The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation.

BACKGROUND: Intervertebral disc degeneration (IVDD) is an essential cause of low back pain (LBP), the incidence of which has risen in recent years and is progressively younger, but treatment options are limited, placing a serious economic burden on society. Sanbi decoction (SBD) is an important classical formula for the treatment of IVDD, which can significantly improve patients' symptoms and is a promising alternative therapy. PURPOSE: The aim of this study is to investigate the safety and efficacy of SBD in the treatment of IVDD and to explore the underlying mechanisms by using an integrated analytical approach of microbiomics and serum metabolomics, as well as by using molecular biology. METHODS: A rat IVDD puncture model was established and treated by gavage with different concentrations of SBD, and clean faeces, serum, liver, kidney, and intervertebral disc (IVD) were collected after 4 weeks. We assessed the safety by liver and kidney weighing, functional tests and tissue staining, the expression of tumor necrosis factor-alpha (TNF-ɑ), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) inflammatory factors in serum was detected by ELISA kits, and X-ray test, magnetic resonance imaging (MRI) examination, immunohistochemistry (IHC), western blotting (WB), hematoxylin-eosin (HE) staining and safranin O-fast green (SO/FG) staining were used to assess the efficacy. Finally, we performed 16S rRNA sequencing analysis on the faeces of different groups and untargeted metabolomics on serum and analyzed the association between them. RESULTS: SBD can effectively reduce the inflammatory response, regulate the metabolic balance of extracellular matrix (ECM), improve symptoms, and restore IVD function. In addition, SBD can significantly improve the diversity of intestinal flora and maintain the balance. At the phylum level, SBD greatly increased the relative abundance of Patescibacteria and Actinobacteriota and decreased the relative abundance of Bacteroidota. At the genus level, SBD significantly increased the relative abundance of Clostridia_UCG-014, Enterorhabdus, and Adlercreutzia, and decreased the relative abundance of Ruminococcaceae_UCG-005 (p < 0.05). Untargeted metabolomics indicated that SBD significantly improved serum metabolites and altered serum expression of 4alpha-phorbol 12,13-didecanoate (4alphaPDD), euscaphic acid (EA), alpha-muricholic acid (α-MCA), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (Kyn) (p < 0.05), and the metabolic pathways were mainly lipid metabolism and amino acid metabolism. CONCLUSIONS: This study demonstrated that SBD can extensively regulate intestinal flora and serum metabolic homeostasis to reduce inflammatory response, inhibit the degradation of ECM, restore IVD height and water content to achieve apparent therapeutic effect for IVDD.

Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically: an in silico study.

BACKGROUND: The capsule of the zygapophyseal joint plays an important role in motion segmental stability maintenance. Iatrogenic capsule injury is a common phenomenon in posterior approach lumbar interbody fusion operations, but whether this procedure will cause a higher risk of adjacent segment degeneration acceleration biomechanically has yet to be identified. METHODS: Posterior lumbar interbody fusion (PLIF) with different grades of iatrogenic capsule injury was simulated in our calibrated and validated numerical model. By adjusting the cross-sectional area of the capsule, different grades of capsule injury were simulated. The stress distribution on the cranial motion segment was computed under different loading conditions to judge the potential risk of adjacent segment degeneration acceleration. RESULTS: Compared to the PLIF model with an intact capsule, a stepwise increase in the stress value on the cranial motion segment can be observed with a step decrease in capsule cross-sectional areas. Moreover, compared to the difference between models with intact and slightly injured capsules, the difference in stress values was more evident between models with slight and severe iatrogenic capsule injury. CONCLUSION: Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically, and iatrogenic capsule damage on the cranial motion segment should be reduced to optimize patients' long-term prognosis.

Characteristics of Sagittal Alignment in Patients with Severe and Rigid Scoliosis.

