The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Therapeutic targeting at genome mutations of liver cancer by the insertion of HSV1 thymidine kinase through Cas9-mediated editing.

BACKGROUND: Liver cancer is one of the most lethal malignancies for humans. The treatment options for advanced-stage liver cancer remain limited. A new treatment is urgently needed to reduce the mortality of the disease. METHODS: In this report, we developed a technology for mutation site insertion of a suicide gene (herpes simplex virus type 1- thymidine kinase) based on type II CRISPR RNA-guided endonuclease Cas9-mediated genome editing to treat liver cancers. RESULTS: We applied the strategy to 3 different mutations: S45P mutation of catenin beta 1, chromosome breakpoint of solute carrier family 45 member 2-alpha-methylacyl-CoA racemase gene fusion, and V235G mutation of SAFB-like transcription modulator. The results showed that the herpes simplex virus type 1-thymidine kinase insertion rate at the S45P mutation site of catenin beta 1 reached 77.8%, while the insertion rates at the breakpoint of solute carrier family 45 member 2 - alpha-methylacyl-CoA racemase gene fusion were 95.1%-98.7%, and the insertion at V235G of SAFB-like transcription modulator was 51.4%. When these targeting reagents were applied to treat mouse spontaneous liver cancer induced by catenin beta 1S45P or solute carrier family 45 member 2-alpha-methylacyl-CoA racemase, the mice experienced reduced tumor burden and increased survival rate. Similar results were also obtained for the xenografted liver cancer model: Significant reduction of tumor volume, reduction of metastasis rate, and improved survival were found in mice treated with the targeting reagent, in comparison with the control-treated groups. CONCLUSIONS: Our studies suggested that mutation targeting may hold promise as a versatile and effective approach to treating liver cancers.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

Effect of different loads on facet joint motion during lumbar lateral bending in sitting position.

OBJECTIVE: To study the effect of weight-bearing on lumbar facet joint during lateral bending in sitting position. METHODS: Ten normal healthy people (5 males and 5 females) aged 25-39 years (mean 32 ± 4.29 years) were recruited. CT scanning was used to reconstruct the lumbar spine model, and then dual fluoroscopic image system (DFIS) was used to restore the lumbar facet joint movement in sitting position. Finally, the lumbar facet joint translation distance and rotation angle were measured. RESULTS: In L3-4 level, the displacement of right facet joint in Y-axis was the smallest at 0.05 ± 0.40 mm, the displacement of 0 kg left facet joint in X-axis was the largest at 1.68 ± 0.85 mm, and the rotation angle was - 0.57 ± 1.43° to 5.66 ± 2.70° at 10 kg; in L4-5 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, - 0.13 ± 0.91 mm, and the displacement of left facet joint in Z-axis was the largest at - 2.11 ± 0.88 mm, and the rotation angle was 0.21 ± 2.14° to 7.89 ± 2.59° at 10 kg; in L5-S1 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, - 0.17 ± 1.10 mm, and the displacement of 0 kg left facet joint in X-axis was the largest at 2.19 ± 2.28 mm, and the rotation angle was 0.03 ± 2.02° to 3.98 ± 0.37°. CONCLUSION: In sitting position, weight-bearing has certain influence on the displacement of facet joints during lumbar lateral bending movement, and this influence occurs simultaneously in translation and rotation; the left and right facet joints are not symmetrical during lumbar lateral bending movement.

Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells.

The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPSeq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPSeq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.

[Research progress in control strategies of biological clock disorder].

Circadian clock is an internal mechanism evolved to adapt to cyclic environmental changes, especially diurnal changes. Keeping the internal clock in synchronization with the external clock is essential for health. Mismatch of the clocks due to phase shift or disruption of molecular clocks may lead to circadian disorders, including abnormal sleep-wake cycles, as well as disrupted rhythms in hormone secretion, blood pressure, heart rate, body temperature, etc. Long-term circadian disorders are risk factors for various common critical diseases such as metabolic diseases, cardiovascular diseases, and tumor. To prevent or treat the circadian disorders, scientists have conducted extensive research on the function of circadian clocks and their roles in the development of diseases, and screened hundreds of thousands of compounds to find candidates to regulate circadian rhythms. In addition, melatonin, light therapy, exercise therapy, timing and composition of food also play a certain role in relieving associated symptoms. Here, we summarized the progress of both drug- and non-drug-based approaches to prevent and treat circadian clock disorders.

Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells.

The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate Long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPseq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection (UMAP) analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen (HLA) molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPseq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.

Fusion Gene Detection in Prostate Cancer Samples Enhances the Prediction of Prostate Cancer Clinical Outcomes from Radical Prostatectomy through Machine Learning in a Multi-Institutional Analysis.

