Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Objective To establish a DNA quantitation method based on dithiothreitol(DTT)-crystal vio-let.Methods DTT was used to decolorize crystal violet,mixed with different concentrations of λ-DNA and salmon sperm DNA standard samples or concentration standard samples,and the absorbance was read at 595 nm wavelength by microplate reader,and compared with the results of ultraviolet absorbance method.DTT-crystal violet method and ultraviolet absorbance method were used to compare the concentration of plasmid samples and the concentration of genomic DNA samples of cervical exfoliated cells.The protein tolerance of the two methods was assessed by simulating protein contaminants with bovine serum albumin(BSA).Results In the quantification of λ-DNA and salmon sperm DNA,the DTT-crystal violet method had a robust linear correlation between the absorbance at 595 nm and DNA concentration(r2＞0.95),and the measured concentrations of the standard samples were not significantly different from the theoretical concentrations of the prepared standard samples(P＞0.05).There was no significant difference in the concentration of plasmid samples measured by DTT-crystal violet method and ultraviolet absorption method(P＞0.05).The concen-tration of DNA samples from cervical exfoliated cells measured by ultraviolet absorption method was positive-ly correlated with that by DTT-crystal violet method(r=0.94,P＜0.01).The concentration of the standard sample containing BSA 1 μg/μL measured by ultraviolet absorption method was higher than that of the con-trol sample,and the difference was statistically significant(P＜0.01),whereas the DTT-crystal violet method was not significantly affected(P＞0.05).Conclusion DTT-crystal violet method has obvious advantages over the existing DNA quantitation method,and is suitable for DNA quantitative analysis in scientific research and clinic.

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Objective To explore the effect of adeno-associated virus sense transfection up-regulating the expression level of the growth and differential factor 11 (GDF11) in vivo on aortic injury in type 2 diabetic mellitus rats (T2DM).Methods Nine-week-old male SD rats were randomly selected to establish a T2DM model by using high-sugar and high-fat chow plus small-dose streptozotocin (STZ) combined induction.Both normal rats and dia-betic model rats were randomly divided into five groups:blank control group (Control group) , negative virus con-trol group (NC group), GDF11 adeno-associated virus group (GDF11 group), diabetic group (DM group), and diabetic + GDF11 adeno-associated virus group (DM+GDF11 group) .After 8 weeks of feeding, the serum con-centrations of insulin (INS) , advanced glycosylation end products (AGES) , recombinant growth transforming fac-tor 11 (GDF11), total cholesterol (T-CHO), triglycerides (TG), low-density lipoproteins (LDL-C), high-densi-ty lipoproteins (HDL-C) , asymmetric dimethylarginine (ADMA) , and malondialdehyde (MDA) were assayed in the rats;periodic acid-schiff stain(PAS stain) was used to observe the sites of glycogen deposition, and hematoxy-lin-eosin staining (HE) was used to observe vascular damage.Scanning electron microscopy was used to observe the damage of vascular endothelial cells and vascular elastic fibers, and protein blotting and immunohistochemistry were used to detect the expression levels of vascular injury-related proteins.Protein blotting and immunohistochem-istry were used to detect the expression levels of vascular injury-related proteins.Results The biochemical inde-xes showed that the serum concentrations of AGES, T-CHO, TG, LDL-C and MDA were higher in the DM group than those in the Control group (P<0.05), the concentrations of INS, GDF11, HDL-C and ADMA were signifi-cantly lower than those in the Control group (P<0.05) , and the concentrations of AGES and HDL-C were not sig-nificantly lower in the DM+GDF11 group compared with the DM group (P<0.05) .HDL-C was not significantly different from the DM group, and several other data were improved (P<0.05) .Pathological staining suggested that PAS staining in the DM group suggested that glycogen particles deposited in the endothelium and subendotheli-um of the aorta, HE staining observed thickening of the aortic mesentery, endothelial cells and elastic fibers broke off in an irregular alignment, and electron microscopy observed endothelial damage in the vasculature and elastic fi-bers broke off in the DM group, and these changes attenuated in the DM+GDF11 group.Protein blotting and im-munohistochemistry indicated that the expression of endothelial cell-associated proteins decreased in the DM group (P<0.05) , and mesenchymal markers elevated in the DM group (P<0.05) , these proteins were regressed in the DM+GDF11 group, and the difference was statistically significant (P <0.05).Conclusion Increasing the expression level of GDF11 in vivo can improve aortic vascular injury caused by diabetes mellitus, which is inferred that it may be related to the inhibition of endothelial mesenchymal transition to protect the function of vascular endo-thelial cells and thus improve vascular injury.