OBJECTIVE: There has been increasing concern about the importance of sagittal alignment in the evaluation and treatment of spinal scoliosis. However, recent studies have only focused on patients with mild to moderate scoliosis. To date, little is known about the sagittal alignment in patients with severe and rigid scoliosis (SRS). This study was performed to evaluate the sagittal alignment in patients with SRS, and to analyze how it was altered after corrective surgery. METHODS: In this retrospective cohort study, we included 58 patients with SRS who underwent surgery from January 2015 to April 2020. Preoperative and postoperative radiographs were reviewed, and the sagittal parameters mainly included thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacrum slope (SS), and sagittal vertical axis (SVA). The sagittal balance state was evaluated according to whether the PI minus the LL (PI-LL) was less than 9°, and the patients were divided into thoracic hyperkyphosis and normal groups based on whether the TK exceeded 40°. The Student's t test, Pearson's test, and Receiver operating characteristic (ROC) curve analysis were used to compare related parameters between the different groups. RESULTS: The mean follow-up duration was 2.8 years. Preoperatively, the mean PI was 43.6 ± 9.4°, and the mean LL was 65.2 ± 13.9°. Sixty-nine percent of patients showed sagittal imbalance, and they showed larger TK and LL values and smaller PI and SVA values than those with sagittal balance. Additionally, most patients (44/58) presented with thoracic hyperkyphosis; this group had smaller PI and SVA values than the normal patients. Patients with syringomyelia-associated scoliosis were more likely to present with thoracic hyperkyphosis. The TK and LL values were significantly decreased, and 45% of patients with preoperative sagittal imbalance recovered after surgery. These patients had a larger PI (46.4 ± 9.0° vs 38.3 ± 8.8°, P = 0.003) and a smaller TK (25.5 ± 5.2° vs 36.3 ± 8.0°, P = 0.000) at the final follow-up. CONCLUSION: Preoperative sagittal imbalance appears in the majority of SRS patients, accounting for approximately 69% of our cohort. Patients with small PI values or syringomyelia-associated scoliosis were more likely to present with thoracic hyperkyphosis. Sagittal imbalance can generally be corrected by surgery, except in patients with a PI less than 39°. To achieve good postoperative sagittal alignment, we recommend controlling the TK to within 31°.

Fixation-induced surgical segment's high stiffness and the damage of posterior structures together trigger a higher risk of adjacent segment disease in patients with lumbar interbody fusion operations.

BACKGROUND: Adjacent segment disease (ASD) is a commonly reported complication after lumbar interbody fusion (LIF); changes in the mechanical environment play an essential role in the generation of ASD. Traditionally, fixation-induced high stiffness in the surgical segment was the main reason for ASD. However, with more attention paid to the biomechanical significance of posterior bony and soft structures, surgeons hypothesize that this factor may also play an important role in ASD. METHODS: Oblique and posterior LIF operations have been simulated in this study. The stand-alone OLIF and OLIF fixed by bilateral pedicle screw (BPS) system have been simulated. The spinal process (the attachment point of cranial ligamentum complex) was excised in the PLIF model; the BPS system has also been used in the PLIF model. Stress values related to ASD have been computed under physiological body positions, including flexion, extension, bending, and axial rotations. RESULTS: Compared to the stand-alone OLIF model, the OLIF model with BPS fixation suffers higher stress values under extension body position. However, there are no apparent differences under other loading conditions. Moreover, significant increases in stress values can be recorded in flexion and extension loading conditions in the PLIF model with posterior structures damage. CONCLUSIONS: Fixation-induced surgical segment's high stiffness and the damage of posterior soft tissues together trigger a higher risk of ASD in patients with LIF operations. Optimizing BPS fixation methods and pedicle screw designs and reducing the range of posterior structures excision may be an effective method to reduce the risk of ASD.

Regional differences in bone mineral density biomechanically induce a higher risk of adjacent vertebral fracture after percutaneous vertebroplasty: a case-comparative study.

