ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.

Objective: To explore the alleviating effect of geniposide on ulcerative colitis (UC) and to investigate its potential mechanism. Methods: A UC mouse model was induced using 5% dextran sulfate sodium ( DSS) . These mice were randomly divided into 6 groups ( n = 8) : control group , model group , sulfasalazine group[ 100 mg/(kg ·d) ] , low-dose geniposide group[ 10 mg/(kg ·d) ] , medium-dose geniposide group[20 mg/(kg ·d) ] , and high-dose geniposide group[40 mg/( kg · d) ] . The mice were orally administered for consecutive 10 days . The colon length and mouse body mass were measured , and the colon mucosal damage index (CMDI) and disease activity index (DAI) were scored . The pathological changes in colon tissue were observed using hematoxylin-eosin (HE) staining. The reagent kits were used to measure the levels of malondialdehyde ( MDA) , myeloperoxidase (MPO) , catalase ( CAT) , and glutathione ( GSH) in colon tissue . The enzyme linked immunosorbent assay (ELISA) was used to analyze the expression levels of tumor necrosis factor-α ( TNF-α) , interleukin-6 ( IL-6) , and IL-1βin colon tissue . Western blot was used to detect the protein expression of mucin 1 (MUC-1) , occludin , IL-6 , p-JAK2 , and p-STAT3 in colon tissue . Results: Compared with the normal control group , the body mass and colon length of the model group mice significantly reduced . The expression of MUC-1 and occludin proteins sig- nificantly reduced (P < 0. 01) . The activities of CAT and SOD significantly reduced . DAI score and CMDI score significantly increased (P < 0. 01) . The expression levels of TNF-α, IL-6 , and IL-1βsignificantly increased (P < 0. 01) . The content of MPO and MDA significantly increased (P < 0. 01) . The expression of IL-6 , p-JAK2 and p- STAT3 proteins significantly increased ( P < 0. 01) . Compared with the model group , the body mass and colon length of mice in sulfasalazine group and geniposide medium and high-dose groups significantly increased (P < 0. 05 or P < 0. 01) , the expression of MUC-1 and occludin proteins increased (P < 0. 05 or P < 0. 01) , as well as the activity of CAT and SOD (P < 0. 05 or P < 0. 01) . DAI score and CMDI score in Sulfasalazine group and genipo- side medium and high-dose groups significantly reduced (P < 0. 05 or P < 0. 01) , as well as the expression levels of TNF-α, IL-6 , and IL-1β(P < 0. 05 or P < 0. 01) . MPO and MDA content in Sulfasalazine group and genipo- side medium and high-dose groups significantly reduced (P < 0. 05 or P < 0. 01) , as well as the expression of IL- 6 , p-JAK2 , and p-STAT3 proteins (P < 0. 05 or P < 0. 01) . Conclusion Geniposide maintaines intestinal home- ostasis by regulating the structure of the intestinal flora and improves colitis injury in UC mice by inhibiting the acti- vation of the IL-6/JAK2/STAT3 pathway.

Objective This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest(RF)and artificial neural network(ANN).Methods GSE-33774,GSE106090,and GSE57631 datasets were obtained from the GEO database.The GSE33774 and GSE106090 da-tasets were analyzed for differential expression and functional enrichment.The protein-protein interaction networks(PPI)and RF screened vital genes.A diagnostic model for peri-implantitis was established using ANN and validated on the GSE33774 and GSE57631 datasets.A transcription factor-gene interaction network and a transcription factor-micro-RNA(miRNA)regulatory network were also established.Results A total of 124 differentially expressed genes(DEGs)involved in the regulation of peri-implantitis were screened.Enrichment analysis showed that DEGs were mainly associated with immune receptor activity and cytokine receptor activity and were mainly involved in processes such as leukocyte and neutrophil migration.The PPI and RF screened six essential genes,namely,CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8.The receiver oper-ating characteristic curve(ROC)indicated that the ANN model had an excellent diagnostic performance.FOXC1,GA-TA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 may be a key miRNA.Con-clusion The diagnostic model of peri-implantitis constructed by RF and ANN has high confidence,and CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8 are potential diagnostic markers.FOXC1,GATA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 plays a vital role as a critical miRNA.

