Objective To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.Methods Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100 μL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections.On the 15th day after irradiation,histopathological changes of the lungs of the mice were examined using HE staining,the levels of TNF-α,TGF-β,IL-1α and IL-6 in the lung tissue and serum were detected using ELISA,and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry.High-throughput sequencing of exosome miRNA was carried out to explore the changes in the signaling pathways.The mRNA expression levels of the immune-related genes were detected by qRT-PCR,and the protein expressions of talin-1,tensin2,FAK,vinculin,α-actinin and paxillin in the focal adhesion signaling pathway were detected with Western blotting.Results In the mouse models of radiation pneumonitis,injections of normal mouse serum significantly decreased the lung organ coefficient,lowered the levels of TNF-α,TGF-β,IL-1α and IL-6 in the serum and lung tissues,and ameliorated infiltration of CD45+,CD4+and Treg lymphocytes in the lung tissue(all P<0.05).The expression levels of Egfr and Pik3cd genes at both the mRNA and protein levels and the protein expressions of talin-1,tensin2,FAK,vinculin,α-actinin and paxillin were all significantly down-regulated in the mouse models after normal mouse serum treatment.Conclusion Normal mouse serum ameliorates radiation pneumonitis in mice by inhibiting the expressions of key proteins in the Focal adhesion signaling pathway.

Objective To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.Methods Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100 μL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections.On the 15th day after irradiation,histopathological changes of the lungs of the mice were examined using HE staining,the levels of TNF-α,TGF-β,IL-1α and IL-6 in the lung tissue and serum were detected using ELISA,and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry.High-throughput sequencing of exosome miRNA was carried out to explore the changes in the signaling pathways.The mRNA expression levels of the immune-related genes were detected by qRT-PCR,and the protein expressions of talin-1,tensin2,FAK,vinculin,α-actinin and paxillin in the focal adhesion signaling pathway were detected with Western blotting.Results In the mouse models of radiation pneumonitis,injections of normal mouse serum significantly decreased the lung organ coefficient,lowered the levels of TNF-α,TGF-β,IL-1α and IL-6 in the serum and lung tissues,and ameliorated infiltration of CD45+,CD4+and Treg lymphocytes in the lung tissue(all P<0.05).The expression levels of Egfr and Pik3cd genes at both the mRNA and protein levels and the protein expressions of talin-1,tensin2,FAK,vinculin,α-actinin and paxillin were all significantly down-regulated in the mouse models after normal mouse serum treatment.Conclusion Normal mouse serum ameliorates radiation pneumonitis in mice by inhibiting the expressions of key proteins in the Focal adhesion signaling pathway.

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective:To study the effect of fasting on 137Cs γ-ray radiation-induced intestinal injury in mice, and to explore the effect of fasting on fecal metabolites of mice through non-targeted metabolomics. Methods:C57BL/6 mice were divided into healthy control group, 9 Gy γ-ray whole body irradiation (WBI)/ 15 Gy γ-ray whole abdominal irradiation (WAI) group, fasting (24 h, 48 h, 72 h)+ 9 Gy WBI/ 15 Gy WAI group. After irradiation, the survival rate, spleen index and thymus index were calculated. C57BL/6 mice in non-target metabolism experiment were randomly divided into four groups: control group, fasting 24 h group, 15 Gy γ-ray WAI group, fasting 24 h + 15 Gy γ-ray WAI group, 6 mice in each group. After 15 Gy WAI, the feces of mice in each group were collected at 3.5 days for non-targeted metabolomics detection.Results:The median survival time of mice with 48 h and 24 h fasting before 9 Gy γ-ray irradiation was increased by 1 day and 4 days, and the survival rates of mice treated with 48 h and 24 h fasting before 15 Gy WAI were 16.67% and 25%, respectively. 15 Gy γ-ray WAI on mice with fasting for 24 h before irradiation could increase the body weight ( t=2.338, P=0.042) and spleen index ( t=2.289, P=0.045) at 3.5 days after irradiation. Through non-targeted metabonomic analysis, it was found that there were 30 differentially expressed metabolites in fecal samples of fasting and non-fasting mice subjected to WAI, and metabolic pathway enrichment analysis showed that there was an imbalance in the metabolic pathway of steroid biosynthesis. Conclusions:Fasting before irradiation can improve the survival rate of mice with intestinal radiation injury and change their intestinal metabolites, suggesting that pre-irradiation fasting or short-term dietary nutrition changes are involved in the regulation of intestinal radiation damage.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

