Surufatinib combined with photodynamic therapy induces ferroptosis to inhibit cholangiocarcinoma in vitro and in tumor models.

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

Prognosis prediction and comparison between pancreatic signet ring cell carcinoma and pancreatic duct adenocarcinoma: a retrospective observational study.

Background: Pancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive cancer that has been reported primarily as case reports. Due to limited large-scale epidemiological and prognostic analyses, the outcomes of PSRCC patients varies greatly in the absence of recognized first-line treatment strategies. This study aimed to compare the clinical features, treatment, and prognosis of PSRCC and pancreatic ductal cell carcinoma (PDAC), the most common subtype of pancreatic cancer, and to establish predictive models for these subtypes. Methods: The data on PSRCC and PDAC patients from 1998 to 2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Thereafter, the clinical, demographic, and treatment characteristics of the two groups and the differences and influencing factors of the two groups were evaluated by propensity score matching (PSM), Kaplan-Meier survival curves, Cox risk regression analyses, and least absolute shrinkage and selection operator (LASSO) analysis. Next, prognosis models were constructed and validated by KM and ROC analysis. Finally, a nomogram was constructed, based on the results of these analyses, to predict survival outcomes of PSRCC and PDAC patients. Results: A total of 84,789 patients (432 PSRCC and 84357 PDAC patients) were included in this study. The results of the study revealed that, compared to the PDAC patients, PSRCC patients were more likely to be male, aged between 58-72 years, have larger tumor masses, and less likely to undergo chemotherapy. Before PSM, the overall survival and cancer-specific survival of the PSRCC group were significantly lower than those PDAC group, but there was no difference in the prognosis of the two groups after PSM. Additionally, lymph node ratio (LNR), log odds of positive lymph node (LODDS), tumor size, age, T-stage, marital status, and summary stage were found to be independent prognostic factors for PSRCC. Lastly, the prediction model and nomogram based on these prognostic factors could accurately predict the survival rate of the patients in SEER datasets and external validation datasets. Conclusion: The prognosis of PSRCC and PDAC patients is similar under the same conditions; however, PSRCC patients may have more difficulty in receiving better treatment, thus resulting in their poor prognosis.

A prediction model for moderate to severe cancer-related fatigue in colorectal cancer after chemotherapy: a prospective case‒control study.

AIMS: The study aims to develop a model to predict the risk of moderate to severe cancer-related fatigue (CRF) in colorectal cancer patients after chemotherapy. METHODS: The study population was colorectal cancer patients who received chemotherapy from September 2021 to June 2022 in a grade 3 and first-class hospital. Demographic, clinical, physiological, psychological, and socioeconomic factors were collected 1 to 2 days before the start of chemotherapy. Patients were followed up for 1 to 2 days after the end of chemotherapy to assess fatigue using the Piper Fatigue Scale. A random sampling method was used to select 181 patients with moderate to severe CRF as the case group. The risk set sampling method was used to select 181 patients with mild or no CRF as the control group. Logistic regression, back-propagation artificial neural network (BP-ANN), and decision tree models were constructed and compared. RESULTS: A total of 362 patients consisting of 241 derivation samples and 121 validation samples were enrolled. Comparing the three models, the prediction effect of BP-ANN was the best, with a receiver operating characteristic (ROC) curve of 0.83. Internal and external verification indicated that the accuracy of prediction was 70.4% and 80.8%, respectively. Significant predictors identified were surgery, complications, hypokalaemia, albumin, neutrophil percentage, pain (VAS score), Activities of Daily Living (ADL) score, sleep quality (PSQI score), anxiety (HAD-A score), depression (HAD-D score), and nutrition (PG-SGA score). CONCLUSIONS: BP-ANN was the best model, offering theoretical guidance for clinicians to formulate a tool to identify patients at high risk of moderate to severe CRF.

Intersection of nanomaterials and organoids technology in biomedicine.