BACKGROUND: Adjacent vertebral fracture (AVF) is a frequently observed complication after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compressive fracture. Biomechanical deterioration initially induces a higher risk of AVF. Studies demonstrated that the aggravation of regional differences in the elastic modulus of different components might deteriorate the local biomechanical environment and increase the risk of structural failure. Considering the existence of intravertebral regional differences in bone mineral density (BMD) (i.e. elastic modulus), it was hypothesized in the present study that higher intravertebral BMD differences may induce a higher risk of AVF biomechanically. MATERIALS AND METHODS: The radiographic and demographic data of osteoporotic vertebral compressive fracture patients treated using PVP were reviewed in the present study. The patients were divided into two groups: those with AVF and those without AVF. The Hounsfield unit (HU) values of transverse planes from the superior to the inferior bony endplate were measured, and the differences between the highest and lowest HU values of these planes were considered the regional differences of the HU value. The data from patients with and without AVF were compared, and the independent risk factors were identified through regression analysis. PVP with different grades of regional differences in the elastic modulus of the adjacent vertebral body was simulated using a previously constructed and validated lumbar finite element model, and the biomechanical indicators related to AVF were computed and recorded in surgical models. RESULTS: Clinical data on 103 patients were collected in this study (with an average follow-up period of 24.1 months). The radiographic review revealed that AVF patients present a significantly higher regional difference in the HU value and that the increase in the regional difference of the HU value was an independent risk factor for AVF. In addition, numerical mechanical simulations recorded a stress concentration tendency (the higher maximum equivalent stress value) in the adjacent vertebral cancellous bone, with a stepwise aggravation of the adjacent cancellous bony regional stiffness differences. CONCLUSIONS: The aggravation of regional BMD differences induces a higher risk of AVF after PVP surgery through a deterioration of the local biomechanical environment. The maximum differences in the HU value of the adjacent cancellous bone should, therefore, be measured routinely to better predict the risk of AVF. Patients with noticeable regional BMD differences should be considered at high risk for AVF, and greater attention must be paid to these patients to reduce the risk of AVF. EVIDENCE GRADE: Level III b.

Incidence and Risk Factors for Postoperative Ileus after Posterior Surgery in Adolescent Idiopathic Scoliosis.

OBJECTIVE: Postoperative ileus (POI) is a relatively common complication after spinal fusion surgery, which can lead to delayed recovery, prolonged length of stay and increased medical costs. However, little is known about the incidence and risk factors of POI after corrective surgery for patients with adolescent idiopathic scoliosis (AIS). This study was performed to report the incidence of POI and identify the independent risk factors for POI after postoperative corrective surgery. METHODS: In this retrospective cohort study, A total of 318 patients with AIS who underwent corrective surgery from April 2015 to February 2021 were enrolled and divided into two groups: those with POI and those without POI. The Student's t test, Mann-Whitney U test, and Pearson's chi-square test were used to compare the two groups regarding patient demographics and preoperative characteristics (age, sex and the major curve type), intraoperative and postoperative parameters (lowest instrumented vertebra [LIV], number of screws, and length of stay), radiographic parameters (T5-12 thoracic kyphosis [TK], T10-L2 thoracolumbar kyphosis and height [TLK and T10-L2 height], L1-S1 lumbar lordosis [LL], and L1-5 height). Then, a multivariate logistic regression analysis was used to identify independent risk factors for POI, and a receiver operating characteristic (ROC) curve was performed to assess the predictive values of these risk factors. RESULTS: Forty-two (13.2%) of 318 patients who developed POI following corrective surgery were identified. The group with POI had a significantly longer length of stay, more lumbar screws, higher proportions of a major lumbar curve and lumbar anterior screw breech, and a lower LIV. Among radiographic parameters, the mean lumbar Cobb angle at baseline, the changes in the lumbar Cobb angle, and T10-L2 and L1-5 height from before to after surgery were significantly larger in the group with POI than in the group without POI. Multivariate logistic regression analysis showed that large changes in T10-L2 (odds ratio [OR] =2.846, P = 0.007) and L1-5 height (OR = 31.294, p = 0.000) and lumbar anterior screw breech (OR = 5.561, P = 0.006) were independent risk factors for POI. The cutoff values for the changes in T10-L2 and L1-5 height were 1.885 cm and 1.195 cm, respectively. CONCLUSION: In this study, we identified that large changes in T10-L2 and L1-5 height and lumbar anterior screw breech were independent risk factors for POI after corrective surgery. Improving the accuracy of pedicle screw placement might reduce the incidence of POI, and greater attention should be given to patients who are likely to have large changes in T10-L2 and L1-5 height after corrective surgery.

