ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Objective To prepare a multifunctional mesoporous silica-based nanocarrier system(MMSN@Gem)with gemcitabine and investigate its effect on bladder cancer cells BIU-87.Methods The multifunctional meso-porous silica-based nano drug-carrying system was prepared by a modified method.Transmission electron microsco-py,high-performance liquid chromatography,and thermal imaging were used to characterize the morphology,drug-carrying and photothermal properties of MMSN@Gem.The effect of MMSN@Gem on BIU-87 bladder cancer cells was detected by in vitro experiments.Results MMSN@Gem exhibited a well-defined spherical morphology with an average particle size of(102.48±1.03)nm with a drug loading capacity of 25.04％±0.17％,and an average zeta potential of(-24.84±0.07)mV.The photothermal conversion efficiency was 40.7％which significantly enhanced the release of Gem under near-infrared irradiation.In vitro studies showed that MMSN@Gem significantly inhibited BIU-87 cell activity,induced apoptosis of BIU-87 cells,reduced migration and invasion ability,and enhanced its uptake by BIU-87 cells.Conclusions MMSN@Gem exhibits excellent photothermal properties,enhances cellular uptake efficiency,inhibits the proliferation and migration of BIU-87 cells,and promotes apoptosis,providing a promising drug delivery system for the clinical treatment of bladder cancer.

Objective To explore the changes of serum angiopoietin-like protein 4(ANGPTL4)and NOD-like receptor protein 3(NLRP3)levels after traumatic brain injury(TBI)and their diagnostic value for sec-ondary massive cerebral infarction.Methods A total of 100 TBI patients admitted to the hospital from Au-gust 2019 to August 2021 were enrolled as the TBI group,meantime,100 healthy people in the hospital were enrolled as the control group.The serum levels of ANGPTL4 and NLRP3 were detected by enzyme-linked im-munosorbent assay(ELISA).The clinical characteristics of TBI patients with and without secondary massive cerebral infarction were compared.Receiver operating characteristic(ROC)curve was applied to analyze the serum levels of ANGPTL4 and NLRP3 on their diagnostic value for TBI patients with secondary massive cere-bral infarction.Multivariate Logistic regression analysis was applied to analyze the factors affecting the occur-rence of secondary massive cerebral infarction in TBI patients.Results The serum ANGPTL4 level in TBI group was lower than that in the control group,and the serum NLRP3 level was higher than that in the con-trol group(P<0.05).There were obvious differences in proportion of brain hernia,proportion of subarach-noid hemorrhage,serum levels of ANGPTL4 and NLRP3 between patients with secondary massive cerebral infarction and patients without secondary massive cerebral infarction(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum ANGPTL4 and NLRP3 in diagnosing secondary massive cere-bral infarction in TBI patients was 0.792 and 0.812 respectively,with sensitivity of 77.80%and 83.30%re-spectively,and specificity of 86.60%and 64.60%respectively.The sensitivity,the specificity and AUC of the combined detection were 83.30%,82.90%and 0.867 respectively.Multivariate Logistic regression analysis showed that serum NLRP3 level was a risk factor for TBI patients with secondary massive cerebral infarction(P<0.05).After treatment,it was found that serum ANGPTL4 level increased and NLRP3 level decreased in TBI patients(P<0.05).Conclusion The serum level of ANGPTL4 in TBI patients decreases,while the level of NLRP3 increases,and the level of ANGPTL4 in the serum of patients with secondary massive cerebral in-farction decreases and the level of NLRP3 increases,both of them are of great significance in the diagnosis of secondary massive cerebral infarction in TBI patients.

Objective To analyze the occupational health status of radiation workers in Guangdong Province. Methods A total of 8 913 radiation workers who underwent occupational medical examination (OME) in Guangdong Province Hospital for Occupational Disease Prevention and Treatment in 2020 were selected as the exposure group, and 2 024 non-radiological workers who underwent health examination in the same hospital in the same period of time were selected as the control group using convenient sampling method. The study analyzed the prevalence of abnormalities in thyroid, eye lens, blood pressure, complete blood count and micronucleus in individuals of the two groups. Results The abnormal rates of eye lens, blood pressure and complete blood count in the radiation workers in the exposure group were higher than those in the control group (23.3% vs 8.0%, 18.6% vs 9.0%, 18.1% vs 8.5%, all P<0.01). However, there was no significant difference in the abnormal rates of thyroid and micronucleus in workers between these two groups (12.8% vs 11.5%, 0.1% vs 0.0%, all P>0.05). The abnormal rates of thyroid, eye lens and blood pressure in radiation workers increased with the exposure period of radiation (all P<0.05). Conclusion Long-term exposure to low-dose ionizing radiation have certain effects on the thyroid, eye lens, and blood pressure of radiation workers, with a time-effect relationship of years of radiation work.