Organoids are stem cell-derived, self-organizing, 3D structures. Compared to the conventional 2D cell culture method, 3D cultured organoids contain a variety of cell types that can form functional "micro-organs" and can be used to simulate the occurrence process and physiological pathological state of organ tissues more effectively. Nanomaterials (NMs) are becoming indispensable in the development of novel organoids. Understanding the application of nanomaterials in organoid construction can, therefore, provide researchers with ideas for the development of novel organoids. Here, we discuss the application status of NMs in various organoid culture systems and the research direction of NMs combined with organoids in the biomedical field.

Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients.

Objective: To identify the gene subtypes related to immune cells of cholangiocarcinoma and construct an immune score model to predict the immunotherapy efficacy and prognosis for cholangiocarcinoma. Methods: Based on principal component analysis (PCA) algorithm, The Cancer Genome Atlas (TCGA)-cholangiocarcinoma, GSE107943 and E-MTAB-6389 datasets were combined as Joint data. Immune genes were downloaded from ImmPort. Univariate Cox survival analysis filtered prognostically associated immune genes, which would identify immune-related subtypes of cholangiocarcinoma. Least absolute shrinkage and selection operator (LASSO) further screened immune genes with prognosis values, and tumor immune score was calculated for patients with cholangiocarcinoma after the combination of the three datasets. Kaplan-Meier curve analysis determined the optimal cut-off value, which was applied for dividing cholangiocarcinoma patients into low and high immune score group. To explore the differences in tumor microenvironment and immunotherapy between immune cell-related subtypes and immune score groups of cholangiocarcinoma. Results: 34 prognostic immune genes and three immunocell-related subtypes with statistically significant prognosis (IC1, IC2 and IC3) were identified. Among them, IC1 and IC3 showed higher immune cell infiltration, and IC3 may be more suitable for immunotherapy and chemotherapy. 10 immune genes with prognostic significance were screened by LASSO regression analysis, and a tumor immune score model was constructed. Kaplan-Meier (KM) and receiver operating characteristic (ROC) analysis showed that RiskScore had excellent prognostic prediction ability. Immunohistochemical analysis showed that 6 gene (NLRX1, AKT1, CSRP1, LEP, MUC4 and SEMA4B) of 10 genes were abnormal expressions between cancer and paracancer tissue. Immune cells infiltration in high immune score group was generally increased, and it was more suitable for chemotherapy. In GSE112366-Crohn's disease dataset, 6 of 10 immune genes had expression differences between Crohn's disease and healthy control. The area under ROC obtained 0.671 based on 10-immune gene signature. Moreover, the model had a sound performance in Crohn's disease. Conclusion: The prediction of tumor immune score model in predicting immune microenvironment, immunotherapy and chemotherapy in patients with cholangiocarcinoma has shown its potential for indicating the effect of immunotherapy on patients with cholangiocarcinoma.

Comprehensive Analysis of the Potential Immune-Related Biomarker ATG101 that Regulates Apoptosis of Cholangiocarcinoma Cells After Photodynamic Therapy.

Autophagy related gene 101 (ATG101) plays a significant role in the occurrence and development of tumours by responding to stress. Our research aims to illustrate the correlation between the expression of ATG101 and tumor prognosis and its potential role and mechanism in tumor immunity and photodynamic therapy (PDT). First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, Kaplan-Meier curves was applied in cholangiocarcinoma (CHOL) and liver hepatocellular carcinoma (LIHC) datasets for survival analysis. Next, the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints was analysed. Besides, the relationship between the expression of ATG101 and methyltransferase. GSEA was used to study the function and the related transcript factors of ATG101 in CHOL and LIHC. The effect of PDT on ATG101 was verified by microarray, qPCR and western blot. Then the effect of ATG101 and its regulatory factors on apoptosis were verified by siRNA, lentivirus transfection and Chip-qPCR. Comprehensive analysis showed that ATG101 was overexpressed in different tumours. Kaplan-Meier curves found that ATG101 was associated with poor prognosis in tumours (including CHOL and LIHC). We found that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in CHOL and LIHC. Subsequent validation tests confirmed that the up-regulated ATG101 after PDT treatment is not conducive to the occurrence of apoptosis of cholangiocarcinoma cells. The high expression of ATG101 may be induced by the early stress gene EGR2. Our study highlights the significance of ATG101 in the study of tumour immunity and photodynamic therapy from a pan-cancer perspective.

Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model.

Extracellular aggregation of amyloid-beta (Aß) and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer's disease. A linear interaction between Aß and tau protein has been characterized in several models. Aß induces tau hyperphosphorylation through a complex mechanism; however, the master regulators involved in this linear process are still unclear. In our study with Drosophila melanogaster, we found that Aß regulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase. Importantly, Aß toxicity was dependent on tau hyperphosphorylation, and flies with hypophosphorylated tau were insulated against Aß-induced toxicity. Strikingly, tau accumulation reciprocally interfered with Aß degradation and correlated with the reduction in mRNA expression of genes encoding Aß-degrading enzymes, including dNep1, dNep3, dMmp2, dNep4, and dIDE. Our results indicate that Aß and tau protein work synergistically to further accelerate Alzheimer's disease progression and may be considered as a combined target for future development of Alzheimer's disease therapeutics.

Novel perspective in pancreatic cancer therapy: Targeting ferroptosis pathway.

Pancreatic cancer is a highly lethal malignancy with low resection and survival rates and is not sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of nonapoptotic regulated cell death characterized by the accumulation of lipid peroxides and reactive oxygen species involved in iron metabolism. Ferroptosis has a significant role in the occurrence and development of various tumors. Previous studies have shown that regulating ferroptosis-induced cell death inhibited tumor growth in pancreatic cancer and was synergistic with other antitumor drugs to improve treatment sensitivity. Herein, we discuss the mechanism, inducers, and developments of ferroptosis in pancreatic cancer to provide new strategies for the treatment of the malignancy.

A Novel Ferroptosis-Related 4-Gene Prognostic Signature for Cholangiocarcinoma and Photodynamic Therapy.

Cholangiocarcinoma is the second most common malignant tumor in the hepatobiliary system. Compared with data on hepatocellular carcinoma, fewer public data and prognostic-related studies on cholangiocarcinoma are available, and effective prognostic prediction methods for cholangiocarcinoma are lacking. In recent years, ferroptosis has become an important subject of tumor research. Some studies have indicated that ferroptosis plays an important role in hepatobiliary cancers. However, the prediction of the prognostic effect of ferroptosis in patients with cholangiocarcinoma has not been reported. In addition, many reports have described the ability of photodynamic therapy (PDT), a potential therapy for cholangiocarcinoma, to regulate ferroptosis by generating reactive oxygen species (ROS). By constructing ferroptosis scores, the prognoses of patients with cholangiocarcinoma can be effectively predicted, and potential gene targets can be discovered to further enhance the efficacy of PDT. In this study, gene expression profiles and clinical information (TCGA, E-MTAB-6389, and GSE107943) of patients with cholangiocarcinoma were collected and divided into training sets and validation sets. Then, a model of the ferroptosis gene signature was constructed using least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. Furthermore, through the analysis of RNA-seq data after PDT treatment of cholangiocarcinoma, PDT-sensitive genes were obtained and verified by immunohistochemistry staining and Western blot. The results of this study provide new insight for predicting the prognosis of cholangiocarcinoma and screening target genes that enhance the efficacy of PDT.

Application and research progress of organoids in cholangiocarcinoma and gallbladder carcinoma.

Both cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are belong to biliary tract carcinomas (BTCs) with a high degree of malignancy and a poor prognosis. Therefore, an in vitro model is urgently needed to increase our understanding of the pathogenesis of BTCs. Tumor organoids are a novel three-dimensional (3D) culture technology that utilizes samples from removed tumors. Therefore, it can maintain the histological features, expression profiles and marker expression of the parental tissues. Recently, with the widespread use of this technique, increasing research is beginning to use organoid to study the cellular metabolism, pathogenesis, chemotherapy resistance, and new therapy methods of BTCs. In this review, we will discuss the advantages and disadvantages of BTC organoids compared with other cell culture techniques. In addition, the construction methods, research directions and current limitations of BTC organoids will be described.