TGFB2-AS1 inhibits triple-negative breast cancer progression via interaction with SMARCA4 and regulating its targets TGFB2 and SOX2.

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype for its high rates of relapse, great metastatic potential, and short overall survival. How cancer cells acquire metastatic potency through the conversion of noncancer stem-like cells into cancer cells with stem-cell properties is poorly understood. Here, we identified the long noncoding RNA (lncRNA) TGFB2-AS1 as an important regulator of the reversibility and plasticity of noncancer stem cell populations in TNBC. We revealed that TGFB2-AS1 impairs the breast cancer stem-like cell (BCSC) traits of TNBC cells in vitro and dramatically decreases tumorigenic frequency and lung metastasis in vivo. Mechanistically, TGFB2-AS1 interacts with SMARCA4, a core subunit of the SWI/SNF chromatin remodeling complex, and results in transcriptional repression of its target genes including TGFB2 and SOX2 in an in cis or in trans way, leading to inhibition of transforming growth factor ß (TGFß) signaling and BCSC characteristics. In line with this, TGFB2-AS1 overexpression in an orthotopic TNBC mouse model remarkably abrogates the enhancement of tumor growth and lung metastasis endowed by TGFß2. Furthermore, combined prognosis analysis of TGFB2-AS1 and TGFß2 in TNBC patients shows that high TGFB2-AS1 and low TGFß2 levels are correlated with better outcome. These findings demonstrate a key role of TGFB2-AS1 in inhibiting disease progression of TNBC based on switching the cancer cell fate of TNBC and also shed light on the treatment of TNBC patients.

Poor bone mineral density aggravates adjacent segment's motility compensation in patients with oblique lumbar interbody fusion with and without pedicle screw fixation: An in silico study.

Objective: Motility compensation increases the risk of adjacent segment diseases (ASDs). Previous studies have demonstrated that patients with ASD have a poor bone mineral density (BMD), and changes in BMD affect the biomechanical environment of bones and tissues, possibly leading to an increase in ASD incidence. However, whether poor BMD increases the risk of ASD by aggravating the motility compensation of the adjacent segment remains unclear. The present study aimed to clarify this relationship in oblique lumbar interbody fusion (OLIF) models with different BMDs and additional fixation methods. Methods: Stand-alone (S-A) OLIF and OLIF fixed with bilateral pedicle screws (BPS) were simulated in the L4-L5 segment of our well-validated lumbosacral model. Range of motions (ROMs) and stiffness in the surgical segment and at the cranial and caudal sides' adjacent segments were computed under flexion, extension, and unilateral bending and axial rotation loading conditions. Results: Under most loading conditions, the motility compensation of both cranial and caudal segments adjacent to the OLIF segment steeply aggravated with BMD reduction in S-A and BPS OLIF models. More severe motility compensation of the adjacent segment was observed in BPS models than in S-A models. Correspondingly, the surgical segment's stiffness of S-A models was apparently lower than that of BPS models (S-A models showed higher ROMs and lower stiffness in the surgical segment). Conclusion: Poor BMD aggravates the motility compensation of adjacent segments after both S-A OLIF and OLIF with BPS fixation. This variation may cause a higher risk of ASD in OLIF patients with poor BMD. S-A OLIF cannot provide instant postoperative stability; therefore, the daily motions of patients with S-A OLIF should be restricted before ideal interbody fusion to avoid surgical segment complications.

LncRNA HABON promoted liver cancer cells survival under hypoxia by inhibiting mPTP opening.