Prostate cancer remains one of the most fatal malignancies in men in the United States. Predicting the course of prostate cancer is challenging given that only a fraction of prostate cancer patients experience cancer recurrence after radical prostatectomy or radiation therapy. This study examined the expressions of 14 fusion genes in 607 prostate cancer samples from the University of Pittsburgh, Stanford University, and the University of Wisconsin-Madison. The profiling of 14 fusion genes was integrated with Gleason score of the primary prostate cancer and serum prostate-specific antigen level to develop machine-learning models to predict the recurrence of prostate cancer after radical prostatectomy. Machine-learning algorithms were developed by analysis of the data from the University of Pittsburgh cohort as a training set using the leave-one-out cross-validation method. These algorithms were then applied to the data set from the combined Stanford/Wisconsin cohort (testing set). The results showed that the addition of fusion gene profiling consistently improved the prediction accuracy rate of prostate cancer recurrence by Gleason score, serum prostate-specific antigen level, or a combination of both. These improvements occurred in both the training and testing cohorts and were corroborated by multiple models.

Resveratrol Attenuates Ankylosing Spondylitis in Mice by Inhibiting the TLR4/NF-κB/NLRP3 Pathway and Regulating Gut Microbiota.

Ankylosing spondylitis (AS) is an autoimmune disease associated with disturbed gut microbiota. Currently, the treatments and outcomes of AS are not satisfactory. It is reported that resveratrol (RES) is a major phytoalexin with anti-inflammatory, antibacterial and some other pharmacological effects. However, there are no studies on the role of RES in AS. Therefore, this study aimed to explore the effect and mechanism of RES on AS. Proteoglycan and complete freund's adjuvant were used to conduct an AS mouse model, and then the AS mice were gavaged with RES (20 mg/kg and 50 mg/kg) daily for 4 weeks. Subsequently, the effect of RES on AS mice was assessed by detecting disease severity, inflammatory cytokines, NLRP3 inflammasome, TLR4/NF-κB pathway, intestinal mucosal barrier function, intestinal microbial barrier function. The assessment results indicated that RES could significantly relieve progression and severity of AS, inhibit the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-17A, interferon-γ), and promote the expression of anti-inflammatory cytokines (interleukin-4). RES intervention caused the inhibition of NLRP3 inflammasome and TLR4/NF-κB pathway. In terms of intestinal barrier function, experimental results found RES increased zonula occludens-1 and occludin expression, and additionally, changed the composition of the gut microbiota by increasing levels of Lactobacillus and Bifidobacterium and reducing levels of Enterococcus faecalis and Escherichia coli. Collectively, RES protects PG-induced AS mice by inhibiting inflammatory responses and TLR4/NF-κB/NLRP3 pathway, restoring intestinal mucosal barrier function, and regulating the composition of the gut microbiota. In other words, RES is a potential candidate for the treatment of AS.

HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression.

PURPOSE: To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma. METHODS: Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay. RESULT: HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50% and the number of cells that migrated through the transwell insert was greatly decreased. The cell invasion rate was also significantly reduced. Moreover, typical markers of epithelial-mesenchymal transition such as E-cadherin, were increased, while vimentin and α-SMA were decreased after HIF-1α knockdown. In contrast, overexpression of DEC1 reversed the effects of HIF-1α knockdown. Cell proliferation, migration, and invasion were partially recovered. The level of E-cadherin was decreased, while the level of vimentin and α-SMA was increased. In addition, the level of ß-catenin and LEF1 was downregulated after HIF-1α knockdown. The expression of MMP2 and MMP9 also declined. However, overexpression of DEC1 after HIF-1α knockdown partially reversed the expression pattern of these molecules. CONCLUSION: HIF-1α contributed to EMT and metastasis through activation of canonical ß-catenin signalling in choriocarcinoma and this process was dependent on DEC1. This study provides a new mechanism of HIF-1α in choriocarcinoma and suggests that intervention with DEC1 might be a promising therapeutic choice for choriocarcinoma.

Oncogenic Activity of Solute Carrier Family 45 Member 2 and Alpha-Methylacyl-Coenzyme A Racemase Gene Fusion Is Mediated by Mitogen-Activated Protein Kinase.

Chromosome rearrangement is one of the hallmarks of human malignancies. Gene fusion is one of the consequences of chromosome rearrangements. In this report, we show that gene fusion between solute carrier family 45 member 2 (SLC45A2) and alpha-methylacyl-coenzyme A racemase (AMACR) occurs in eight different types of human malignancies, with frequencies ranging from 45% to 97%. The chimeric protein is translocated to the lysosomal membrane and activates the extracellular signal-regulated kinase signaling cascade. The fusion protein promotes cell growth, accelerates migration, resists serum starvation-induced cell death, and is essential for cancer growth in mouse xenograft cancer models. Introduction of SLC45A2-AMACR into the mouse liver using a sleeping beauty transposon system and somatic knockout of phosphatase and TENsin homolog (Pten) generated spontaneous liver cancers within a short period. Conclusion: The gene fusion between SLC45A2 and AMACR may be a driving event for human liver cancer development.

