Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology* ; Animals ; Homocysteine ; Mice ; Macrophages/drug effects* ; Humans ; RAW 264.7 Cells ; Atherosclerosis/chemically induced* ; Apoptosis/genetics* ; Phagocytosis/genetics* ; Jurkat Cells ; Interleukin-1beta/genetics* ; Efferocytosis

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Objective:To investigate the effects of antibiotic treatment and antibiotics combined with surgery treatment on the prognosis of patients with infective endocarditis (IE).Methods:The clinical data and prognosis of all patients diagnosed as IE discharged from Shanghai Jiao Tong University Affiliated Sixth People′s Hospital from June 2011 to May 2021 were collected. There were 240 IE patients, divided into antibiotic treatment group and the antibiotics combined with surgery group according to the treatment methods. The clinical characteristics and prognosis of the IE patients were compared between the two groups, so as to investigate the timing of surgery for IE patients and to analyze the effects of the two treatment methods on the prognosis of IE patients.Statistical analysis methods including Wilcoxon rank sum test, chi-square test, Kaplan-Meier survival analysis and Cox regression analysis were used when appropriate.Results:Of the 240 patients with IE, 63 cases were only treated with antibiotics and 177 cases were treated with antibiotics combined with surgery. After propensity score matching (PSM), one-year mortality rate of the IE patients in the antibiotics combined with surgery group was 11.1%(4/36), which was significantly lower than that in the antibiotic treatment group (33.3%(12/36), χ2=5.14, P=0.023). The median values of left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD) and left ventricular fractional shortening (LVFS) in the antibiotics combined with surgery group were 59%, 47 mm and 31%, respectively, which were significantly lower than those before surgery (63%, 54 mm and 34%, respectively, Z=6.19, 9.36 and 6.11, respectively, all P<0.001). The most common surgical indication was moderate to severe heart failure, and there was no significant difference between the early operation group and the late operation group (both P>0.050). The one-year cumulative survival rate of antibiotics combined with surgery group was 94.9%, which was significantly higher than that in the antibiotic treatment group (83.2%, χ2=7.38, P=0.007). Heart failure and Pitt bacteremia scores≥4 were the independent risk factors for one-year all-cause death of the IE patients (hazard ratio ( HR)=5.668 and 19.392, respectively, both P<0.050). Hospital days and antibiotics combined with surgery were independent related factors for reducing the risks of one-year all-cause death ( HR=0.931 and 0.299, respectively, both P<0.050). Pitt bacteremia scores≥4 had the greatest impact on one-year prognosis of the IE patients. Conclusions:Surgery could significantly improve cardiac function and one-year prognosis of the IE patients. IE patients with heart failure and Pitt bacteremia score≥4 should be actively treated.

Objectives:To explore the feasibility of anterior medial fenestration approach in situ reduction and fixation in the treatment of PipkinⅠ and Ⅱ femoral head fractures,and to explore the clinical effect of this operation.Methods:Hips of two anti-corrosion adult specimens treated with formalin were dissected, then anatomical structures and directional characteristics of anterior medial main muscles,ligaments,blood vessels and nerves were observed.The anterior medial fenestration approach was performed on bilateral hips of four fresh frozen specimens to determine pulling direction of stripped muscles and ligaments required during operation,and to observe and analyze vascular and nerve traction protection directions exposed in the approach.Determine extent of exposure to the approach and assess feasibility of this approach.The clinical data of 12 patients with Pipkin Ⅰ and Ⅱ femoral head fractures who underwent in situ reduction and fixation of anterior medial fenestration at Department of Orthopaedics,Affiliated Hospital of Chengdu University from February 2016 to April 2018 were retrospectively analyzed.There were 3 males and 9 females with an age of 48.5 years(range:37 to 59 years).There were 8 cases of Pipkin type Ⅰ and 4 cases of Pipkin type Ⅱ.The operation time,blood loss,fracture healing time,last Thompson-Epstein evaluation and Harris score were observed.Results:Anterior medial fenestration approach to expose the femoral head in 4 bilateral hips with a total of 8 sides of fresh frozen specimens.The upper boundary of observation fenestration was pubic body (anterior acetabulum),and the outer upper boundary was iliacus and psoas muscle.The lateral boundary was rectus femoris and femoral vessels,the lower boundary was transverse branch of the medial femoral circumflex artery and vein.The medial boundary was pubis muscle,short adductor muscle and long adductor muscle.Pubofemoral and iliofemoral ligament were seen in fenestration. Four quadrants in front of femoral head in fenestration can be seen after cutting switch capsule active hip joint. In 12 patients with femoral head fracture,the operation time was 107.5 minutes(range:90 to 135 minutes),and the intraoperative bleeding volume was 115.0 ml(range:85 to 150 ml).The patients were followed up for 18.6 months(range:12 to 28 months).The fracture healing time of 12 patients was 144.2 days(range:120 to 180 days).The curative effect was evaluated according to Thompson-Epstein standard at the last follow-up:excellent in 6 cases,good in 4 cases and fair in 2 cases.At the last follow-up,the Harris score of hip joints was 85.1(range:75 to 93).Conclusions:Anterior medial fenestration in situ reduction and fixation surgery is feasible for the treatment of Pipkin Ⅰ and Ⅱ femoral head fractures. The short and midterm follow-up results reveal satisfactory effect.