Hypoxia is an important feature of the tumor microenvironment (TME). While targeting hypoxic TME is emerging as a potential strategy for treating solid tumors including liver cancer. Recent studies have shown that hypoxia can regulate tumor adaptation to hypoxic TME through long non-coding RNA (lncRNA). In the previous study, we identify a novel hypoxia-activated lncRNA and termed it as HABON. Here, we demonstrated that knockdown of HABON caused necroptosis of tumor tissue and inhibited the subcutaneous tumor growth of SMMC-7721 cells in nude mice. Moreover, knockdown of HABON increased RIPK1 and MLKL expression as well as their phosphorylation level in SMMC-7721 and Huh7 liver cancer cells. Meanwhile, Necrostatin-1 and GSK872 could restore cell death of liver cancer cells caused by knockdown of HABON under hypoxia. The above results suggested that HABON could inhibit hypoxia-induced necroptosis of liver cancer cells. Mechanically, knockdown of HABON in liver cancer cells aggravated mitochondrial dysfunction caused by hypoxia. Furthermore, the RNA pull-down combined with mass spectrometry analysis identified HABON can interact with mitochondria-related protein VDAC1 and the RNA immunoprecipitation (RIP) analysis proved the interaction. In addition, we proved that VDAC1 mediated the mitochondrial permeability transition pore (mPTP) opening, mitochondrial dysfunction, as well as necroptosis caused by knockdown of HABON. Overall, our work demonstrates HABON can reduce hypoxia-induced necroptosis of liver cancer cells and suggests that inhibition of HABON in the hypoxic TME is a potential therapeutic strategy for treating liver cancer.

Intervertebral-spreader-assisted anterior cervical discectomy and fusion prevents postoperative axial pain by alleviating facet joint pressure.

OBJECTIVE: To evaluate the relationship of postoperative cervical axial pain with different vertebral distraction methods used during ACDF procedures in cervical spondylosis patients. METHODS: Ninety-four single-level cervical spondylotic myelopathy patients with significantly loss of intervertebral disc height who underwent ACDF surgery in our institute between January 2018 and January 2020 were enrolled. Cervical spine lateral radiographs were taken preoperatively, 3 days, 1-month, 2-month and 6-month after the surgery. The intervertebral disc height (IDH), interfacet distance (IFD), JOA (Japanese Orthopaedic Association) score, NDI (Neck Disability Index) score, nVAS (Neck Visual Analogue Scale) score and aVAS (Arm Visual Analogue Scale) score were measured. The correlation of clinical parameters and intervertebral disc height was evaluated. Then the correlation of clinical outcomes and different distraction method was evaluated. The patients were randomly divided into two groups, one uses Casper pin distractor system alone for distraction (Caspar alone group) and the other uses spreader assisted distraction method (Casper + spreader group). In biomechanical study, four cervical spine cadavers were selected for facet pressure measurements under different vertebral distraction methods, and the facet joint pressure was measured using force sensors. RESULTS: Satisfactory cervical fusion and neurological recovery were achieved in all patients. No significant correlation of IDH, IFD, JOA, NDI or aVAS with nVAS score was found. No significant difference between the change in disc height and clinical outcomes was found. However, by comparing the clinical parameters of patients in different vertebral distraction groups, we found significant changes in the early nVAS and NDI scores (P = 0.11, P = 0.48) of the Casper + spreader group (3 days postoperation), and was associated with a better nVAS score at 2 months postoperation (P < 0.05). The biomechanical study in cervical cadavers also showed significantly and continuously decreased facet joint pressure in the spreader assisted vertebral distraction group (P < 0.01). CONCLUSIONS: Spreader-assisted vertebral distraction method effectively alleviates postoperative neck pain in degenerative cervical spondylosis patients treated with ACDF. The mechanism may be related to the transient relief of facet joint pressure during the vertebral distraction procedure in ACDF.

Will the adjustment of insertional pedicle screw positions affect the risk of adjacent segment diseases biomechanically? An in-silico study.