Does oblique lumbar interbody fusion promote adjacent degeneration in degenerative disc disease: A finite element analysis.

BACKGROUND: The number of oblique lumbar interbody fusion (OLIF) procedures has continued to rise over recent years. Adjacent segment degeneration (ASD) is a common complication following vertebral body fusion. Although the precise mechanism remains uncertain, ASD has gradually become more common in OLIF. Therefore, the present study analyzed the association between disc degeneration and OLIF to explore whether adjacent degeneration was promoted by OLIF in degenerative disc disease. METHODS: A three-dimensional nonlinear finite element (FE) model of the L3-S1 lumbar spine was developed and validated. Three lumbar spine degeneration models with different degrees of degeneration (mild, moderate and severe) and a model of OLIF surgery were constructed at the L4-L5 level. When subjected to a follower compressive load (500 N), hybrid moment loading was applied to all models of the lumbar spine and the range of motion (ROM), intradiscal pressure (IDP), facet joint force (FJF), average mises stress in the annulus (AMSA), average tresca stress in the annulus (ATSA) and average endplate stress (AES) were measured. RESULTS: Compared with the healthy lumbar spine model, the ROM, IDP, FJF, AMSA, ATSA and AES of the segments adjacent to the degenerated segment increased in each posture as the degree of disc degeneration increased. In different directions of motion, the ROM, IDP, FJF, AMSA, ATSA and AES in the OLIF model in the L3-L4 and L5-S1 segments were higher than those of the healthy model and each degenerated model. Compared with the healthy model, the largest relative increase in biomechanical parameters above (ROM, IDP, FJF, AMSA, ATSA or AES) was observed in the L3-L4 segment in the OLIF model, of 77.13%, 32.63%, 237.19%, 45.36%, 110.92% and 80.28%, respectively. In the L5-S1 segment the corresponding values were 68.88%, 36.12%, 147.24%, 46.00%, 45.88% and 51.29%, respectively. CONCLUSIONS: Both degenerated discs and OLIF surgery modified the pattern of motion and load distribution of adjacent segments (L3-L4 and L5-S1 segments). The increases in the biomechanical parameters of segments adjacent to the surgical segment in the OLIF model were more apparent than those of the degenerated models. In summary, OLIF risked accelerating the degeneration of segments adjacent to those of a surgical segment.

Biomechanical Effect of L4 -L5 Intervertebral Disc Degeneration on the Lower Lumbar Spine: A Finite Element Study.

OBJECTIVE: To ascertain the biomechanical effects of a degenerated L4 -L5 segment on the lower lumbar spine through a comprehensive simulation of disc degeneration. METHODS: A three-dimensional nonlinear finite element model of a normal L3 -S1 lumbar spine was constructed and validated. This normal model was then modified such that three degenerated models with different degrees of degeneration (mild, moderate, or severe) at the L4 -L5 level were constructed. While experiencing a follower compressive load (500 N), hybrid moment loads were applied to all models to determine range of motion (ROM), intradiscal pressure (IDP), maximum von Mises stress in the annulus, maximum shear stress in the annulus, and facet joint force. RESULTS: As the degree of disc degeneration increased, the ROM of the L4 -L5 degenerated segment declined dramatically in all postures (flexion: 5.79°-1.91°; extension: 5.53°-2.62°; right lateral bending: 4.47°-1.46°; left lateral bending: 4.86°-1.61°; right axial rotation: 2.69°-0.74°; left axial rotation: 2.69°-0.74°), while the ROM in adjacent segments increased (1.88°-8.19°). The largest percent decrease in motion of the L4 -L5 segment due to disc degeneration was in right axial rotation (75%), left axial rotation (69%), flexion (67%), right lateral bending (67%), left lateral bending right (67%), and extension (53%). The change in the trend of the IDP was the same as that of the ROM. Specifically, the IDP decreased (flexion: 0.592-0.09 MPa; extension: 0.678-0.334 MPa; right lateral bending: 0.498-0.205 MPa; left lateral bending: 0.523-0.272 MPa; right axial rotation: 0.535-0.246 MPa; left axial rotation: 0.53-0.266 MPa) in the L4 -L5 segment, while the IDP in adjacent segments increased (0.511-0.789 MPa). The maximum von Mises stress and maximum shear stress of the annulus in whole lumbar spine segments increased (L4 -L5 segment: 0.413-2.626 MPa and 0.412-2.783 MPa, respectively; adjacent segment of L4 -L5 : 0.356-1.493 MPa and 0.359-1.718 MPa, respectively) as degeneration of the disc progressively increased. There was no apparent regularity in facet joint force in the degenerated segment as the degree of disc degeneration increased. Nevertheless, facet joint forces in adjacent healthy segments increased as the degree of disc degeneration increased (extension: 49.7-295.3 N; lateral bending: 3.5-171.2 N; axial rotation: 140.2-258.8 N). CONCLUSION: Degenerated discs caused changes in the motion and loading pattern of the degenerated segments and adjacent normal segments. The abnormal load and motion in the degenerated models risked accelerating degeneration in the adjacent normal segments. In addition, accurate simulation of degenerated facet joints is essential for predicting changes in facet joint loads following disc degeneration.