Objective:To examine the relationship between fasting blood glucose(FBG)levels and H. pylori infection, as well as their impact on eradication and recurrence rates.Methods:A total of 1 584 patients with type 2 diabetes, ranging in age from 44 to 91 years old(mean age of 66.6±7.6 years), were included in this study conducted at the Physical Examination Center of the First Hospital of Lanzhou University between March 2010 and December 2019.Of the total participants, 1 063(67.1%)were male and 521(32.9%)were female.Logistic regression analysis was performed to investigate the impact of age, gender, fasting blood glucose, and H. pylori infection on the patients.In the study, 263 patients in the euglycemic control group(HbA1c<7%), 271 patients in the poor glycemic control group(HbA1c≥7%), and 269 patients in the control group underwent H. pylori eradication using bismuth-containing quadruple therapy, and the eradication efficacy, adverse reactions, and recurrence rates were compared after 1 year.Results:In patients with type 2 diabetes, the infection rate of H. pylori was found to be 48.2%.Further regression analysis revealed that poor glycemic control increased the risk of H. pylori infection( OR=1.611, 95% CI: 1.269~2.045, P<0.01). However, the constituent ratio and infection rate of different hypoglycemic drug groups did not show any significant statistical difference.The eradication rate of H. pylori was 90.9%, and there was no significant difference in the eradication rate among different blood glucose groups and control groups.However, after 1 year, the recurrence rate was 3.8%, with a higher rate observed in the poor glycemic control group compared to the euglycemic control group and the control group( P<0.05). There was a statistically significant difference in constipation as the main side effect of eradication therapy between the diabetic group and the control group[25.1%(134/253) vs.16.4%(44/269), P<0.01]. Conclusions:Diabetic patients with fasting hyperglycemia or poor glycemic control are at an increased risk of H. pylori infection.Additionally, these patients have a higher risk of recurrence after eradication.Therefore, it is important for clinicians to closely monitor and manage glycemic control in diabetic patients to reduce the risk of H. pylori infection and improve treatment outcomes.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To select the relevant evidence of percutaneous pericardial drainage tube nursing and summarize the best evidence.Methods:Evidence-based questions were established based on PIPOST model. BMJ Best Clinical Practice, China Biology Medicine disc (CBM) , UpTodate, Cochrane Library, Joanna Briggs Institute Evidence-based Health Care Database, China Guide Network, British Guide Network, National Guide Line Clearing House (NGC) , PubMed, EMbase, Evidence-based Medicine (EBM) , Registered Nurses' Association of Ontario (RNAO) , The European Society of Cardiology (ESC) , American Heart Association (AHA) , Chinese Journal Full-text Database and Wanfang Database were conducted computer retrieval. The search time was from the establishment of the database to December 31, 2020. Two researchers respectively evaluated the quality of the included literature and extracted data and summarized and summarized the evidence that met the standards.Results:Finally, 12 articles were included, including 1 evidence summary, 2 systematic reviews, 1 systematic assesment, 2 guidelines, 1 expert consensus and 5 case series studies. Finally, 11 pieces of evidence were formed, including 6 themes such as drainage tube selection, puncture wound nursing, drainage flow control, flushing and sealing of the tube, observation and recording points, extubation indications and care.Conclusions:This study summarizes the best evidence for percutaneous pericardial drainage tube nursing, which provides evidence-based basis for improving the quality of percutaneous pericardial drainage tube care.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.