Background: The fixation-induced biomechanical deterioration will increase the risk of adjacent segment diseases (ASD) after lumbar interbody fusion with Bilateral pedicle screw (BPS) fixation. The accurate adjustment of insertional pedicle screw positions is possible, and published studies have reported its mechanical effects. However, no studies clarified that adjusting insertional screw positions would affect the postoperative biomechanical environment and the risk of ASD. The objective of this study was to identify this issue and provide theoretical references for the optimization of insertional pedicle screw position selections. Methods: The oblique lumbar interbody fusion fixed by BPS with different insertional positions has been simulated in the L4-L5 segment of our previously constructed and validated lumbosacral model. Biomechanical indicators related to ASD have been computed and recorded under flexion, extension, bending, and axial rotation loading conditions. Results: The change of screw insertional positions has more apparent biomechanical effects on the cranial than the caudal segment. Positive collections can be observed between the reduction of the fixation length and the alleviation of motility compensation and stress concentration on facet cartilages. By contrast, no pronounced tendency of stress distribution on the intervertebral discs can be observed with the change of screw positions. Conclusions: Reducing the fixation stiffness by adjusting the insertional screw positions could alleviate the biomechanical deterioration and be an effective method to reduce the risk of ASD caused by BPS.

Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein.

PURPOSE: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. METHODS: RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-ß signaling. RESULTS: We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-ß signaling pathway due to its inhibitory role on SMAD7. CONCLUSION: ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.

Disc measurement and nucleus calibration in a smoothened lumbar model increases the accuracy and efficiency of in-silico study.

BACKGROUNDS: Finite element analysis (FEA) is an important tool during the spinal biomechanical study. Irregular surfaces in FEA models directly reconstructed based on imaging data may increase the computational burden and decrease the computational credibility. Definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard in FEA. METHODS: To increase the accuracy and efficiency of FEA, nucleus position and cross-sectional area ratio were measured from imaging data. A FEA model with smoothened surfaces was constructed using measured values. Nucleus position was calibrated by estimating the differences in the range of motion (RoM) between the FEA model and that of an in-vitro study. Then, the differences were re-estimated by comparing the RoM, the intradiscal pressure, the facet contact force, and the disc compression to validate the measured and calibrated indicators. The computational time in different models was also recorded to evaluate the efficiency. RESULTS: Computational results indicated that 99% of accuracy was attained when measured and calibrated indicators were set in the FEA model, with a model validation of greater than 90% attained under almost all of the loading conditions. Computational time decreased by around 70% in the fitted model with smoothened surfaces compared with that of the reconstructed model. CONCLUSIONS: The computational accuracy and efficiency of in-silico study can be improved in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio.

TELD with limited foraminoplasty has potential biomechanical advantages over TELD with large annuloplasty: an in-silico study.

BACKGROUND: Facetectomy, an important procedure in the in-out and out-in techniques of transforaminal endoscopic lumbar discectomy (TELD), is related to the deterioration of the postoperative biomechanical environment and poor prognosis. Facetectomy may be avoided in TELD with large annuloplasty, but iatrogenic injury of the annulus and a high grade of nucleotomy have been reported as risk factors influencing poor prognosis. These risk factors may be alleviated in TELD with limited foraminoplasty, and the grade of facetectomy in this surgery can be reduced by using an endoscopic dynamic drill. METHODS: An intact lumbo-sacral finite element (FE) model and the corresponding model with adjacent segment degeneration were constructed and validated to evaluate the risk of biomechanical deterioration and related postoperative complications of TELD with large annuloplasty and TELD with limited foraminoplasty. Changes in various biomechanical indicators were then computed to evaluate the risk of postoperative complications in the surgical segment. RESULTS: Compared with the intact FE models, the model of TELD with limited foraminoplasty demonstrated slight biomechanical deterioration, whereas the model of TELD with large annuloplasty revealed obvious biomechanical deterioration. Degenerative changes in adjacent segments magnified, rather than altered, the overall trends of biomechanical change. CONCLUSIONS: TELD with limited foraminoplasty presents potential biomechanical advantages over TELD with large annuloplasty. Iatrogenic injury of the annulus and a high grade of nucleotomy are risk factors for postoperative biomechanical deterioration and complications of the surgical segment.

