Objective To investigate the effects of Aurora kinase A(AURKA)on the tumor microenvironment of colorectal cancer(CRC)and to predict the active compounds in Chinese herbs that can target AURKA.Methods Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas(TCGA)database,the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.Results The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues(P＜0.05),and CRC patients with high AURKA expression had shorter overall survival.Compared with the AURKA low-expression group,the abundance of macrophages,monocytes,and effector memory CD4+and CD8+T cells was significantly downregulated in the AURKA high-expression group(P＜0.05).In addition,the cytotoxicity of T cells was significantly reduced(P＜0.05).Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells(MDSCs)and the expression levels of their chemokines CXCL2 and CXCL5(P＜0.05).Genes that were differentially expressed between the AURKA high-and low-expression groups were mainly enriched in monocyte migration,chemokine-induced cellular responses,and other related processes.Chinese herbal compounds,including hesperidin,aristololactam A Ⅱ a,anacardic acid,coumestrol,and 17β-estradiol,all showed binding energies to AURKA lower than-1.2 kcal/mol,indicating a certain level of binding stability.Among these Chinese herbal compounds,17β-estradiol exhibited the best binding stability to AURKA-3UOL.Conclusion The high expression of AURKA in CRC tissues suggests a poor clinical prognosis.AURKA can promote the development of a suppressive immune microenvironment in CRC,and 17β-estradiol,an active compound from Chinese herbs,is a potential therapeutic agent targeting AURKA.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective To evaluate the utility of tuberculosis antibody(TB-Ab),adenosine deaminase(ADA),and carbohydrate antigen 125(CA125)alone or in combination for differentiating tuberculous from non-tuberculous pleural effusion.Methods This retrospective study included 75 patients initially diagnosed with tuberculous pleural effusion(observation group)and 75 patients hospitalized with non-tuberculous pleural effusion(control group)between January 2020 and June 2024.Receiver operating characteristic(ROC)curve analysis was used to compare the diagnostic performance of TB-Ab,ADA,CA125 alone or in combination for diagnosing tuberculous pleurisy.Results The patients with tuberculous pleural effusion showed significantly higher TB-Ab positive rate than the patients with non-tuberculous pleural effusion(control group)(60.00％vs 9.33％,P＜0.001).Tuberculous pleural effusion was associated with significantly higher levels of ADA[(43.44±15.51)U/L]and CA125[(175.57±64.66)U/mL]compared to the control group[(27.81±3.42)U/L]and(122.35±41.22)U/mL,respectively(P＜0.001).Taking 34 U/L as cutoff value,ADA showed good diagnostic performance with an AUC of 0.856,sensitivity of 98.67％,and specificity of 78.67％.Taking 180 U/mL as cutoff value,CA125 demonstrated high sensitivity(89.94％)but low specificity(52.33％)with an AUC of 0.739.CA125 alone was not so specific for detecting tuberculous pleurisy.TB-Ab had an AUC of 0.753 in detecting tuberculous pleurisy,with a sensitivity of 90.67％and specificity of 61.22％.These three markers in combination significantly improved diagnostic performance,with an AUC of 0.926,sensitivity of 90.67％,and specificity of 86.67％.Conclusions TB-Ab,ADA,and CA125 in combination performed better than these biomarkers alone in diagnosing tuberculous pleurisy.

Objective To evaluate the utility of tuberculosis antibody(TB-Ab),adenosine deaminase(ADA),and carbohydrate antigen 125(CA125)alone or in combination for differentiating tuberculous from non-tuberculous pleural effusion.Methods This retrospective study included 75 patients initially diagnosed with tuberculous pleural effusion(observation group)and 75 patients hospitalized with non-tuberculous pleural effusion(control group)between January 2020 and June 2024.Receiver operating characteristic(ROC)curve analysis was used to compare the diagnostic performance of TB-Ab,ADA,CA125 alone or in combination for diagnosing tuberculous pleurisy.Results The patients with tuberculous pleural effusion showed significantly higher TB-Ab positive rate than the patients with non-tuberculous pleural effusion(control group)(60.00％vs 9.33％,P＜0.001).Tuberculous pleural effusion was associated with significantly higher levels of ADA[(43.44±15.51)U/L]and CA125[(175.57±64.66)U/mL]compared to the control group[(27.81±3.42)U/L]and(122.35±41.22)U/mL,respectively(P＜0.001).Taking 34 U/L as cutoff value,ADA showed good diagnostic performance with an AUC of 0.856,sensitivity of 98.67％,and specificity of 78.67％.Taking 180 U/mL as cutoff value,CA125 demonstrated high sensitivity(89.94％)but low specificity(52.33％)with an AUC of 0.739.CA125 alone was not so specific for detecting tuberculous pleurisy.TB-Ab had an AUC of 0.753 in detecting tuberculous pleurisy,with a sensitivity of 90.67％and specificity of 61.22％.These three markers in combination significantly improved diagnostic performance,with an AUC of 0.926,sensitivity of 90.67％,and specificity of 86.67％.Conclusions TB-Ab,ADA,and CA125 in combination performed better than these biomarkers alone in diagnosing tuberculous pleurisy.