Objective:To explore the moderating effect of sense of coherence in the relationship between occupational stress and depression.Methods:From June to September in 2018, migrant workers were purposively selected from the urban (including office buildings, shopping malls, barber shops or restaurants and other service enterprises) and suburban (including microelectronics, internet, clothing processing and art design and other factories) areas of Shanghai. A total of 3 034 people were investigated and 2 573 valid questionnaires were collected. Patient health questionnaire (PHQ), sense of coherence questionnaire (SOC) and job content questionnaire (JCQ) were used to investigate the levels depression, sense of coherence and occupational stress. Hierarchical regression analysis was used to analyze the moderating effect of sense of coherence on occupational stress and depression, and SPSS PROCESS macro program and Bootstrap method were used to further explore the moderating effect of sense of coherence.Results:The age of total 2 573 migrant workers was (28.24±7.33) years old and 49.79% of them were males. The scores of depression, occupational stress and sense of coherence were 6.67±4.74, 28.45±4.38 and 62.02±10.89, respectively. The depression level was positively correlated with occupational stress ( r=0.33, P=0.007), and negatively correlated with sense of coherence ( r=-0.53, P=0.003). The hierarchy regression analysis suggested that the interaction between occupational stress and sense of coherence was associated with depression symptom (β=-0.07, P=0.001). Bootstrap analysis showed that occupational stress was not associated with depression symptom with high level of sense of sense of coherence (β=0.04, 95% CI=-0.01-0.10), while occupational stress was associated with depression symptom with low level of sense of sense of coherence (β=0.19, 95% CI=0.14-0.23). Conclusion:The high level of sense of coherence has a moderating effect on the relationship between occupational stress and depressive symptoms, while the low level of sense of coherence does not have this effect.

Objective:To explore the moderating effect of sense of coherence in the relationship between occupational stress and depression.Methods:From June to September in 2018, migrant workers were purposively selected from the urban (including office buildings, shopping malls, barber shops or restaurants and other service enterprises) and suburban (including microelectronics, internet, clothing processing and art design and other factories) areas of Shanghai. A total of 3 034 people were investigated and 2 573 valid questionnaires were collected. Patient health questionnaire (PHQ), sense of coherence questionnaire (SOC) and job content questionnaire (JCQ) were used to investigate the levels depression, sense of coherence and occupational stress. Hierarchical regression analysis was used to analyze the moderating effect of sense of coherence on occupational stress and depression, and SPSS PROCESS macro program and Bootstrap method were used to further explore the moderating effect of sense of coherence.Results:The age of total 2 573 migrant workers was (28.24±7.33) years old and 49.79% of them were males. The scores of depression, occupational stress and sense of coherence were 6.67±4.74, 28.45±4.38 and 62.02±10.89, respectively. The depression level was positively correlated with occupational stress ( r=0.33, P=0.007), and negatively correlated with sense of coherence ( r=-0.53, P=0.003). The hierarchy regression analysis suggested that the interaction between occupational stress and sense of coherence was associated with depression symptom (β=-0.07, P=0.001). Bootstrap analysis showed that occupational stress was not associated with depression symptom with high level of sense of sense of coherence (β=0.04, 95% CI=-0.01-0.10), while occupational stress was associated with depression symptom with low level of sense of sense of coherence (β=0.19, 95% CI=0.14-0.23). Conclusion:The high level of sense of coherence has a moderating effect on the relationship between occupational stress and depressive symptoms, while the low level of sense of coherence does not have this effect.

Objective: To explore the effects of FOXO4 D-retro-inverso peptide (FOXO4-DRI) on the radiosensitivity of non-small cell lung cancer (NSCLC) cells. Methods: To detect the effect of FOXO4-DRI on NSCLC cells, H460 and A549 human lung cancer cells were divided into four groups, including untreated control, FOXO4-DRI, γ-ray irradiation and FOXO4-DRI + γ-ray groups. A sigle dose rate of 0.99 Gy γ-rays was used for radiation. H460 cells were administered with 6 μmol/L FOXO4-DRI and A549 cells were adiminstered with 30 μmol/L FOXO4-DRI at 10 min before radiation. Cell viability and survival were detected by CCK-8 assay and colony formation assay, respectively. Cell migration was detected by wound healing assay. Apoptosis and cell cycle arrest were detected with flow cytometry. Results: FOXO4-DRI inhibited growth of H460 and A549 cells (t=1.06-50.75, P<0.05), and decreased cell mobility (t=33.37-139.10, P<0.05) and colony formation (t=5.20-93.48, P<0.05). FOXO4-DRI also increased apoptosis (t=2.95-42.00, P<0.05) and caused a cell cycle arrest at G₀/G₁ phase accompanied with a decreased proportion of G₂/M phase (t=3.50-31.59, P<0.05). Furthermore, FOXO4-DRI increased radiosensitivity of both H460 cells and A549 cells (t=2.94-23.40, P<0.05), caused a Further Decrease of radiation-mediated mobility (t=5.25, 7.56, P<0.05) and colony formation (t=8.43-34.00, P<0.05) and a more increase of radiation-induced apoptosis (t=9.20-11.52, P<0.05). FOXO4-DRI also further decreased the proportion of G₂/M phase cells but increased the proportion of S phase cells (t=3.85-17.62, P<0.05). Conclusion FOXO4-DRI increases radiosensitivity of NSCLC cells by inducing apoptosis and suppressing cell proliferation.