This study was designed to investigate the correlation between autophagy and polarization of macrophages in atherosclerosis (AS) plaque in arteriosclerosis obliterans amputees. Femoral artery specimens from arteriosclerosis obliterans amputees were performed hematoxylin and eosin (HE) staining, oil red O and immunofluorescence staining to observe the morphology of atherosclerotic plaque, phenotype of macrophages and autophagy in plaque; using real-time quantitative RT-PCR technology to detect the mRNA level of M1 and M2 type markers in arterial tissue; to analyze polarized signal pathway and autophagy protein levels in macrophages by Western blotting. Arterial specimens staining showed obvious lipid deposition and obvious infiltration of amount of foam cells and inflammatory cells. Macrophages were mainly expression M1 type in percentage in fibrous plaque. Although both M1 and M2 macrophages were upregulated in atheromatous plaque, the increase was dominant in M2 type in percentage. The level of autophagy was significantly higher in the atheromatous plaque than that of fibrous plaque. The expression of tumor necrosis factor- α (TNF-α), monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and interleukin-12 (IL-12) mRNA was significantly higher in fibrous plaque than that of atheromatous plaque (P < 0.01 or 0.05), and arginase-1 (Arg-1), transforming growth factor-β (TGF-β), CD163 and interleukin-10 (IL-10) mRNA was significantly lower than that in atheromatous plaque (P < 0.01). The levels of p-STAT1 and NF-κB were significantly increased in fibrous plaque (P < 0.01), while p-STAT6 expression was significantly increased in atheromatous plaque (P < 0.01). The level of LC3-II was significantly higher in atheromatous plaque than that in fibrous plaque (P < 0.01). Macrophages in early atherosclerotic plaque were induced to M1 type through p-STAT1/NF-κB pathway and expressed moderate levels of autophagy; while macrophages in advanced plaques were induced to polarization of M2 type through p-STAT6 pathway. M2 macrophages expressed a higher level of autophagy than M1 macrophages.

Objective: To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor (EGFR), phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2) and activated protein-1 (AP-1), the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa.
Methods: Thirty Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), or Pishu (BL 20) and Weishu (BL 21), once a day, for a total of 8 d. Histological changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERK1/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-1 were measured by Western blots.
Results: Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group (P<0.01,P<0.05,P<0.05). Compared with rats in the model group, gastric mucosal damage was milder, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the moxibustion group (allP<0.01).
Conclusion:Moxibustion at Zusanli (ST 36), Zhongwan (CV 12), Pishu (BL 20) and Weishu (BL 21) couldincrease EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and promote restoration of gastric mucosal damage.