Objective This study aims to investigate the role of genes related to fatty acid metabolism in periodon-titis through machine learning and bioinformatics methods.Methods Periodontitis datasets GSE10334 and GSE-16134 were downloaded from the GEO database,and the fatty acid metabolism-related gene sets were obtained from the GeneCards database.Differentially expressed fatty acid metabolism-related genes(DEFAMRGs)in periodontitis were screened using the"limma"R package.Functional enrichment and pathway analyses were conducted.Recursive Feature Elimination,Least Absolute Shrinkage and Selection Operator,and Boruta algorithm were used to determine hub DEFAMRGs and construct diagnostic models with internal and external validation.Subtypes of periodontitis relat-ed to hub DEFAMRGs were constructed using consis-tency clustering analysis.CIBERSORT was used to ana-lyze immune cell infiltration in gingival tissues and ex-plore the correlation between hub DEFAMRGs and im-mune cells.Results A total of 113 periodontitis DE-FAMRGs were screened out as a result.The enrichment analysis results indicate that DEFAMRGs are mainly associat-ed with immune inflammatory responses and immune cell chemotaxis.Finally,8 hub DEFAMRGs(BTG2,CXCL12,FABP4,CLDN10,PPBP,RGS1,LGALSL,and RIF1)were identified and a diagnostic model(AUC=0.967)was con-structed,based on which periodontitis was divided into two subtypes.In addition,there is a significant correlation be-tween hub DEFAMRGs and different immune cell populations,with mast cells and dendritic cells showing higher cor-relation.Conclusion This study provides new insights and ideas for the occurrence and development mechanism of periodontitis and proposes a diagnostic model based on hub DEFAMRGs to provide new directions for diagnosis and treatment.

Objective:To investigate the clinical characteristics and prognosis of silicosis complicated with cavity-pulmonary tuberculosis.Methods:The clinical data of 63 patients with silicosis complicated with cavity-pulmonary tuberculosis (group A) and silicosis patients (group B) admitted to Yantaishan Hospital from July 2018 to July 2022 were collected and analyzed.Results:Patients in group A were all male, and the common symptoms were cough, expectoration, chest tightness, shortness of breath, and hemoptysis. CT cavity lesions involving the lung, often occurs in the lung after the tip section, after the back section and basal segment, thick-walled cavity, may be accompanied by satellite lesions, endobronchial spread focal, pneumothorax, pleural effusion, etc. 1225 cases of group B patients haemoptysis of 59 patients, cavity in 3 patients, haemoptysis and/or cavity rate was lower than that in group A, the difference was statistically significant ( P<0.05) . In group A, CT reexamination 6-24 months after anti-tuberculosis treatment showed that 52 cases (82.5%) had cavity reduction/healing, 8 cases (12.7%) had recurrence, and 3 cases (4.8%) had damaged lung (2 died) . Conclusion:Silicosis patients with hemoptysis and/or CT in cavity should be more vigilant about combined tuberculosis, anti-tuberculosis treatment and/or dynamic CT follow-up helps laboratory diagnosis negative patients.

Invasive pulmonary aspergillosis is the most common type of pulmonary aspergillosis. This paper reported a patient with pulmonary aspergillosis secondary to obstructive pulmonary disease and other underlying diseases. The clinical manifestations included wheezing, cough, fever and wheezing rale in the lungs. Diagnosis was ultimately confirmed through pathogens targeted next generation sequencing and pathological examination of respiratory coughs. Following comprehensive treatment that included antifungal therapy, the patient was cured and discharged with a good prognosis.

