Objective To analyze the lung function condition and the prevalence of pulmonary ventilation disorders in the occupational population of Wuhan, and to explore their influencing factors. Methods Physical examination data from the Wuhan Prevention and Treatment Center for Occupational Diseases were used in this study, and finally 9499 people were selected as the study subjects. The linear regression model and logistic regression model were used to analyze the influencing factors of pulmonary ventilation function and pulmonary dysfunction. The restricted cubic spline was used to explore the nonlinear relationship. Results The prevalence of pulmonary ventilation disorders was 1.7%, and the lung function indexes FVC, FEV1, and FEV1/FVC were significantly lower in the population aged >27 years than in the population aged <27 years (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in females than in males (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in underweight occupational groups than in normal-weight groups (P<0.001), and FVC and FEV1 were significantly lower in dust-exposed occupational groups than in groups without dust exposure(P<0.05). Restricted cubic spline plots showed a nonlinear relationship between age and lung function indexes FVC and FEV1 (P_nonlinear< 0.05). Age and BMI were the risk factors for pulmonary ventilation disorders. Conclusion Age, gender, BMI, and dust exposure are risk factors for decreased FVC and FEV1. Age is the risk factor for decreased FEV1/FVC. Age and BMI are the risk factors for pulmonary ventilation disorders.

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*

OBJECTIVES: To develop a heterogeneous graph prediction method based on the fusion of multi-layer semantics and topological information for addressing the challenges in drug-target interaction prediction, including insufficient modeling of high-order semantic dependencies, lack of adaptive fusion of semantic paths, and over-smoothing of node features. METHODS: A heterogeneous graph network with multiple types of entities such as drugs, proteins, side effects, and diseases was constructed, and graph embedding techniques were used to obtain low-dimensional feature representations. An adaptive metapath search module was introduced to automatically discover semantic path combinations for guiding the propagation of high-order semantic information. A semantic aggregation mechanism integrating multi-head attention was designed to automatically learn the importance of each semantic path based on contextual information and achieve differentiated aggregation and dynamic fusion among paths. A structure-aware gated graph convolutional module was then incorporated to regulate the feature propagation intensity for suppressing redundant information and redcuing over-smoothing. Finally, the potential interactions between drugs and targets were predicted through an inner product operation. RESULTS: Compared with existing drug-target interaction prediction methods, the proposed method achieved an average improvement of 3.4% and 2.4%, 3.0% and 3.8% in terms of the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC) on public datasets, respectively. CONCLUSIONS The drug-target interaction prediction method developed in this study can effectively extract complex high-order semantic and topological information from heterogeneous biological networks, thereby improving the accuracy and stability of drug-target interaction prediction. This method provides technical support and theoretical foundation for precise drug target discovery and targeted treatment of complex diseases.
Semantics ; Humans ; Drug Interactions ; Neural Networks, Computer ; Algorithms

To investigate the effect of isthmin-1 (ISM1) on the invasion and metastasis of pancreatic cancer and its underlying mechanism, this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas (TCGA) database. Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines (Aspc1, Bxpc3, PANC1, SW1990) and the pancreatic epithelial cell line (hPNE). Cell models with stable ISM1 overexpression and knockdown were constructed, and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays. Meanwhile, Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition (EMT). Furthermore, TCGA and the Gene Expression Omnibus (GEO) database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis. Immunoprecipitation combined with mass spectrometry (IP-MS) was used to screen for vimentin as an ISM1-binding protein, and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation (Co-IP). Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide (CHX) to detect vimentin protein stability. The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation, thereby enhancing the invasion and metastasis of pancreatic cancer. This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

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 investigate the efficacy and safety of Tubridge flow diverter(TFD)in the treatment of ruptured intracranial aneurysms.Methods The clinical data of 13 patients with aneurysmal subarachnoid hemorrhage,who received TFD treatment at the First Affiliated Hospital of Zhengzhou University between March 2019 and Jul 2022,were retrospectively collected.The perioperative materials and follow-up results were summarized and analyzed.Results Successful operation was accomplished in all the 13 patients(13 aneurysms in total).TFD and coil embolization were simultaneously performed in 10 patients(simultaneous treatment),spring coil filling followed by selective staged TFD placement was adopted in 2 patients(staged treatment),and pure TFD placement was employed in one patient.The incidence of perioperative complications was 15.4%(2/13),including asymptomatic ischemic event in one patient and extra-ventricular drainage-related postoperative bleeding in another patient,which caused death of the patient.The median follow-up time was 6.5 months,and 83.3%of patients(10/12)completed cerebral angiography reexamination with DSA.OKM grade D(complete occlusion of the aneurysm)was obtained in 8 patients(80%),and OKM grade C(residual aneurysm neck)in 2 patients.Conclusion For ruptured intracranial aneurysms,TFD implantation is a clinically feasible treatment with favorable safety and efficacy.

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.

ObjectiveTo explore the relationship between the occupational noise exposure and arteriosclerosis in mechanical manufacturing workers. Methods A total of 453 employees of a machinery manufacturing enterprise were selected as the study subjects using the judgment sampling method. The noise exposure levels in their workplaces were measured, and their cumulative noise exposure (CNE) was assessed based on the type of job-noise exposure matrix and occupational hazard exposure history. Pure-tone audiometry was performed on the research subjects, and their brachial-ankle pulse wave velocity (baPWV) was measured. Results The CNE was (91±11) dB(A) per year and the median baPWV was 1 278.0 cm/s in the research subjects. The results of the generalized linear regression model analysis showed that for every one dB(A) per year increase in CNE, the baPWV of the general population increased by 0.20% ［95% confidence interval (CI) 0.10%-0.30%, P<0.01］, with an increase of 0.17% in males (95%CI 0.06%-0.28%, P<0.01) and 0.28% in females (95%CI 0.07%-0.49%, P<0.01). Using the hearing loss as an outcome indicator for high intensity noise exposure, the results showed that baPWV increased by 7.04% (95%CI 2.42%-11.87%, P<0.01) in individuals with bilateral hearing loss, and by 9.84% and 6.53% (95%CI 3.07%-17.07% and 2.13%-11.11%, all P<0.01) in individuals with elevated high-frequency hearing thresholds in both ears and in either ear, respectively. There was no significant association in elevated speech-frequency hearing thresholds and arteriosclerosis (P>0.05). Conclusion Occupational noise exposure may increase the risk of arteriosclerosis.

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.