Background Silicosis is a fatal form of pulmonary fibrosis caused by the inhalation of silica dust. Although the underlying pathogenesis remains unclear, and the macrophage-mediated immune response plays a central role in its development. Objective To investigate the expression, functional role, and upstream regulatory mechanism of C-C motif chemokine ligand 22 (CCL22) in silica-induced pulmonary fibrosis. Methods Through bioinformatics analysis, we identified CCL22 as a potential key factor in pulmonary fibrosis. We established in vitro models by stimulating human monocytic leukemia cells (THP-1) and peripheral blood mononuclear cell-derived macrophages (PBMC-m) with crystalline silica (CS). The regulation of CCL22 expression by CS was validated using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Subsequently, a conditioned co-culture system comprising macrophages and lung epithelial cells (BEAS-2B) was developed to evaluate the effects of CCL22 on lung epithelial cell function. Furthermore, the molecular mechanisms underlying CS-induced CCL22 secretion by macrophages were investigated using bioinformatics analysis, Western blot, specific inhibitors, qRT-PCR, and ELISA. Results Bioinformatics analysis identified CCL22 as a key upregulated molecule in pulmonary fibrosis. In vitro experiments confirmed that CS treatment significantly enhanced CCL22 mRNA transcription and protein secretion in THP-1 and PBMC-m cells (P<0. 0001). In the co-culture system, supernatant from CS-stimulated macrophages with stable CCL22 knockdown significantly inhibited the scratch-healing ability and fibrotic process of BEAS-2B cells, and reversed the epithelial-mesenchymal transition (EMT) phenotype compared to the control group. Mechanism studies found that, compared to other transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB), the inhibition of of specific protein 1 (SP1) most significantly attenuated the CS-induced upregulation of CCL22. Furthermore, pathway inhibition experiments demonstrated that inhibiting extracellular signal-regulated kinase (ERK) reduced both CCL22 expression and p-SP1. Conversely, SP1 intervention did not affect ERK activation. Conclusion CS promotes CCL22 secretion by macrophages through the Raf/ERK-Sp1 signaling pathway, thereby driving fibrotic changes in pulmonary epithelial cells.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Objective To investigate the relationship between between the levels of serum malondialdehyde(MDA)and superoxide dismutase(SOD),the balance of oxidative/antioxidant stress,and the prognostic nu-tritional index(PNI)and the risk of early neurological deterioration in patients with acute ischemic stroke(AIS).Methods A total of 95 patients with suspected AIS admitted to the Second People's Hospital of Fos-han,Foshan from January to April 2023 were selected as the research subjects.Among them,71 patients who were finally diagnosed with AIS were included in the stroke group,and the remaining 24 non-AIS patients were included in the control group.According to the National Institutes of Health Stroke Rating Scale(NIH-SS)score,the stroke group was divided into the moderate-severe stroke group and the mild stroke group.Ac-cording to whether early neurological deterioration(END)occurred,it was divided into the END group and the non-END group.To analyze the correlations between the levels of serum SOD and MDA,SOD/MDA,and the PNI and the severity of stroke.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of each index for the risk of END.By fitting the indicators with high diagnostic efficacy,a Fisher discriminant function model for evaluating the risk of END was established to verify the overall accura-cy rate.Results The levels of serum MDA and SOD,SOD/MDA and the PNI in the moderate to severe stroke group were statistically different from those in the mild stroke group(P＜0.05).There were statistically sig-nificant differences in the levels of serum MDA and SOD,SOD/MDA and the PNI among the END group,the non-END group and the control group(P＜0.05).The areas under the curve(AUC)of SOD,MDA,SOD/MDA and PNI for evaluating END were 0.692,0.727,0.777 and 0.819,respectively.The Fisher discriminant function model established by fitting the NIHSS score,the SOD/MDA and the PNI has an overall accuracy rate of 85.9％.Conclusion The END risk prediction model established by applying the Fisher discriminant function can provide early and objective reference basis for clinical prediction of END risk and has certain practical value.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Objective:To investigate the current status of occupational stress among electronic manufacturing workers in Qingdao and analyze its effect on depressive symptoms and anxiety symptoms.Methods:From July to September 2022, a cluster random sampling method was employed to select frontline workers from 14 electronic manufacturing enterprises in Qingdao as the study subjects. A total of 1134 questionnaires were distributed, with 1000 valid questionnaires collected, yielding an effective response rate of 88.18%. The Core Occupational Stress Scale (COSS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were adopted to assess occupational stress, depressive symptoms, and anxiety symptoms, respectively. Binary logistic regression was employed to analyze influencing factors of occupational stress and its effects on depressive and anxiety symptoms.Results:The detection rates of occupational stress, depressive symptoms, and anxiety symptoms were 15.1% (15/1000), 7.9% (79/1000), and 13.8% (138/1000), respectively. The influencing factor analysis of occupational stress revealed that female gender ( OR=0.621, 95% CI: 0.434-0.890) and weekly working hours of 45-48 hours ( OR=0.537, 95% CI: 0.309-0.935) were protective factors ( P<0.05), while weekly working hours ≥55 hours ( OR=2.176, 95% CI: 1.290-3.670) and shift work ( OR=2.038, 95% CI: 1.412-2.940) were risk factors ( P<0.05). Spearman correlation analysis showed that the COSS score was positively related with the PHQ-9 score and the GAD-7 score ( rs=0.438, 0.289, P<0.01). Workers judged with occupational stress had 3.596 times (95% CI: 2.181-5.931, P<0.001) and 3.121 times (95% CI: 2.046-4.761, P<0.001) higher risks of detecting depressive and anxiety symptoms compared to those without occupational stress. Conclusion:Electronic manufacturing workers in Qingdao experience a certain level of occupational stress, which may increase the risk of developing depressive and anxiety symptoms. Enterprises should implement appropriate interventions to promote workers' mental health.

