Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Objective:To discuss the effect of long non-coding RNA(lncRNA)DUXAP8 in exosomes(Exo)derived from the lung cancer A549 cells on the growth and immune escape of the lung cancer cells,and to clarify the mechanism.Methods:The human lung cancer cell line A549 was cultured,and its exosomes were extracted and identified.The A549 cells were treated with PKH67-labeled Exo to observe the uptake of Exo by A549 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of lncRNA DUXAP8 in A549 cells before and after Exo treatment.The A549 cells were divided into control group(no treatment),Exo group(A549 cells treated with Exo),Exo+sh-NC group(A549 cells treated with Exo and then transfected with sh-NC),and Exo+sh-DUXAP8 group(A549 cells treated with Exo and then transfected with sh-DUXAP8).RT-qPCR method was used to detect the expression level of lncRNA DUXAP8 in A549 cells in various groups;colony formation assay was used to detect the colony formation abilities of the A549 cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)staining method was used to detect the proliferation abilities of the A549 cells in various groups.After co-culturing A549 cells in various groups with human peripheral blood lymphocytes,flow cytometry was used to detect the percentages of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in various groups;3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)method was used to detect the killing rates of human peripheral blood lymphocytes on the A549 cells in various groups.Results:The diameter of Exo vesicles was 50-150 nm,and the exosome-specific marker proteins cluster of differentiation 63(CD63),cluster of differentiation 9(CD9),tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)were positively expressed,indicating successful exosome extraction.A549 cells efficiently took up PKH67-labeled Exo.The RT-PCR results showed that compared with A549 cells cultured alone,the expression level of lncRNA DUXAP8 in the A549 cells was increased after treatment with Exo derived from A549 cells(P<0.05).compared with control group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there were no significant difference in the expression level of IncRNA DUXAP8 in the cells in Exo+sh-NC group(P>0.05).The colony formation assay results showed that compared with control group,the number of colony formation of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the number of colony formation of the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the number of colony formation of the A549 cells in Exo+sh-NC group(P>0.05).The EdU staining results showed that compared with control group,the EdU-positive rate of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the EdU-positive rate in A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the EDU-positive rate in the cells in Exo+sh-NC group(P>0.05).The flow cytometry results showed that compared with control group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo group was decreased(P<0.05);compared with Exo group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo+sh-DUXAP8 group was increased(P<0.05),while there was no significant difference in the percentage of activated CD8+T lymphaytes in Exo+sh-NC group(P>0.05).The MTT assay results showed that compared with control group,the killing rate of human peripheral blood lymphocytes on the A549 cells in Exo group was decreased(P<0.05);compared with Exo group,the killing rate of human peripheral blood lymphocytes on A549 cells in Exo+sh-DUXAP8 group was increased(P<0.05),while no significant difference was observed in Exo+sh-NC group(P>0.05).Conclusion:The lncRNA DUXAP8 in exosomes derived from the lung cancer A549 cells promotes the proliferation of lung cancer cells and tumor immune escape.

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective To explore the effects of 1 800 MHz electromagnetic radiation(EMR)on cognitive function of 3xTg-AD and 57C mice,providing a theoretical basis for the potential impacts of electromagnetic radiation on the human body.Methods A total of 12 3xTg-AD transgenic mice and 12 wild-type C57 mice were selected as research subjects.The one-month-old mice were divided into four groups:RF WT,Control WT,RF AD,and Control AD,with 6 mice in each group.The 1 800 MHz EMR exposure experiments were conducted from 20:00 to 8:00 the next day for a duration of 5 months.After the exposure,a water maze test was conducted to evaluate the effects of EMR on spatial learning and memory abilities of 3xTg AD mice,along with measurements of body weight,brain weight,and calculation of the brain-to-body ratio.Finally,Western Blot technique was used to measure the levels of APP,NR1,and NR2A in hippocampal tissue to analyze effects of 1 800 MHz EMR on the cognitive function of 3xTg AD mice.Results Under 1 800 MHz EMR exposure,there were no statistically significant differences in Morris water maze spatial learning ability among the four groups(P>0.05).However,longer escape time,greater swimming distances,and more crossings of target quadrant were exhibited in the RF AD group compared to the other groups(P<0.05).Western Blot results showed that the APP protein levels in 3xTg AD mice was higher than those in C57 mice(P<0.05).The expression levels of NR1 protein in the WT group was higher than those in the AD group(P<0.05);in the AD group,the RF AD group had higher levels than the Control WT group(P<0.05),and the NR2A protein levels in the Control WT group were higher than in the other groups(P<0.05).Conclusion Prolonged exposure to 1 800 MHz EMR can affect the learning and cognitive function of both 3xTg AD and C57 mice.