Effect of Spiral Nucleus Implant Parameters on the Compressive Biomechanics of Lumbar Intervertebral Disc.

OBJECTIVE: To determine the effect of spiral nucleus implant parameters on the biomechanical behavior of the lumbar intervertebral disc after nucleus replacement under compressive loading. METHODS: A finite element (FE) model of nucleus replacement in the L4-5 intervertebral disc was constructed. The effects of a spiral implant parameters, such as elasticity, size, and friction property, on the biomechanical behavior of the disc under a compressive load were determined. The effect of an implant with a sharp edge on disc biomechanics was also examined. The stress distribution and contact pressure on the endplate and AF, axial stiffness of disc, and annular bulge of the nucleus replacement models were investigated. RESULTS: Axial stiffness, annular bulge, and contact pressure were all insensitive to friction properties. Insertion of the spiral implant reversed the changes in the AF and endplates due to the removal of the nucleus. There was a positive correlation between axial stiffness and elasticity with implant size. Annular bulge was positively correlated with size but negatively correlated with elasticity. Compared with the base model, the implant with a sharp edge caused a decrease in disc axial stiffness but an increase in contact pressure on the AF in an annular bulge in the sagittal and coronal axis, respectively. CONCLUSIONS: A spiral implant may provide similar biomechanical behavior as a normal disc during compressive loading, with an optimal modulus of approximately 7 MPa. The spiral implant should fully conform to the nucleus cavity during replacement for the best biomechanical results.

Application of the Ethyl Acetate Extract of Cichorium as a Potential Photosensitizer in Photodynamic Therapy Induces Apoptosis and Autophagy in Colorectal Cancer Cell Lines via the Protein Kinase R-Like Endoplasmic Reticulum Kinase Pathway.

The present study aims to evaluate the effect of the ethyl acetate extract of Cichorium (EAEC) as a novel photosensitizer in photodynamic therapy (PDT) of colorectal carcinoma (CRC) HCT116 and SW620 cells. The absorption and fluorescence spectra of EAEC were measured using a UV-vis spectrophotometer and fluorescence spectrophotometer, respectively. EAEC-induced reactive oxygen species (ROS) production in HCT116 and SW620 cells was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and glutathione/glutathione disulfide (GSH/GSSG). The photo- and dark toxicities of EAEC were estimated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake and localization of EAEC were detected by confocal laser fluorescence microscopy. Annexin V-FITC/PI staining, Western blotting and immunofluorescence staining were used to assess apoptosis and autophagy. The antitumor activity of EAEC was confirmed in a xenograft model. Finally, effects on the PERK pathway were verified using qRT-PCR and Western blotting. EAEC displayed absorption and fluorescence emission peaks at 660 nm and 678 nm, respectively. EAEC induced ROS production in CRC cells. Assessment of dark toxicity showed that treatment with EAEC alone induced little cytotoxicity in CRC or normal cells but that EAEC-PDT induced significant photocytotoxicity in CRC cells in a time- and dose-dependent manner. After cellular uptake, EAEC was located in the mitochondria. Treatment with EAEC-PDT reduced xenograft tumor size. Further evaluation suggested that activation of the PERK pathway mediates these effects, as the apoptotic rate and autophagy flux increased markedly after EAEC-PDT. EAEC, a natural photosensitizer extracted from Cichorium, displays potential utility in PDT of CRC by targeting the PERK pathway.