Background Polycyclic aromatic hydrocarbons (PAHs) are widely known atmospheric pollutants, which can cause serious harm to human body and ecological environment. Objective To analyze the concentrations and sources of PAHs in atmospheric PM_2.5 in Zhifu District and Longkou City during the heating period in Yantai. Methods Two monitoring sites in Zhifu District and Longkou City of Yantai were selected, and PM_2.5 sample collection was carried out from April 2023 to March 2024. Gas chromatography-mass spectrometry was applied to analyze the concentrations of PAHs in atmospheric PM_2.5 during the heating period (from November 2023 to March 2024) and the non-heating period (from April to October 2023). The concentrations of PAHs in the two periods were compared and the sources of PAHs during the heating period were analyzed by characteristic ratio method. Results During the heating period, the total concentration ranges of PAHs in atmospheric PM_2.5 at the monitoring sites in Zhifu District and Longkou City of Yantai were (1.59-23.70) ng·m⁻³ and (2.08-149.72) ng·m⁻³ respectively, and the medians (M) and the 25th and 75th percentiles (P₂₅, P₇₅) were 4.99 (2.61, 8.09) ng·m⁻³ and 15.46 (8.15, 29.05) ng·m⁻³ respectively. The PAHs concentrations in Longkou City were significantly higher than those in Zhifu District in all months (P<0.05). The highest median total concentrations of PAHs in both sites were reported in January (8.14 ng·m⁻³ and 81.56 ng·m⁻³ respectively). In the non-heating period, the M (P₂₅, P₇₅) of the total PAHs concentrations at the two sites were 1.59 (1.59, 2.78) ng·m⁻³ and 4.11 (2.94, 7.97) ng·m⁻³ respectively, much lower than those in the heating period (P<0.01). The order of composition of PAHs by ring number in PM_2.5 at both sites was 4-ring> 5-ring> 6-ring, with the 4-ring contributing the largest proportion (65.33% and 46.39% respectively). Fluoranthene had the highest concentration among PAHs at both sites, with concentrations M (P₂₅, P₇₅) of 1.29 (0.51, 1.78) ng·m⁻³ and 2.32 (1.30, 3.82) ng·m⁻³ respectively. The characteristic ratios of fluoranthene/(fluoranthene + pyrene), fluoranthene/pyrene, benzo[a]anthracene/(benzo[a]anthracene + chrysene), pyrene/benzo[a]pyrene, benzo[a]pyrene/(benzo[a]pyrene + chrysene), benzo[a]pyrene/benzo[g,h,i]pyrene, and indeno[1,2,3-c,d]pyrene/(indeno[1,2,3-c,d]pyrene + benzo[g,h,i]pyrene) in Zhifu District were 0.62, 1.65, 0.41, 4.48, 0.50, 0.93 and 0.47 respectively, and those in Longkou were 0.57, 1.35, 0.40, 2.89, 0.29, 0.79 and 0.47 respectively. The results showed that PAHs pollutants were generated by combination of coal combustion, vehicle exhaust emissions and gasoline combustion. Conclusion During the heating period in Yantai area, the total concentration of PAHs in atmospheric PM_2.5 is significantly higher than that in the non-heating period. Among them, during the heating period, the pollution level in Longkou City is significantly higher than that in Zhifu District. The local PAHs may be sourced from mixed pollution, and the main sources include gasoline, and coal combustion and vehicle exhaust emissions.

BACKGROUND: Programmed cell death 1 or programmed cell death ligand 1 inhibitor (PD-1/PD-L1 inhibitor) and docetaxel, as the standard second-line treatments of advanced non-small cell lung cancer (NSCLC) patients, have limited effects. There are few studies on whether docetaxel combined with PD-1/PD-L1 inhibitor can increase the efficacy and make patients better benefit. The aim of this study is to evaluate the efficacy and safety of docetaxel combined with PD-1/PD-L1 inhibitor for the second-line treatment of stage IV NSCLC patients. METHODS: Stage IV NSCLC patients (n=118) who received treatment at Shandong Cancer Hospital between October 1, 2018, and December 31, 2020, were retrospectively analyzed. They were divided into observation group (n=69) and control group (n=49) according to different treatment plan. Observation group was given docetaxel plus PD-1/PD-L1 inhibitor, while control group was given PD-1/PD-L1 inhibitor. The clinical curative effect and the incidence of adverse reactions of grade 3 and above were compared between the two groups. RESULTS: The disease control rate (DCR) was higher in the observation group (89.9%) than that in the control group (73.5%) (P=0.019), and the objective response rate (ORR) showed no significant difference between observation group (24.6%) and control group (16.3%) (P=0.276). Till June 22, 2021, the 1-year PFS rate showed no difference between observation group (16.5%) and control group (7.7%) (P=0.205). During the treatment period, the adverse reactions of the two groups were mostly grade 1 to 2, and could be tolerated. The incidence of bone marrow suppression in observation group was higher than that in the control group (P<0.05), and the remaining adverse reactions were not statistically different from control group. Cox regression analysis showed that performance status (PS) (P=0.020) and age (P=0.049) were independent prognostic factors for the effect of docetaxel combined with PD-1/PD-L1 inhibitor. CONCLUSIONS The second-line treatment with docetaxel plus PD-1/PD-L1 inhibitor in patients with stage IV NSCLC can improve the DCR and prolong the PFS, and the adverse reactions are tolerable.