Objective To investigate the predictive value of Rotterdam CT score combined with serum soluble cluster of differentiation antigen 40 ligand (sCD40L) and fibulin-5 for prognosis of patients with severe traumatic brain injury (sTBI). Methods A total of 186 sTBI patients were divided into good prognosis group (n=104) and poor prognosis group (n=82). CT images were analyzed and Rotterdam CT scores were obtained; the enzyme-linked immunosorbent assay (ELISA) was used to detect serum sCD40L and fibulin-5 levels on the 1st, 3rd and 7th day of admission; the Spearman analysis was used to assess the correlations of serum sCD40L and fibulin-5 levels on the first day of admission with the Rotterdam CT score and Glasgow Coma Scale (GCS) score; the Multivariate Logistic regression analysis was conducted to explore the risk factors for poor prognosis in sTBI patients; the receiver operating characteristic (ROC) curve was performed to analyze the predictive value of Rotterdam CT score combined with serum sCD40L and fibulin-5 levels on the first day of admission for prognosis of sTBI patients. Results On the 1st, 3rd and 7th day of admission, compared with the good prognosis group, the serum levels of sCD40L and fibulin-5 in the poor prognosis group were significantly elevated (P < 0.05); serum sCD40L and fibulin-5 levels were negatively correlated with GCS scores (r=-0.505, -0.421, P < 0.05) and positively correlated with Rotterdam CT score (r=0.495, 0.397, P < 0.05); sCD40L (OR=2.768, 95%CI, 1.537 to 4.983) and fibulin-5 (OR=2.539, 95%CI, 1.301 to 4.953) were independent risk factors for poor prognosis in sTBI patients (P < 0.001); the area under the curve (AUC) of Rotterdam CT score combined with serum sCD40L and fibulin-5 levels on the first day of admission for predicting poor prognosis in sTBI patients was 0.969 (95%CI, 0.933 to 0.989), with a sensitivity of 86.59% and a specificity of 94.23%; the diagnostic performance of Rotterdam CT score combined with sCD40L and fibulin-5 was superior to that of each individual indicator (Z=4.233, 4.274, 4.433, P < 0.001); the Bootstrap internal validation results showed that the predictive performance curve of the combined prediction model was consistent with the actual clinical occurrence curve. Conclusion Rotterdam CT score combined with serum sCD40L and fibulin-5 has certain predictive value for poor prognosis in sTBI patients.

Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.

Objective To detect and analyze the susceptibility genes of methyl acetate poisoning in patients by whole exome sequencing. Methods Two patients with occupational acute severe methyl acetate poisoning and their first-degree relatives who work in the same occupation and position with similar working hours were selected as the research subjects by judgment sampling method. Peripheral blood was collected for whole exome sequencing. The sequencing data was compared with the public genome database to screen the mutation sites and find out the gene sites related to methyl acetate poisoning. The suspected pathogenic mutation genes were annotated and interpreted. Results The results of whole exome sequencing showed that there were 40 differential genes between the patients with methyl acetate poisoning and their first-degree relatives, including 80 single nucleotide polymorphisms and eight Indel with specific marker sequence index. Among these, the genes with strong correlation were carboxyesterase 1 (CES1) and mucin (MUC) 5B. The CES1 gene loci c.248C>T (p.Ser83Leu) heterozygous mutations, MUC5B gene loci c.6635C>T (p.Thr2212Met) and c.7685C>T (p.Thr2562Met) heterozygous mutations in patients with methyl acetate poisoning were detected. They were missense mutations. By constructing a protein-protein interaction network, a total of 11 pairs of interactions with high levels of evidence were identified, involving genes such as lysine methyltransferase 2C, HECT and RLD domains containing E3 ubiquitin protein ligase 2, neutrophil cytoplasmic factor 1, nicotinamide adenine dinucleotide phosphate oxidase 3, C-terminal binding protein 2, zinc finger protein 717, FSHD region gene 2 family member C, FSHD region gene 1, MUC4, MUC6, MUC5B, and MUC12. Conclusion The polymorphism of CES1 and MUC5B genes may be related to the occurrence and development of methyl acetate poisoning in patients.

{L-End}Objective To investigate the effect and mechanism of low dose metformin in delaying pulmonary fibrosis in silicosis mice. {L-End}Methods The specific pathogen free C57BL/6 male mice were randomly divided into four groups,with six mice in each group. Mice in the silicosis model group and the metformin intervention group were given 20 μL of a mass concentration of 250 g/L silica suspension, and mice in the blank control group and the drug control group were given 20 μL of 0.9% sodium chloride solution, using tracheal exposure method. After 72.0 hours of dust exposure, the mice of drug control group and metformin intervention group were intraperitoneally injected with metformin at a dose of 65 mg/kg body mass, while the mice in the blank control group and the silicosis model group were given 0.9% sodium chloride solution at the same volume, once every other day for 28 days. After the treatment, histopathological change of the lungs was observed, lung organ coefficient was calculated, degree of pulmonary fibrosis was evaluated with Ashcroft score, and mRNA expression of fibronectin (Fn)1 and collagen typeⅠ(COLⅠ) alpha 1 (Col1a1) in lung tissues were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of FN and COLⅠ in lung tissues was determined by Western blot. {L-End}Results The results of histopathological examination of the lungs showed that there were no inflammation and fibrosis in the lungs of mice in the blank control group and the drug control group; mice in silicosis model group had inflammation and fibrosis in lung; the degree of lung inflammation and fibrosis was reduced in the mice of metformin intervention group compared with the silicosis model group. The lung organ coefficient, Ashcroft score, the relative expression of Fn1 and Col1a1 mRNA, the relative expression of FN and COLⅠprotein in lung tissues increased in silicosis model group (all P<0.05), compared with those in both blank control group and drug control group. The indexes above decreased of mice in the metformin intervention group than those in the silicosis model group (all P<0.05). {L-End}Conclusion Low-dose metformin can delay the progression of pulmonary fibrosis in silicosis mice. The mechanism may be related to metformin's improving excessive deposition of extracellular matrix induced by silica.