Objective To evaluate the noise hazard level of a coal mining enterprise, and identify high-risk operation types and people, and to provide a basis for preventing and controlling the health damage caused by noise. Methods A large coal mining enterprise in Shaanxi Province was selected as the research object. The noise monitoring data of the coal mine over the years was used to calculate the noise exposure matrix of each post in the enterprise, and the classification of occupational hazards at workplaces (GBZ/T 229.4-2012) was used to assess the occupational health risk levels. Results Among the 22 noise-exposed positions in the enterprise, the 8-hour working day equivalent sound level in positions of shearer driver, horseshoe driver, crusher driver, shuttle driver, relaxation screen driver, and grading screen driver were all higher than the occupational exposure limit of noise. In 2021, the noise exposure levels of shearer drivers, crusher drivers, and coal-selecting workers were all higher than 90 dB (A), and the occupational hazard level was moderate hazard level. In addition, the noise exposure levels of most other jobs also exceeded the occupational exposure limit. Conclusion The noise hazards in the coal mine industry are mainly concentrated in the posts of the coal mining system, tunneling system, and screening workshop. Among them, the shearer driver, the crusher driver, and the coal preparation workers have higher noise exposure levels. It is recommended to take corresponding noise reduction measures and strengthen the protection level to reduce the noise exposure risk of workers.

Objective:To analyze effects of tectorigenin on improving cognitive deficits in rats with vascular dementia(VD)by regulating Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods:A total of 72 rats were randomly divided into sham operation group,model group,low,medium and high doses[25,50,100 mg/(kg·d)]tectorigenin groups and positive control group[piracetam 324 mg/(kg·d)],with 12 rats in each group.Except for sham operation group,VD models were replicated in other groups.After successful modeling,different doses tectorigenin groups and positive control group were administered intragastrically with different doses of tectorigenin and piracetam,while other groups were administered intragastrically with same volume of normal saline for 28 d.Spatial learning and memory ability were detected by Morris water maze.Neurotransmitter levels in hippocampus interstitial fluid were detected by high performance liquid chromatography-electro-chemical.Brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor b(TrkB)expressions in hippocampus were detected by RT-qPCR and Western blot.TLR4/MyD88/NF-κB pathway-related proteins in hippocampus were detected by Western blot.Results:Compared with sham operation group,escape latency was longer,while stay time in target area and times of crossing platform were lower in model group(P<0.05).Compared with model group,escape latency was shorter,while stay time in target area and times of crossing platform were higher in medium and high doses tectorigenin groups(P<0.05).NE,DA,5-HT and 5-HIAA levels in model group were lower than those in sham operation group(P<0.05),which were higher in medium and high doses tectorigenin groups than model group(P<0.05).Compared with sham operation group,BDNF and TrkB mRNA and proteins levels were lower,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were higher in model group(P<0.05).Compared with model group,BDNF and TrkB mRNA and proteins levels were higher,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were lower in medium and high doses tectorigenin groups(P<0.05).Conclusion:Tectorigenin can improve cognitive deficits in VD rats,which may be related to regulating TLR4/MyD88/NF-κB signaling pathway.

Objective To detect the expressions of intercellular adhesion molecule-1(ICAM-1)and nu-clear factor(NF)-κB in hepatic tissues of the patients with chronic hepatitis B,and to analyze their correlation with the hepatic inflammatory activity and fibrosis degree.Methods The liver biopsy specimens from 66 pa-tients with hepatitis B and 10 non-hepatopathic controls were selected,and immunohistochemistry and in situ hybridization were used to detect ICAM-1 and NF-κB expression levels in different liver tissues.Results The positive rate of ICAM-1 and NF-κB expression in liver tissues of the patients with chronic hepatitis B was higher than that in normal liver tissues,and the difference was statistically significant(P＜0.05).The expres-sion of ICAM-1 and NF-κB in the patients with hepatitis B was positively correlated with the inflammatory ac-tivity and fibrosis degree(r=0.493,0.496,P＜0.01;r=0.580,0.519,P＜0.01).Conclusion ICAM-1 and NF-κB in the patients with chronic hepatitis B are highly expressed,which is useful in judging the hepatic in-flammatory activity and fibrosis degree.