Transcriptome and Exome Analyses of Hepatocellular Carcinoma Reveal Patterns to Predict Cancer Recurrence in Liver Transplant Patients.

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. Liver transplantation has been an effective approach to treat liver cancer. However, significant numbers of patients with HCC experience cancer recurrence, and the selection of suitable candidates for liver transplant remains a challenge. We developed a model to predict the likelihood of HCC recurrence after liver transplantation based on transcriptome and whole-exome sequencing analyses. We used a training cohort and a subsequent testing cohort based on liver transplantation performed before or after the first half of 2012. We found that the combination of transcriptome and mutation pathway analyses using a random forest machine learning correctly predicted HCC recurrence in 86.8% of the training set. The same algorithm yielded a correct prediction of HCC recurrence of 76.9% in the testing set. When the cohorts were combined, the prediction rate reached 84.4% in the leave-one-out cross-validation analysis. When the transcriptome analysis was combined with Milan criteria using the k-top scoring pairs (k-TSP) method, the testing cohort prediction rate improved to 80.8%, whereas the training cohort and the combined cohort prediction rates were 79% and 84.4%, respectively. Application of the transcriptome/mutation pathways RF model on eight tumor nodules from 3 patients with HCC yielded 8/8 consistency, suggesting a robust prediction despite the heterogeneity of HCC. Conclusion: The genome prediction model may hold promise as an alternative in selecting patients with HCC for liver transplant.

A study of three-dimensional reconstruction and printing models in two cases of soft tissue sarcoma of the thigh.

PURPOSE: The aim of our study was to demonstrate the value of three-dimensional (3D) reconstruction and three-dimensional printing (3DP) models in two cases of soft tissue sarcoma (STS) of the thigh. MATERIALS AND METHODS: Two patients with STS were recruited and underwent enhanced CT and MRI scans. Then, the 3D models were reconstructed and printed using the obtained data, and five experts were invited to assess the segmentation quality. In addition, 34 junior, intermediate and senior general surgeons were recruited to demonstrate the value of 3D models in preoperative planning and invited five surgeons to complete the assessment of 3D models-assisted intraoperative navigation. Finally, 32 interns were enrolled to explore the significance of 3D models in medical education. RESULTS: All experts agree with the accuracy of the 3D models. The application of 3D models in preoperative planning improved the understanding of general surgeons (P = 0.000, P = 0.000, P = 0.000). After the planning tools were exchanged between the two groups, senior surgeons in group A showed more significant improvements in performance than junior and intermediate surgeons in group A (P = 0.001, P = 0.006). Surgeons unanimously agree on the value of 3D models in intraoperative navigation. When applied for the education of medical interns, these models could enhance their understanding of pathologic anatomies (P = 0.036). CONCLUSION: In two operations for STS of the thigh with complex adjacencies, our study demonstrates that 3D models are of great value for preoperative planning, intraoperative navigation and medical education. More importantly, these models were more helpful to senior general surgeons.

Pten-NOLC1 fusion promotes cancers involving MET and EGFR signalings.

Inactivation of Pten gene through deletions and mutations leading to excessive pro-growth signaling pathway activations frequently occurs in cancers. Here, we report a Pten derived pro-cancer growth gene fusion Pten-NOLC1 originated from a chr10 genome rearrangement and identified through a transcriptome sequencing analysis of human cancers. Pten-NOLC1 fusion is present in primary human cancer samples and cancer cell lines from different organs. The product of Pten-NOLC1 is a nuclear protein that interacts and activates promoters of EGFR, c-MET, and their signaling molecules. Pten-NOLC1 promotes cancer proliferation, growth, invasion, and metastasis, and reduces the survival of animals xenografted with Pten-NOLC1-expressing cancer cells. Genomic disruption of Pten-NOLC1 induces cancer cell death, while genomic integration of this fusion gene into the liver coupled with somatic Pten deletion produces spontaneous liver cancers in mice. Our studies indicate that Pten-NOLC1 gene fusion is a driver for human cancers.

GLP-1R Agonist Liraglutide Attenuates Inflammatory Reaction and Neuronal Apoptosis and Reduces Early Brain Injury After Subarachnoid Hemorrhage in Rats.

