Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objectives:This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors.Methods:This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.Results:A total of 120 patients developed CRE BSI. Escherichia coli (58/120, 48.3%) was the most prevalent Enterobacteriaceae, followed by Klebsiella pneumoniae (52/120, 43.3%). A total of 93 CRE strains were tested for carbapenemase, of which 75 strains produced carbapenemase (metalloenzyme: 51 strains; serine enzyme: 24 strains). The 30-day mortality rate after BSI was 24.2% (29/120). Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics (7.8% vs 36.2%, P<0.001). Moreover, initiating active therapy within 24 h of BSI onset significantly reduced mortality (15.0% vs 33.3%, P=0.019). The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization (12 h: 14.5% vs 34.1%, P=0.012; 24 h: 40.8% vs 65.9%, P=0.008). Multivariate analysis revealed that septic shock ( HR=24.436, 95% CI 4.148 - 143.966, P<0.001) and pulmonary infection ( HR=9.346, 95% CI 2.718-32.140, P<0.001) were independent risk factors for death within 30 days. Appropriate therapy was initiated within 24 h ( HR=0.225, 95% CI 0.059 - 0.851, P=0.028), and treatment with the ceftazidime-avibactam-containing regimen ( HR=0.082, 95% CI 0.018-0.362, P=0.001) significantly reduced mortality. Conclusion:The prognosis of CRE BSI in patients with hematological diseases is poor. Timely, appropriate therapy and receipt of a ceftazidime-avibactam-containing regimen can improve survival and prognosis.

Objectives:This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors.Methods:This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.Results:A total of 120 patients developed CRE BSI. Escherichia coli (58/120, 48.3%) was the most prevalent Enterobacteriaceae, followed by Klebsiella pneumoniae (52/120, 43.3%). A total of 93 CRE strains were tested for carbapenemase, of which 75 strains produced carbapenemase (metalloenzyme: 51 strains; serine enzyme: 24 strains). The 30-day mortality rate after BSI was 24.2% (29/120). Univariate analysis revealed significantly lower mortality in patients treated with the ceftazidime-avibactam-containing regimen than in those treated with other antibiotics (7.8% vs 36.2%, P<0.001). Moreover, initiating active therapy within 24 h of BSI onset significantly reduced mortality (15.0% vs 33.3%, P=0.019). The proportion of patients with CRE colonization receiving active therapy within 12 and 24 h was significantly higher compared with patients without colonization (12 h: 14.5% vs 34.1%, P=0.012; 24 h: 40.8% vs 65.9%, P=0.008). Multivariate analysis revealed that septic shock ( HR=24.436, 95% CI 4.148 - 143.966, P<0.001) and pulmonary infection ( HR=9.346, 95% CI 2.718-32.140, P<0.001) were independent risk factors for death within 30 days. Appropriate therapy was initiated within 24 h ( HR=0.225, 95% CI 0.059 - 0.851, P=0.028), and treatment with the ceftazidime-avibactam-containing regimen ( HR=0.082, 95% CI 0.018-0.362, P=0.001) significantly reduced mortality. Conclusion:The prognosis of CRE BSI in patients with hematological diseases is poor. Timely, appropriate therapy and receipt of a ceftazidime-avibactam-containing regimen can improve survival and prognosis.

Ulcerative colitis （UC） is a common inflammatory bowel disease （IBD） in clinical practice， characterized by symptoms such as abdominal pain， diarrhea， and bloody mucus in the stool. It is difficult to cure and has a high recurrence rate. The pathogenesis of UC is related to abnormal immune response， oxidative stress in intestinal tissues， and inflammatory reactions. As reported， the abnormal activation of the NOD-like receptor pyrin domain-containing protein 3 （NLRP3） inflammasome is involved in the pathological process of UC. This activation triggers pathological mechanisms such as oxidative stress， pyroptosis， and inflammation in intestinal epithelial cells. Therefore， blocking the abnormal activation of NLRP3 is beneficial for alleviating UC. Currently， western medicine treatment for UC mainly includes salicylic acid derivatives， corticosteroids， and biologics， but the overall efficacy is unsatisfactory. Traditional Chinese medicine （TCM） treatment of this disease has the advantages of significant efficacy and low recurrence rate. In recent years， great advances have been made in the basic research of using TCM methods to treat UC. Studies have found that TCM intervention targeting the NLRP3 inflammasome can significantly promote intestinal mucosal healing and treat UC， and the mechanism of action involves multiple targets， levels， and pathways. This article summarized the experimental research on the impact of TCM targeting the NLRP3 inflammasome on UC in recent years， and found that NLRP3 interacted with factors such as Caspase-1 and nuclear factor-κB （NF-κB）， thereby promoting the release of pro-inflammatory factors and cell pyroptosis in intestinal epithelial cells. This activation triggered oxidative stress， inflammatory reactions， and other pathological mechanisms. TCM acted on the NLRP3 inflammasome and its upstream and downstream factors to block the pathological process of UC， inhibit the pathological damage to the intestinal mucosa， and thereby alleviate colonic ulcers. The findings of this study provide a theoretical basis for the prevention and treatment of UC and further drug development.