BACKGROUND:Calcaneal defects are common in clinical practice.It is difficult for surgeons to evaluate the effect of calcaneal reconstruction due to the complex anatomical structure and motor function of the heel.Finite element analysis has become an effective method for biomechanical behavior simulation and numerical analysis. OBJECTIVE:To compare the clinical effect and biomechanical characteristics of total calcaneal reconstruction with the Ⅱ-shaped and V-shaped fibular flap. METHODS:CT images of one left foot of a healthy 50-year-old male were acquired.Mimics software was used to obtain the preliminary three-dimensional model.Geomagic software was used to trim and curve the model.The model was imported into Solidworks software to simulate calcaneal reconstruction and complete the pre-processing of finite element calculation.Finally,Ansys software was used to solve the problem.The simulation results were compared with previous literature results to verify the effectiveness of the model.The surgical effect and biomechanical characteristics of the foot in different gait phases based on the simulated stress results were analyzed. RESULTS AND CONCLUSION:(1)Both Ⅱ-shaped and V-shaped fibular flaps could be used to reconstruct completely missing calcaneus,which could restore the length,width and height of normal calcaneus,and fill up the missing calcaneus bone.(2)Compared with the normal calcaneus,both configurations of fibular flaps showed a tendency for over-concentration of stress after loading.The normal calcaneus stress was mostly concentrated around the calcaneus nodule,the subtalar process and the calcaneus groove,while the stress of the two fibular flaps was mostly concentrated at the junction between the bone flap with the talus and cuboid bones.(3)The maximum stress of calcaneus was different between the two models and normal calcaneus under different simulation conditions,with statistically significant differences(P＜0.05).Compared with the V-shaped fibular flaps,Ⅱ-shaped fibular flaps had less force change in different gaits and were closer to the normal calcaneus.The V-shaped fibular flap bore excessive stress during the period of push-off,and the grafted bone material may yield under this condition and have the risk of fractures.

BACKGROUND:It has been found that vascular endothelial growth factor 165 and bone morphogenetic proteins interact with each other during hypoxia-reoxygenation and are involved in the repair process of osteoblast injury by regulating the activation of intracellular signaling pathways. OBJECTIVE:To further investigate the relationship between vascular endothelial growth factor 165/bone morphogenetic protein and hypoxic-reoxygenated osteoblast injury. METHODS:Osteoblasts were selected and the hypoxic-reoxygenated injury model was established.Vascular endothelial growth factor 165 and bone morphogenetic protein expressions at mRNA and protein levels were detected by real-time PCR and western blot before and after modeling.After modeling,osteoblasts were given different concentrations of vascular endothelial growth factor 165 and bone morphogenetic protein 2(10,20,40 ng/mL).Cell proliferation was detected by cell counting kit-8 method and apoptosis was detected by DAPI at 12,24,36,48,and 72 hours after treatment. RESULTS AND CONCLUSION:Compared with before modeling,the mRNA and protein expressions of vascular endothelial growth factor 165 and bone morphogenetic protein 2 in osteoblasts after modeling were significantly decreased(P＜0.05).The proliferation rate of osteoblasts was significantly increased with the increase of vascular endothelial growth factor 165 concentration(P＜0.05),while the apoptosis rate of osteoblasts decreased significantly with the increase of vascular endothelial growth factor 165 concentration(P＜0.05).The proliferation rate of osteoblast was significantly increased with the increase of bone morphogenetic protein 2 concentration(P＜0.05),while the apoptosis rate of osteoblast decreased significantly with the increase of bone morphogenetic protein 2 concentration(P＜0.05).To conclude,vascular endothelial growth factor 165 and bone morphogenetic protein are lowly expressed in hypoxic-reoxygenated osteoblast injury,and treatment with vascular endothelial growth factor 165 and bone morphogenetic protein can reduce the injury of hypoxic-reoxygenated osteoblast in a concentration-dependent manner,suggesting that vascular endothelial growth factor 165 and bone morphogenetic protein have a significant protective effect against the injury of hypoxic-reoxygenated osteoblasts.