Background Lead exposure induces microglial cell death, of which the mechanism is unclear. Ferroptosis is a new death form and its role in microglia death has not been reported. Objective To investigate the role of ferroptosis in microglia following lead exposure in order to provide a theoretical basis for the mechanism of lead neurotoxicity. Methods Microglial cell line BV-2 cells were co-cultured with 0, 10, 20 and 40 μmol·L⁻¹ lead acetate for 24 h. The 40 μmol·L⁻¹ lead acetate group with iron chelator (DFO) was named the 40+DFO group. Changes in BV-2 cell morphology after lead exposure were observed under an inverted microscope; tissue iron kit and glutathione kit were used to detect intracellular iron and glutathione (GSH) respectively; flow cytometry was applied to detect lipid reactive oxygen species (lipid ROS) immunofluorescence intensity. Western blotting and qPCR were adopted to detect the expressions of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor 1 (TFR-1), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1) protein and mRNA. Results Compared with the control group, the number of BV-2 cells decreased with increasing doses of lead and the cells showed a large, round amoeboid shape. The intracellular levels of iron of BV-2 cells were (1.08±0.04), (1.29±0.03), and (1.72±0.10) mg·g⁻¹ (calculated by protein, thereafter) in the 10, 20, and 40 μmol·L⁻¹ lead acetate groups, respectively, significantly higher than that in the control group (P<0.05), and the intracellular level of iron in the 40+DFO group, (1.34±0.10) mg·g⁻¹, was lower than that in the 40 μmol·L⁻¹ lead acetate group, (1.72±0.03) mg·g⁻¹ (P<0.05). Compared with the control group, the TFR-1 and DMT1 protein and mRNA expressions were increased in BV-2 cells in the 10, 20, 40 μmol·L⁻¹ lead acetate groups (P<0.05), especially in the 40 μmol·L⁻¹ lead acetate group; the FPN1 protein expression did not change significantly, but the FPN1 mRNA expressions in BV-2 cells in the 10, 20, 40 μmol·L⁻¹ lead acetate groups were significantly decreased (P<0.05). Compared with the control group, the intracellular GSH level decreased and the lipid ROS content increased in all three lead acetate groups; compared with the 40 μmol·L⁻¹ lead acetate group, the GSH level increased by 12.30% and the lipid ROS content decreased by 13.00% in the 40+DFO group (P<0.05). The expressions of GPX4 protein were reduced to 50.00%, 35.00%, and 17.00% of that of the control group in the 10, 20, and 40 μmol·L⁻¹ lead acetate groups respectively, while the expressions of GPX4 mRNA were also significantly reduced; the expressions of SLC7A11 protein and mRNA in the 20 and 40 μmol·L⁻¹ lead acetate groups were lower than that in the control group, with the most significant decrease in the 40 μmol·L⁻¹ lead acetate group (P<0.05). Conclusion Lead exposure could induce ferroptosis in BV-2 cells, in which iron transport imbalance and oxidative damage might be involved.

Objective:To preliminarily observe the clinical efficacy of microwave hyperthermia combined with intensity-modulated radiotherapy (IMRT) and chemotherapy for patients with locally advanced gastric cancer.Methods:Forty patients who could not been operated or refused operation were enrolled in this clinical trial, who were confirmed as locally advanced proximal or distal gastric cancer by gastroscopy pathology and imaging. Radiotherapy was delivered by IMRT technology for 5 times per week with a total dose of 46 to 56 Gy (median dose of 50 Gy) in 25 to 28 fractions. Synchronous hyperthermia was given at 42 to 44℃ twice a week, 45 min/time. S-1 or capecitabine-based synchronous chemotherapy was performed, d1-14/3 weeks. The symptom remission rate, adverse reactions, objective remission rate (complete and partial remission) and survival were observed.Results:A total of 40 patients, aged between 56 and 83 years (median age of 71 years), were enrolled in this study. The male-to-female ratio was 7: 1. Among them, 38 cases (95%) showed symptom remission. The most common adverse reactions were grade 1-2 gastrointestinal reactions and leukopenia. The objective remission rate was 87.5%, the 2-year progression-free survival and overall survival rates were 68.6% and 70.5%, respectively.Conclusion:Preliminary findings demonstrate that microwave hyperthermia combined with chemoradiotherapy achieve satisfactory outcomes and yield tolerable toxicity in patients with locally advanced gastric cancer.