaluated.Results GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients(P<0.01),and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways(P<0.01).In RAW264.7 cells,100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group(P<0.01).ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages(P<0.01),whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases,and remained bacterial clearance at a low level when compared with the conditions in the negative control(NC)group(P<0.01).CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1.Compared with the NC group,ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I,ATG5,and ATG16L1 while decreased p62 expression(P<0.01).Conversely,ATF3 overexpression inhibited the expression of LC3-II/I,ATG5,and ATG16L1(P<0.01),but had no significant effect on p62 level.Conclusion Sepsis induces elevated ATF3 expression in macrophages,and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6,which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1,suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.

Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

To evaluate the advantages of using PBL case library in teaching circulatory system diseases to clinical medicine undergraduate students, a PBL case library was established and applied in teaching practice in the reform of circulatory system teaching. The PBL case library achieved the characteristics of combining theories with cases, morphology with functions, and basic knowledge with clinical knowledge. The PBL case library also realized the informatization, query, and update of cases. Preliminary application showed that the median practical score of students in the case library group was 94.00 points, which was significantly higher than the 92.00 points in the control group ( P=0.005). The average lesson preparation time for teachers in the case library group was (5.00±1.00) hours, which was significantly shorter than the (6.89±0.42) hours in the control group ( P<0.001). The difficulty score for lesson preparation among teachers in the case library group was significantly lower than that of the control group [(1.89±1.05) vs. (3.22±0.44), P<0.001]. However, there were no significant difference in theoretical scores and student satisfaction with teachers and courses. These results suggest that the construction of case library can improve practical teaching effectiveness and enhance the efficiency of lesson preparation for teachers.

Objective:To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection.Methods:From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy.Results:①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion:mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

Objective To observe the clinical efficacy and adverse events of decitabine combined with full_dose and long_term pre_excitation regimen as a induction therapy for relapsed/refractory acute myeloid leukemia (AML). Methods A total of 32 patients with relapsed/refractory AML in Henan Provincial Cancer Hospital from May 2013 to February 2018 were enrolled. All the patients were treated with decitabine combined with full_dose and long_term pre_excitation regimen, including 15 patients who received decitabine combined with CAG regiemtn, and 17 patients who received decitabine combined with CHAG regimen: 25 mg decitabine, intravenous drip, from day 1 to day 3; cytarabine (10-15 mg/m2) administered subcutaneously every 12 h one time, from day 4 to day 17 or more; homoharringtonine (1 mg/m2) intravenous drip, administered intravenously from day 4 to day 10 or more; aclacinomycin (8-10 mg/m2), intravenous drip, administered intravenously from day 4 to day 11 or more; granulocyte colony_stimulating factor (G_CSF) (100-200 μg/m2), subcutaneous injection, and it began 1 day before chemotherapy, adjusted according to the blood cell count; the therapeutic effect and adverse reactions of the patients were observed. Results There were 29 patients (90.6% ) with complete remission (CR), 3 patients (9.4% ) with partial remission (PR), and the overall response (CR+PR) rate was 100.0% (32/32). In decitabine combined with CAG regimen group, 13 patients achieved CR; in decitabine combined with CHAG regimen group, 16 patients achieved CR, and there was no statistically significant difference in the efficacy between the two groups (P＝0.589). The main adverse reactions were agranulocytosis, thrombocytopenia, secondary infection and fever, and no serious adverse events occurred. Conclusion Decitabine combined with full_dose and long_term pre_excitation regimen has a favorable efficacy and safety, which provides a new therapy for relapsed/refractory AML.

Objective: To detect the expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia (B-ALL) in newly diagnosed cases, and to investigate the relationship between CRLF2 and the general clinical characteristics, efficacy and prognosis. Methods: 103 cases of newly diagnosed adult B-ALL patients were investigated from Apr 2016 to Dec 2017 in the Department of Hematology, Henan Cancer Hospital. Bone marrow samples was used to detect the expression of CRLF2 in leukemic cells. The expression of CRLF2 ≥20% was defined as CRLF2-high group and <20% was defined as CRLF2-low group. The clinical characteristics and prognosis of the two groups were compared. Results: The Median overall survival (OS) and disease free survial (DFS) in CRLF2-high group were 9.0 months and 4.25 months, respectively. CRLF2-low group were 15.5 months and 10.25 months, respectively. There was a statistically significant difference in median OS and DFS between the two groups (P=0.007, P=0.000) . The 18-month OS and DFS in CRLF2-high group were 38.6% and 25.1%, respectively. CRLF2-low group were 57.8% and 42.3%, respectively. Multivariate analysis showed high expression of CRLF2 was an independent risk factor for OS (HR=2.991, 95% CI 1.429-6.261, P=0.004) and DFS (HR=2.374, 95%CI 1.146-4.960, P=0.041) in patients. Conclusion Patients with high expression of CRLF2 had poor prognosis.

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.