Objective:To analyze the mediastinal displacement of target volume in the postoperative radiotherapy (PORT) process for non-small cell lung cancer (NSCLC) and the value of mid-term evaluation.Methods:For 100 patients with postoperativeN 2 stage NSCLC, R 1-2 and any N staging, bone anatomy was utilized to measure the change of the first and second CT localization on the same level. Statistical analysis were performed using the WilCoxon, Kruskal-Wallis and χ2 tests. The cut-off values were calculated with the receiver operating characteristic (ROC) curve. Results:Among the included patients, in the PORT process, the mediastinal displacement in the x (front and rear), Y (left and right) and Z (upper and lower) directions were 0.04-0.53 cm, 0.00-0.84 cm and 0.00-1.27 cm, respectively, and the order of mediastinal displacement distance wasz > Y> X,respectively. According to the ROC curve calculation, the cut-off values were 0.263, 0.352 and 0.405, respectively, which were greater than the cut-off values in 25 cases (25%), 30 cases (30%) and 30 cases (30%), respectively. There was significant difference in the three-dimensionalmediastinal displacement ( P=0.007, <0.001 and<0.001). The mediastinal displacement in thex, Y and Z directions had no statistical significance regarding resection site ( P=0.355, 0.239 and 0.256) and operation mode ( P=0.241, 0.110 and 0.064). Comparative analysis of modified whole group mediastinal shift> and cut-off values, medium-simulation (m-S) and the originally planned radiotherapy shown that there was no significant difference in the incidence of radiation esophagitis (RE) and radiation pneumonitis in PORT patients (all P>0.05); however, the incidence of ≥grade 3 RE in the modified plan after m-S was significantly lower than that in the originally planned PORT patients, which were 0 and 7%, respectively ( P<0.001). Conclusions:Mediastinal displacement exists in the PORT process of N 2 or/and R 1-2 cases after radical operation of NSCLC, and obvious movement occurs in 20%-30% of patients. Relocating and modifying the target volume and radiotherapy plan in the middle of the PORT process is beneficial to quality assurance and quality control.

OBJECTIVE To study different extraction fractions of Agrimonia pilosa against h epatic fibrosis. METHODS Using hepatic stellate cells HSC-T 6 of rats as objects ，the effects of different extraction fractions （total extract ，ethyl acetate fraction ， petroleum ether fraction and n-butanol fraction ）with different concentrations （0.5，5，50，500，5 000 μg/mL，calculated by raw drug）of A. pilosa on the proliferation of HSC-T 6 cells were detected （after treated for 24，48，72 h）；median inhibition concentration（IC50）was also caculated. Platelet-derived growth factor （PDGF-BB）was used to induce the activation of HSC-T 6 cells to establish hepatic fibrosis cell model. Flow cytometry was used to detect the effects of different extraction fractions of A. pilosa on apoptosis of HSC-T 6 cells. The expression of collagen Ⅰ（Col-Ⅰ）in the supernatant was detected by enzyme linked immunosorbent assay. The expressions of α-smooth muscle actin （α-SMA），Col-Ⅰ，B-cell lymphoma- 2（Bcl-2），Bcl-2-associated X protein （Bax）and caspase- 3 were detected by Western blot assay. RESULTS Total extract ，ethyl acetate fraction ，petroleum ether fraction and n-butanol fraction of A. pilosa could significantly increase the apoptotic rate of HSC-T 6 cells（P＜0.01）. After treated for 24 h，IC50 of above fractions were 50.17，20.75，5.82，4.09 μg/mL，respectively. After intervened with PDGF-BB ，the expression of Col- Ⅰ in supernatant of HSC-T 6 cells as well as protein expression of Col- Ⅰ，α-SMA，Bcl-2，Bax and caspase- 3 in HSC-T6 cells were increased significantly （P＜0.01）. After intervened with different extraction fractions of A. pilosa ，most of the expressions of above proteins in HSC-T 6 cell culture supernatant or cells were significantly reversed compared with PDGF-BB group （P＜0.05 or P＜0.01）， and the intervention effect of n-butanol fraction of A. pilosa was the most significant. CONCLUSIONS Different extraction fractions of A. pilosa can inhibite the proliferation of HSC-T 6 cells and induce their apoptosis；n-butanol fraction from A. pilosa may be an effective fraction to exert the effect of anti-hepatic fibrosis.

OBJECTIVE: To investigate the effects of over-expression of miR-144 on invasion of SMMC-7721 cells and Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway in hepatocellular carcinoma cells. METHODS: The expressions of miR-144 was examined in normal human hepatocyte line HL-7702 and hepatocarcinoma cell line SMMC-7721 using realtime quantitative PCR (qRT-PCR). SMMC-7721 cells were divided into blank group, miR-144 NC group and miR-144 mimics group, and the expressions of miR-144 in each group were detected with qRT-PCR. Cell count kit-8 (CCK8) was used to assess the survival of SMMC-7721 cells, and the cell invasion was evaluated using Transwell assay. The expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and TLR/MyD88 pathway-related proteins in the cells were detected with Western blotting; the effect of 40 μ mol/L MyD88 inhibitor on TLR/MyD88 pathway-related proteins was examined in SMMC-7721 cells. RESULTS: Compared with normal human hepatocytes, SMMC-7721 cells expressed a significantly lower level of miR-144 ( < 0.05). CCK-8 assay showed that test showed that miR-144 over-expression significantly decreased the cell survival rate ( < 0.05), lowered the number of invasive cells, and decreased the expression of MMP-2 and MMP-9 in SMMC-7721 cells ( < 0.05). The expressions of Toll-like receptor 4 (TLR4), MyD88, phosphorylated nuclear factor-kappa B (pNF-κB) and NF-κB protein decreased significantly in miR-144 mimics group and TJ-M2010-2 group ( < 0.05) and were comparable between the two groups ( > 0.05). CONCLUSIONS Overexpression of miR-144 decreases SMMC-7721 cell survival and invasion by inhibiting TLR/MyD88 pathway.
Cell Line, Tumor ; Humans ; Liver Neoplasms ; Matrix Metalloproteinase 2 ; MicroRNAs ; Myeloid Differentiation Factor 88 ; NF-kappa B ; Signal Transduction ; Toll-Like Receptors