Objectives:To explore the feasibility of anterior medial fenestration approach in situ reduction and fixation in the treatment of PipkinⅠ and Ⅱ femoral head fractures,and to explore the clinical effect of this operation.Methods:Hips of two anti-corrosion adult specimens treated with formalin were dissected, then anatomical structures and directional characteristics of anterior medial main muscles,ligaments,blood vessels and nerves were observed.The anterior medial fenestration approach was performed on bilateral hips of four fresh frozen specimens to determine pulling direction of stripped muscles and ligaments required during operation,and to observe and analyze vascular and nerve traction protection directions exposed in the approach.Determine extent of exposure to the approach and assess feasibility of this approach.The clinical data of 12 patients with Pipkin Ⅰ and Ⅱ femoral head fractures who underwent in situ reduction and fixation of anterior medial fenestration at Department of Orthopaedics,Affiliated Hospital of Chengdu University from February 2016 to April 2018 were retrospectively analyzed.There were 3 males and 9 females with an age of 48.5 years(range:37 to 59 years).There were 8 cases of Pipkin type Ⅰ and 4 cases of Pipkin type Ⅱ.The operation time,blood loss,fracture healing time,last Thompson-Epstein evaluation and Harris score were observed.Results:Anterior medial fenestration approach to expose the femoral head in 4 bilateral hips with a total of 8 sides of fresh frozen specimens.The upper boundary of observation fenestration was pubic body (anterior acetabulum),and the outer upper boundary was iliacus and psoas muscle.The lateral boundary was rectus femoris and femoral vessels,the lower boundary was transverse branch of the medial femoral circumflex artery and vein.The medial boundary was pubis muscle,short adductor muscle and long adductor muscle.Pubofemoral and iliofemoral ligament were seen in fenestration. Four quadrants in front of femoral head in fenestration can be seen after cutting switch capsule active hip joint. In 12 patients with femoral head fracture,the operation time was 107.5 minutes(range:90 to 135 minutes),and the intraoperative bleeding volume was 115.0 ml(range:85 to 150 ml).The patients were followed up for 18.6 months(range:12 to 28 months).The fracture healing time of 12 patients was 144.2 days(range:120 to 180 days).The curative effect was evaluated according to Thompson-Epstein standard at the last follow-up:excellent in 6 cases,good in 4 cases and fair in 2 cases.At the last follow-up,the Harris score of hip joints was 85.1(range:75 to 93).Conclusions:Anterior medial fenestration in situ reduction and fixation surgery is feasible for the treatment of Pipkin Ⅰ and Ⅱ femoral head fractures. The short and midterm follow-up results reveal satisfactory effect.

Objective: To study the influencing factors of fracture nonunion after intramedullary nailing for subtrochanteric fracture and construct a risk assessment model. Methods: A retrospective analysis was performed on 251 patients with intramedullary nail fractures of the femoral subtrochanteric fracture from February 2006 to January 2018. According to the different treatment time, the 251 patients included in this study were divided into the modeling group and the verification group. In the modeling group, postoperative fracture nonunion rate, general data, fracture related factors, surgical reduction related factors, mechanical and biological factors were calculated, and the influencing factors of fracture nonunion were screened by univariate analysis. Indicators with statistical differences in univariate analysis were analyzed using Logistic regression model for multivariate analysis to build the risk assessment model. The influencing factors were re-evaluated through the verification group, and the differentiation and calibration of the model were evaluated. Results: Fracture nonunion occurred in 34 of 149 patients in the modeling group. Among the 13 potential influencing factors, univariate analysis and logistic regression analysis showed that postoperative hip varus, intramedullary nail fixation failure and complete open reduction were the risk factors of fracture nonunion. Postoperative reduction of medial cortex was a protective factor for fracture nonunion, and a regression equation was established. Based on the logistic regression model, the Nomogram diagram was drawn. In the verification group, fracture nonunion occurred in 24 of 149 patients. The area under the ROC curve was AUC=0.883>0.7, indicating that there was a moderate differentiation to evaluate the occurrence of fracture nonunion after operation. The goodness of fit test: the H-L test (χ²=2.921, P=0.712) showed that the model had a good calibration. Conclusion The risk factors of fracture nonunion were hip varus, failure of intramedullary nail fixation and complete open reduction after intramedullary nailing of subtrochanteric fracture, and postoperative reduction of medial cortex was the protective factor. The risk assessment model has moderate differentiation and good calibration, which can provide reference for the risk assessment of fracture nonunion after subtrochanteric fracture operation.

The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.