Objective:To investigate the effects of microRNA (miR) -125b on the proliferation and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway of hepatocellular carcinoma (HCC) cell by targeting Polo like kinases (PLK4).Methods:The tumor tissues and adjacent tissues of 65 patients with HCC were collected from March 2022 to March 2023 in Tianjin Medical University Cancer Hospital, including 33 males and 32 females, aged (60.1±5.6) years. The expressions of miR-125a and miR-125b in liver cancer, adjacent tissues and liver cancer cells were detected by fluorescence quantitative polymerase chain reaction. Low expression liver cancer cell was selected to transfect negative control (NC) sequences of miR, miR-125a and miR-125b. Subsequently, miR-NC and NC plasmid, miR-125b sequence and NC plasmid, and miR-125b sequence and PLK4 plasmid were co-transfected. Cell proliferation was detected by cell counting assay, the expression of PLK4, phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) was detected by Western blot, and miR-125b-targeting PLK4 were detected by bioinformatics analysis and dual luciferase reporter gene.Results:The relative expressions of miR-125a and miR-125b in HCC patients were (0.62±0.08) and (0.58±0.07), respectively, lower than those in adjacent tissues (1.00±0.12) and (1.00±0.13), and the differences were statistically significant ( t=21.24, 22.93, P=0.005, P<0.001). HepG2 cells with low expression of miR-125a and miR-125b and miR-125b targeting PI3K/Akt were selected for transfection. Bioinformatic analysis and dual luciferase reporter gene assay confirmed that miR-125b binds to PLK4. Overexpression of miR-125b could inhibit the proliferation of HepG2 cells and the expression of p-PI3K and p-Akt, while overexpression of PLK4 could partially reverse the proliferation inhibition caused by miR-125b and the expression of p-PI3K and p-Akt, (0.91±0.07) vs(0.41±0.04), (0.97±0.08) vs (0.32±0.03)( t=13.87, 17.01, both P<0.001). Conclusion:The inhibitory effect of miR-125b on HepG2 cell proliferation and PI3K/Akt signaling pathway is partly mediated by targeted inhibition of PLK4.

Objective To estimate the disease burden of silicosis in China from 1990 to 2021 and analyze its changing trend using the data from the Global Burden of Disease Study 2021 (GBD 2021), and to provide evidence for the prevention and control of silicosis. Methods Data on the incidence, prevalence, morbidity and death, mortality and disability-adjusted life year (DALY) of silicosis in China were extracted from the GBD 2021 to analyze the disease burden and age distribution of silicosis. The average annual percentage change (AAPC) was calculated to reflect the temporal trend of various disease burden indicators from 1990 to 2021. The results were then compared with those of the global population. Results In China, prevalent cases of silicosis increased by 116.62% from 79 075 in 1990 to 171 291 in 2021; incident cases of silicosis increased by 75.75% from 13 315 in 1990 to 23 401 in 2021; deaths of silicosis increased by 30.76% from 4 837 in 1990 to 6 326 in 2021; DALYs of silicosis increased by 14.84% from 150,729.65 person-years in 1990 to 173 091.06 person-years in 2021. The age-standardized rate of prevalence, incidence, mortality, DALY, YLL, and YLD of silicosis in China all showed a downward trend. The AAPC (95% CI) was -0.42% (-0.56% ~ -0.29%), -1.02% (-1.16 %~ -0.88%), -2.16% (-2.49% ~ -1.83%), -2.24% (-2.63% ~ -1.84%), -2.45% (-2.76% ~ -2.14%), and -0.42% (-0.54% ~ -0.29%), respectively. From 1990 to 2021, the age-standardized indicators of silicosis in China were all higher than the global level, and the differences were statistically significant (all P <0.05). The proportion of silicosis incident cases in the total incident cases of pneumoconiosis in China increased from 68.49% in 1990 to 78.58% in 2021. Conclusion The age-standardized indicators of silicosis in China showed a downward trend from 1990 to 2021, but the number of prevalent cases, incident cases, and DALYs showed an increasing trend. The age-standardized incident rate of silicosis in China remains at a high level, suggesting that further efforts should be made to prevent and control silicosis.

Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.