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 explore the impact of negative perfectionism on academic procrastination, as well as the mediating role of anxiety and the moderating role of negative cognitive emotion regulation strategies.Methods:In December 2022, a cross-sectional survey was conducted on 4 178 students from a medical college in Heilongjiang Province. The Zi negative perfectionism questionnaire, procrastination assessment scale-student, generalized anxiety disorder-7, and cognitive emotion regulation questionnaire were used to conduct the questionnaire survey, and 4 004 valid questionnaires were recovered. SPSS 26.0 statistical software was used for common method deviation test, descriptive statistics and correlation analysis, PROCESS macro program was used for mediation and moderation effect analysis.Results:(1) The scores of nursing students' negative perfectionism, anxiety, negative cognitive emotion regulation strategy, and academic procrastination were (120.48±23.40), (12.75±5.36), (44.82±11.20), and (42.95±14.30), respectively. (2) Negative perfectionism was positively correlated with anxiety ( r=0.311, P<0.01) and academic procrastination ( r=0.113, P<0.01). Academic procrastination was positively correlated with anxiety ( r=0.190, P<0.01) and negative cognitive emotion regulation strategies ( r=0.260, P<0.01). (3) Anxiety played a partially mediating role between negative perfectionism and academic procrastination, with direct effect and mediating effect accounting for 49.11% (0.055/0.112) and 50.89% (0.057/0.112) of the total effect, respectively. (4) The effect of negative perfectionism on anxiety was moderated by negative cognitive emotions, and the predictive effect of negative perfectionism on anxiety was stronger in nursing college students with high negative cognitive emotion ( β=0.231, P<0.001). Conclusion:Among nursing college students, negative perfectionism can predict academic procrastination through anxiety, and cognitive emotion regulation strategies moderate the predictive effect of negative perfectionism on anxiety.

Objective:To explore the impact of negative perfectionism on academic procrastination, as well as the mediating role of anxiety and the moderating role of negative cognitive emotion regulation strategies.Methods:In December 2022, a cross-sectional survey was conducted on 4 178 students from a medical college in Heilongjiang Province. The Zi negative perfectionism questionnaire, procrastination assessment scale-student, generalized anxiety disorder-7, and cognitive emotion regulation questionnaire were used to conduct the questionnaire survey, and 4 004 valid questionnaires were recovered. SPSS 26.0 statistical software was used for common method deviation test, descriptive statistics and correlation analysis, PROCESS macro program was used for mediation and moderation effect analysis.Results:(1) The scores of nursing students' negative perfectionism, anxiety, negative cognitive emotion regulation strategy, and academic procrastination were (120.48±23.40), (12.75±5.36), (44.82±11.20), and (42.95±14.30), respectively. (2) Negative perfectionism was positively correlated with anxiety ( r=0.311, P<0.01) and academic procrastination ( r=0.113, P<0.01). Academic procrastination was positively correlated with anxiety ( r=0.190, P<0.01) and negative cognitive emotion regulation strategies ( r=0.260, P<0.01). (3) Anxiety played a partially mediating role between negative perfectionism and academic procrastination, with direct effect and mediating effect accounting for 49.11% (0.055/0.112) and 50.89% (0.057/0.112) of the total effect, respectively. (4) The effect of negative perfectionism on anxiety was moderated by negative cognitive emotions, and the predictive effect of negative perfectionism on anxiety was stronger in nursing college students with high negative cognitive emotion ( β=0.231, P<0.001). Conclusion:Among nursing college students, negative perfectionism can predict academic procrastination through anxiety, and cognitive emotion regulation strategies moderate the predictive effect of negative perfectionism on anxiety.

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.

A 41-year-old female patient received long-term treatment with metformin, glimepiride, sitagliptin, and acarbose for type 2 diabetes mellitus. Due to elevated blood-glucose, the hypoglycemic regimen was adjusted to metformin, acarbose, and dulaglutide (1.5 mg, subcutaneously injected once a week). After each injection of dulaglutide, the patient had severe anorexia but no intervention was given because that the patient could tolerate. Empagliflozin 10 mg orally once daily were added 3 days after the first injection and then the dose was adjusted to 10 mg next day. The day after the fourth injection, the patient developed dizziness, nausea, vomiting, general fatigue, etc. Laboratory tests showed blood glucose 20 mmol/L, arterial blood pH 7.22, partial pressure of carbon dioxide 22.1 mmHg, bicarbonate concentration 8.8 mmol/L, standard bicarbonate 12 mmol/L, total carbon dioxide content 10 mmol/L, ketone body in urine (+++), and urine sugar (++++). Diabetic ketoacidosis was diagnosed. Considering that severe anorexia after the application of dulaglutide caused serious insufficient carbohydrate intake and then empagliflozin-induced diabetic ketoacidosis was stimulated, the 2 drugs were discontinued and symptomatic and supportive treatments were given. Five days later, laboratory tests showed post-lunch blood glucose 10.1 mmol/L, ketone body in urine (+), negative urine sugar, and urine pH 5.5. Empagliflozin 5 mg once daily was added and laboratory tests showed carbon dioxide binding capacity of the blood 23.2 mmol/L, urine ketones (+++), urine sugar (++++), and uric acidity 5.0 four days later. The patient insisted on leaving the hospital. After discharge, she was treated with recombinant insulin glargine, acarbose, and empagliflozin. At 1 month of follow-up, symptoms of diabetic ketoacidosis did not recur.

A 41-year-old female patient received long-term treatment with metformin, glimepiride, sitagliptin, and acarbose for type 2 diabetes mellitus. Due to elevated blood-glucose, the hypoglycemic regimen was adjusted to metformin, acarbose, and dulaglutide (1.5 mg, subcutaneously injected once a week). After each injection of dulaglutide, the patient had severe anorexia but no intervention was given because that the patient could tolerate. Empagliflozin 10 mg orally once daily were added 3 days after the first injection and then the dose was adjusted to 10 mg next day. The day after the fourth injection, the patient developed dizziness, nausea, vomiting, general fatigue, etc. Laboratory tests showed blood glucose 20 mmol/L, arterial blood pH 7.22, partial pressure of carbon dioxide 22.1 mmHg, bicarbonate concentration 8.8 mmol/L, standard bicarbonate 12 mmol/L, total carbon dioxide content 10 mmol/L, ketone body in urine (+++), and urine sugar (++++). Diabetic ketoacidosis was diagnosed. Considering that severe anorexia after the application of dulaglutide caused serious insufficient carbohydrate intake and then empagliflozin-induced diabetic ketoacidosis was stimulated, the 2 drugs were discontinued and symptomatic and supportive treatments were given. Five days later, laboratory tests showed post-lunch blood glucose 10.1 mmol/L, ketone body in urine (+), negative urine sugar, and urine pH 5.5. Empagliflozin 5 mg once daily was added and laboratory tests showed carbon dioxide binding capacity of the blood 23.2 mmol/L, urine ketones (+++), urine sugar (++++), and uric acidity 5.0 four days later. The patient insisted on leaving the hospital. After discharge, she was treated with recombinant insulin glargine, acarbose, and empagliflozin. At 1 month of follow-up, symptoms of diabetic ketoacidosis did not recur.

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.