Objective To examine the effects of SMAD4 on the proliferation and apoptosis of ovarian granulosa cells in rats with poly-cystic ovary syndrome(PCOS).Methods A PCOS rat model was established using DHEA,and ovarian granulosa cells were extracted and cultured in vitro.The expression of SMAD4 in ovarian granulosa cells was detected by quantitative real-time PCR and Western blot-ting.SMAD4-siRNA was transfected into ovarian granulosa cells from PCOS rats.The expression of SMAD4 mRNA after transfection was determined by quantitative real-time PCR.Western blotting was performed to detect the expression levels of PCNA,BAX,and BCL-2 proteins after transfection.A CCK-8 assay was performed to evaluate cell growth after siRNA interference.Results The HE staining results revealed that the number of ovarian follicular vacuoles increased and that the number of granulosa cell layers and corpus luteum decreased,thus indicating the establishment of a PCOS model.The FSHR positivity rate exceeded 95％.SMAD4 expression in ovarian granulosa cells was higher in the PCOS group than in the control group(P＜0.05).Furthermore,siRNA effectively reduced SMAD4 expression in ovarian granulosa cells of PCOS rats(P＜0.01),promoted proliferation,and inhibited the apoptosis of granulosa cells.Con-clusion The hindered growth of ovarian granulosa cells in PCOS rats may be linked to the overexpression of SMAD4 mRNA,which sug-gests that targeting SMAD4 could be a promising approach for treating ovulatory abnormalities in patients with PCOS.

Objective:To investigate the current status of occupational stress among electronic manufacturing workers in Qingdao and analyze its effect on depressive symptoms and anxiety symptoms.Methods:From July to September 2022, a cluster random sampling method was employed to select frontline workers from 14 electronic manufacturing enterprises in Qingdao as the study subjects. A total of 1134 questionnaires were distributed, with 1000 valid questionnaires collected, yielding an effective response rate of 88.18%. The Core Occupational Stress Scale (COSS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were adopted to assess occupational stress, depressive symptoms, and anxiety symptoms, respectively. Binary logistic regression was employed to analyze influencing factors of occupational stress and its effects on depressive and anxiety symptoms.Results:The detection rates of occupational stress, depressive symptoms, and anxiety symptoms were 15.1% (15/1000), 7.9% (79/1000), and 13.8% (138/1000), respectively. The influencing factor analysis of occupational stress revealed that female gender ( OR=0.621, 95% CI: 0.434-0.890) and weekly working hours of 45-48 hours ( OR=0.537, 95% CI: 0.309-0.935) were protective factors ( P<0.05), while weekly working hours ≥55 hours ( OR=2.176, 95% CI: 1.290-3.670) and shift work ( OR=2.038, 95% CI: 1.412-2.940) were risk factors ( P<0.05). Spearman correlation analysis showed that the COSS score was positively related with the PHQ-9 score and the GAD-7 score ( rs=0.438, 0.289, P<0.01). Workers judged with occupational stress had 3.596 times (95% CI: 2.181-5.931, P<0.001) and 3.121 times (95% CI: 2.046-4.761, P<0.001) higher risks of detecting depressive and anxiety symptoms compared to those without occupational stress. Conclusion:Electronic manufacturing workers in Qingdao experience a certain level of occupational stress, which may increase the risk of developing depressive and anxiety symptoms. Enterprises should implement appropriate interventions to promote workers' mental health.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Objective To examine the effects of SMAD4 on the proliferation and apoptosis of ovarian granulosa cells in rats with poly-cystic ovary syndrome(PCOS).Methods A PCOS rat model was established using DHEA,and ovarian granulosa cells were extracted and cultured in vitro.The expression of SMAD4 in ovarian granulosa cells was detected by quantitative real-time PCR and Western blot-ting.SMAD4-siRNA was transfected into ovarian granulosa cells from PCOS rats.The expression of SMAD4 mRNA after transfection was determined by quantitative real-time PCR.Western blotting was performed to detect the expression levels of PCNA,BAX,and BCL-2 proteins after transfection.A CCK-8 assay was performed to evaluate cell growth after siRNA interference.Results The HE staining results revealed that the number of ovarian follicular vacuoles increased and that the number of granulosa cell layers and corpus luteum decreased,thus indicating the establishment of a PCOS model.The FSHR positivity rate exceeded 95％.SMAD4 expression in ovarian granulosa cells was higher in the PCOS group than in the control group(P＜0.05).Furthermore,siRNA effectively reduced SMAD4 expression in ovarian granulosa cells of PCOS rats(P＜0.01),promoted proliferation,and inhibited the apoptosis of granulosa cells.Con-clusion The hindered growth of ovarian granulosa cells in PCOS rats may be linked to the overexpression of SMAD4 mRNA,which sug-gests that targeting SMAD4 could be a promising approach for treating ovulatory abnormalities in patients with PCOS.