Liraglutide, one of the glucagon-like peptide 1 receptor (GLP-1R) agonists, has been demonstrated to protect brain damage produced by ischemic stroke. However, it remains unknown whether liraglutide attenuates early brain injury after subarachnoid hemorrhage. The present study was performed to explore the effect of liraglutide on early brain injury after subarachnoid hemorrhage in rats, and further investigate the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation, then received subcutaneous injection with liraglutide (50 or 100 µg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, and Evans Blue extravasation were measured 24 h after SAH. Immunofluorescent staining was performed to detect the extent of microglial activation in rat brain 24 h after SAH. TUNEL staining was performed to evaluate neuronal apoptosis in rat brain of SAH. Expression of GLP-1R, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Bcl-2, Bax, and cleaved caspase-3 in rat brain were determined by western blot. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat brain was assessed by ELISA. Neurological dysfunction, brain water content, Evans Blue extravasation, microglial activation, and neuronal apoptosis were significantly reduced by GLP-1R agonist liraglutide. Expression of GLP-1R in rat brain was decreased after SAH, which is significantly elevated by liraglutide. Expression of inflammatory mediates like COX-2, iNOS, TNF-α, and IL-1ß was increased after SAH, which were significantly inhibited by liraglutide. Furthermore, SAH caused the elevated expression of pro-apoptotic factors Bax and cleaved caspase-3 in rat brain, both of which were inhibited by liraglutide. In addition, liraglutide reversed the expression of anti-apoptotic protein Bcl-2. Our results demonstrated that liraglutide reduces early brain injury and attenuates inflammatory reaction and neuronal apoptosis in rats of SAH. Liraglutide provides neuroprotection against SAH, which might be associated with the inhibition of inflammation and apoptosis.

[Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells].

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Risk factors of cage nonunion after anterior cervical discectomy and fusion.

The aim of our study was to explore risk factors of cage nonunion after anterior cervical discectomy and fusion (ACDF).295 patients underwent ACDF in our hospital between Jan. 2014 and Jan. 2017. Of them, 277 patients suffered cage union (union group, UG) after 6-month follow-up and 18 did not (nonunion group, NG). We collected possible factors including gender, history of smoking, alcohol, hypertension, heart disease, diabetes, body mass index, diagnose, and preoperative visual analog scale -neck, visual analog scale-arm, neck disability index (NDI) and Japanese Orthorpaedic Association, surgical duration, blood loss, fusion levels, superior fusion segment, angle of C2-C7, range of motion for C2-C7, C2-C7 sagittal vertical axis and T1 slope. We performed univariable and multivariable analysis to compare data in 2 groups.The rate of cage nonunion after ACDF was 6.1% (18 of 295) in our study. The outcome of univariable analysis showed that age (63.5 ±â€Š10.1), angle of C2-C7 (18.0 ±â€Š4.6), range of motion of C2-C7 (32.5 ±â€Š7.7), C2-C7 sagittal vertical axis (17.9 ±â€Š4.3) and T1 slope (22.1 ±â€Š5.3) were higher in NG than these (59.4 ±â€Š9.2, 16.2 ±â€Š4.5, 30.2 ±â€Š6.9,16.1 ±â€Š4.0, 20.9 ±â€Š4.9) in UG. Additionally, patients with osteoporosis had markedly higher rate of cage nonunion after ACDF than those without. What's more, the multivariable analysis implied the same results with univariable analysis.Many factors could predict cage nonunion after ACDF. Cervical sagittal parameters play an important role in cage nonunion after ACDF. We hope that we can provide some guidance for spine surgeon before performing ACDF.

Lateral ventriculo-peritoneal shunt treating delayed cerebrospinal fluid leak after cervical laminoplasty: Case report.

RATIONALE: Delayed cerebrospinal fluid (CSF) leak is a rare and terrible complication after cervical surgery, potentially causing morbidity or even threatening life. PATIENT CONCERNS: A 55-year-old Chinese male, with a history of hypertension for 8 years, complained of numbness and weakness of both upper limbs for 10 years. Strength of right upper limb triceps and wrist extensor muscle was slight weakness. Bilateral Hoffman sign was positive. Cervical magnetic resonance imaging (MRI) indicated multilevel cervical spondylotic myelopathy. We performed cervical laminoplasty for that patient on August 23, 2018. Nevertheless, he abruptly complained of dizziness and vision, but the wound condition was good. Cervical MRI showed delayed cerebrospinal fluid leak on October 15, 2018. DIAGNOSES: He was diagnosed with delayed CSF leak after cervical laminoplasty. INTERVENTIONS: We performed lateral ventriculo-peritoneal shunt (LVPS) for that patient on October 17, 2018. OUTCOMES: At 3-month follow-up, the treatment has a good outcome and there is no recurrence of clinical symptoms. LESSONS: Delayed CSF leak after cervical laminoplasty is rare. Once diagnosed, surgery is needed as soon as possible. LVPS has been proven an effective treatment for this server disease.