Objective To investigate the effect of electromagnetic wave power density on the expression of glial fibrillary acidic protein(GFAP)in the hippocampus of SD rats under 1800 MHz electromagnetic wave irradiation,and whether it exhibits a"window effect".Methods Ninety-eight 4-week-old SPF-grade SD rats were randomly divided into 14 groups,with 7 rats in each group.Seven groups were exposed groups(frequency:1800 MHz,power densities:0.1 mW/cm2,0.3 mW/cm2,0.5 mW/cm2,0.7 mW/cm2,0.9 mW/cm2,1.0 mW/cm2,1.2 mW/cm2)and corresponding 7 groups were control groups(power density:0 mW/cm2).Exposure was conducted for 12 hours daily for 3 weeks.After exposure,Western Blot was used to detect the expression level of GFAP in the hippocampal tissue,and immunohistochemistry staining was performed to determine the average optical density(MOD)value of GFAP-positive expression products in the DG,CA3,and CA1 regions of the hippocampal tissue,to determine the power density window of GFAP expression in the hippocampus of SD rats under 1800 MHz exposure.Results At power densities of 0.1 mW/cm2 and 0.3 mW/cm2,Western Blot results showed increased expression of GFAP in the rat hippocampus(P<0.05),and immunohistochemistry staining demonstrated increased MOD values of GFAP in the three regions(P<0.05).Conclusion Long-term exposure to 1800 MHz elect-romagnetic radiation has a"window effect"on the expression of GFAP in the DG,CA3,and CA1 regions of the hippocampus in SD rats,with power density windows of 0.1 mW/cm2 and 0.3 mW/cm2.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.

Objective:To analyze the association between zygomatic change and bone setback or resection and propose a quantitative guidance for L-shaped reduction malarplasty by linear regression analysis based on computed tomographic (CT) scan images.Methods:A retrospective observational study was conducted on patients who underwent L-shaped reduction malarplasty with mortice and tenon joint at the zygomatic arch in Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2017 to September 2022. Bone setback and resection were performed in cases required a classical L-shaped osteoectomy with oblique bone resection (Group Ⅰ). Bone setback was performed in cases required a modified L-shaped osteotomy without bone resection (Group Ⅱ). Wound healing and the occurrence of complications were followed up after operation. The amount of bone setback and resection were calculated by using preoperative and postoperative CT scan images. The unilateral width changes of the anterior, middle, and posterior zygomatic regions(ΔZBP-MFP, ΔZMP-MFP, ΔZAP-MFP, respectively) as well as zygomatic protrusion change(Δzygomatic protrusion) were also evaluated. SPSS 20.0 software was used for statistical analysis. The measurement data was expressed as Mean±SD. Zygomatic width and protrusion change of the two groups was compared by independent t-test. Comparison of complication rates between the two groups was performed using the χ2 test. Correlation analysis using Pearson correlation coefficients was performed between bone resection or setback and zygomatic width or protrusion change. Linear regression analysis was also performed. Results:A total of 80 patients were enrolled. Group Ⅰ consisted of 40 patients [6 males and 34 females; aged (25.2±3.8) years, ranging from 19 to 33 years] who underwent a classical L-shaped osteotomy with both bone setback and resection, while Group Ⅱ consisted of 40 patients [10 males and 30 females; aged (26.0±3.0) years, ranging from 20 to 35 years] who underwent a modified L-shaped osteotomy with bone setback but without bone resection. All patients healed uneventfully during the follow-up period[(12.5±3.3) months, ranging from 5 to 20 months]. There was no significant difference in the incidence of complications such as infection, transient paresthesia, severe swelling and hematoma between the two groups ( P>0.05). No severe complications, such as facial asymmetry, sagging cheek, bone nonunion, were observed. All patients significantly improved facial contours. There was a statistically significant difference (all P<0.01) in ΔZBP-MFP [ (2.52±0.76) mm vs. (1.85±0.40) mm], ΔZMP-MFP [ (3.30±0.54) mm vs. (2.94±0.51) mm] and Δzygomatic protrusion [ (4.42±1.20) mm vs. (3.59±0.84) mm] between Group Ⅰ and Group Ⅱ. No statistical difference was found in ΔZAP-MFP ( P>0.05). Significant correlation was observed between the bone setback or resection and the changes of anterior, middle zygomatic width as well as protrusion in both the two groups ( r=0.60-0.92, all P<0.01), and the linear regression equation was established. The correlation between bone setback or resection and the posterior zygomatic width change was not significant ( P>0.05). Conclusion:There are linear correlations between the unilateral anterior, middle zygomatic width change, zygomatic protrusion change and the unilateral bone setback or resection. The linear regression equations can be used as a quantitative guidance for preoperative surgical planning.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.