TDP-43 specific reduction induced by Di-hydrophobic tags conjugated peptides.

TAR DNA binding protein 43 (TDP-43) is a key target in amyotrophic lateral sclerosis (ALS) treatment. Here, based on hydrophobic tagging strategy, we designed and synthesized a series of single or double hydrophobic tags conjugated peptides D1-D8. Among them, it was found that D4 displayed strongest ability to induce TDP-43 degradation in cells. D4 could reduce TDP-43 induced cytotoxicity. Besides, D4 could reduce TDP-43 levels in a transgenic drosophila model.

Preliminary experience in treating thoracic spinal tuberculosis via a posterior modified transfacet debridement, instrumentation, and interbody fusion.

BACKGROUND: Posterior transfacet approach has been proved to be a safe and effective access to treat thoracic disc herniation. However, the therapeutic effect and safety of modified transfacet approach for treating thoracic spinal tuberculosis (TST) has not been reported in the clinical literature. In this study, the clinical efficacy and safety of a single-stage posterior modified transfacet debridement, posterior instrumentation, and interbody fusion for treating TST were retrospectively evaluated. PATIENTS AND METHODS: From 2009 to 2014, 37 patients with TST underwent a posterior modified transfacet debridement, interbody fusion following posterior instrumentation, under the cover of 18 months of antituberculosis chemotherapy. The patients were evaluated preoperatively and postoperatively in terms of Frankel Grade, visual analog scale (VAS) pain score, kyphotic Cobb angle, and bony fusion. RESULTS: The follow-up time was 39.8 ± 5.1 months (29-50 months). No postoperative complication or recurrence of spinal tuberculosis was observed. Definitive bony fusion was achieved in all patients. At the final follow-up, 2 cases were rated as Frankel grade D, 35 as grade E. VAS was recovered from 8.4 ± 1.0 cm to 0.4 ± 0.8 cm. The kyphotic angles were corrected from 29.4 ± 10.9° to 17.6 ± 6.3°. Using the Kirkaldy-Willis criteria, functional outcome was excellent in 29 patients, good in 7, and fair in 1. CONCLUSIONS: Our preliminary results showed that single-stage posterior modified transfacet debridement, posterior instrumentation, and interbody fusion are effective and safe surgical options for treating TST.

Correction: Preserving Posterior Complex Can Prevent Adjacent Segment Disease following Posterior Lumbar Interbody Fusion Surgeries: A Finite Element Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0166452.].

Preserving Posterior Complex Can Prevent Adjacent Segment Disease following Posterior Lumbar Interbody Fusion Surgeries: A Finite Element Analysis.

OBJECTIVE: To investigate the biomechanical effects of the lumbar posterior complex on the adjacent segments after posterior lumbar interbody fusion (PLIF) surgeries. METHODS: A finite element model of the L1-S1 segment was modified to simulate PLIF with total laminectomy (PLIF-LAM) and PLIF with hemilaminectomy (PLIF-HEMI) procedures. The models were subjected to a 400N follower load with a 7.5-N.m moment of flexion, extension, torsion, and lateral bending. The range of motion (ROM), intradiscal pressure (IDP), and ligament force were compared. RESULTS: In Flexion, the ROM, IDP and ligament force of posterior longitudinal ligament, intertransverse ligament, and capsular ligament remarkably increased at the proximal adjacent segment in the PLIF-LAM model, and slightly increased in the PLIF-HEMI model. There was almost no difference for the ROM, IDP and ligament force at L5-S1 level between the two PLIF models although the ligament forces of ligamenta flava remarkably increased compared with the intact lumbar spine (INT) model. For the other loading conditions, these two models almost showed no difference in ROM, IDP and ligament force on the adjacent discs. CONCLUSIONS: Preserved posterior complex acts as the posterior tension band during PLIF surgery and results in less ROM, IDP and ligament forces on the proximal adjacent segment in flexion. Preserving the posterior complex during decompression can be effective on preventing adjacent segment degeneration (ASD) following PLIF surgeries.

Biomechanical response of lumbar facet joints under follower preload: a finite element study.

BACKGROUND: Facet joints play a significant role in providing stability to the spine and they have been associated with low back pain symptoms and other spinal disorders. The influence of a follower load on biomechanics of facet joints is unknown. A comprehensive research on the biomechanical role of facets may provide insight into facet joint instability and degeneration. METHOD: A nonlinear finite element (FE) model of lumbar spine (L1-S1) was developed and validated to study the biomechanical response of facets, with different values of follower preload (0 N,500 N,800 N,1200 N), under loadings in the three anatomic planes. In this model, special attention was paid to the modeling of facet joints, including cartilage layer. The asymmetry in the biomechanical response of facets was also discussed. A rate of change (ROC) and an average asymmetry factor (AAF) were introduced to explore and evaluate the preload effect on these facet contact parameters and on the asymmetry under different loading conditions. RESULTS: The biomechanical response of facets changed according to the loading condition. The preload amplified the facet force, contact area and contact pressure in flexion-extension; the same effect was observed on the ipsilateral facet while an opposite effect could be seen on the contralateral facet during lateral bending. For torsion loading, the preload increased contact area, decreased the mean contact pressure, but had almost no effect on facet force. However, all the effects of follower load on facet response became weaker with the increase of preload. The greatest asymmetry of facet response could be found on the ipsilateral side during lateral bending, followed by flexion, bending (contralateral side), extension and torsion. This asymmetry could be amplified by preload in the bending (ipsilateral), torsion loading group, while being reduced in the flexion group. CONCLUSIONS: An analysis combining patterns of contact pressure distribution, facet load, contact area and contact pressure can provide more insight into the biomechanical role of facets under various moment loadings and follower loads. The effect of asymmetry on facet joint response should be fully considered in biomechanical studies of lumbar spine, especially in post structures subjected to physiological loadings.

[Biomechanical effect of anterior lower tibiofibular ligament rupture on tibiotalar articular surface].

OBJECTIVE: To investigate the changes between pressure of trochlea of talus surface and distribution of area after anterior lower tibiofibular ligament rupture, and provide basis for treating anterior lower tibiofibular ligament rupture. METHODS: Six fresh adult ankle joint specimens (4 males and 2 females, ranging age from 25 to 60 years, with an average of 44.6 years) were adopted. The specimens were removed from skin and muscles, remained ankle joint capsule, medial and lateral ligaments and anteroinferior tibiofibular ligament. The ankle joint was fixed with a special fixture in neutral position. Pressure sensitive film (700 N axial load ) was respectively used to measure mean pressure, peak pressure and stress distribution area of the upper articular facet of talar trochlea of the normal ankle joint and the ankle joint with anterioinferior tibiofibular ligament rupture. RESULTS: The stress distribution areas of the control group and the ruptured group were respectively (367.8 +/- 54.0) mm2 and (386.0 +/- 53.7) mm2; the mean pressures were respectively (1.40 +/- 0.12) MPa and (1.70 +/- 0.35) MPa; the peak pressures were respectively (2.60 +/- 0.33) MPa and (3.20 +/- 0.32) MPa. The experimental results showed that the change in stress distribution area after anterioinferior tibiofibular ligament rupture was not significant (t = 0.021, P = -0.983). When stress distribution changed, the region of stress concentration transferred to poster lateral,and mean pressure (t = 4.140, P = 0.020) and peak pressure (t = 3.169, P = 0.010) increased significantly. CONCLUSION: When anterior lower tibiofibular ligament rupture occurs, mean pressure,peak pressure and stress distribution of pressure of trochlea of talus surface is changed, which may cause traumatic arthritis, and surgical treatment is considerably used to restore normal anatomy.