Hypoxia activated long non-coding RNA HABON regulates the growth and proliferation of hepatocarcinoma cells by binding to and antagonizing HIF-1 alpha.

The adaptation of tumour cells to hypoxic microenvironment is one of the most significant characteristics of many malignant tumour diseases including hepatocarcinoma. Recently, long non-coding RNAs (lncRNAs) have been reported to play important roles in the various levels of gene regulation thus functioning in growth and survival of tumour cells. Here, new hypoxia-related lncRNAs in hepatocarcinoma cells were screened and validated by lncRNA chip-array as well as real-time RT-PCR. Among them, a hypoxia-activated lncRNA that we identified and termed Hypoxia-Activated BNIP3 Overlapping Non-coding RNA (HABON), was not only regulated by hypoxic-induced factor-1α (HIF-1α) but its expression increased significantly under hypoxia in tumour cells. We deciphered the biological characteristics of HABON including its cell localization, genomic location, as well as its full-length sequence, and proved HABON could promote growth, proliferation and clone-formation of hepatocarcinoma cells under hypoxia. Then, we revealed that HABON was transcriptionally activated by HIF-1α in hypoxic cells, furthermore, it could interact with HIF-1α and promote its protein degradation, thus affecting transcription of HIF-1α's target genes to exert its effects on cells. Besides, the elevated expression of HABON under hypoxia could promote the transcriptional activation of BNIP3 through HIF-1α, and increasing the expression level of BNIP3. This research provides a novel clue for the adaptive survival and growth mechanism of tumour under hypoxia, and gives a way to reveal the nature of tumour cells' resistance characteristics to harsh microenvironment.

Reducing the extent of facetectomy may decrease morbidity in failed back surgery syndrome.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) is widely used for the treatment of lumbar disc herniation. Facetectomy in PTED is necessary for accessing the intraspinal region and for decompressing the exiting nerve roots in patients who suffer from hypertrophy of the facet joints. However, this may increase morbidity in failed back surgery syndrome (FBSS) and has not been clearly elucidated. METHODS: A three-dimensional lumbosacral model was reconstructed and validated. And corresponding models after PTED with one-quarter and one-half excisions of the superior articular process were reconstructed. The maximum shear stress on the annulus in L5, von Mises stress of the facet cartilage, maximum principle capsular strain and deformation of the lumbosacral model were calculated using finite element methods. RESULTS: Calculated results show no significant differences in the complete model and the model with one-quarter excision of the superior articular process, but all biomechanical indexes have been deteriorated under most of the loading conditions tested in the model with one-half excision of the superior articular process. CONCLUSIONS: Less facetectomy is better because it may reduce the risk of biomechanical deterioration and consequently, that of FBSS.

Biomechanical role of osteoporosis affects the incidence of adjacent segment disease after percutaneous transforaminal endoscopic discectomy.

STUDY DESIGN: Variation in the biomechanical characteristics of intervertebral discs adjacent to the segment disc after undergoing percutaneous transforaminal endoscopic discectomy (PTED) in models with normal and abnormal bone mineral density (BMD) was estimated using the finite element method. OBJECTIVE: The study investigated the change in the incidence of adjacent segment disease (ASD) after PTED in patients without and with osteoporosis. BACKGROUNDS: PTED has been widely used for treating lumbar disc herniation (LDH); changes in BMD will affect biomechanical characteristics, possibly leading to changes in the incidence of ASD after PTED. However, this issue remains largely unclear. METHODS: A non-linear, lumbosacral finite element model was reconstructed based on imaging data and validated using compared values computed by the current model from published and well-validated, in vitro biomechanical experiment studies. Corresponding PTED models with normal and abnormal BMDs were also reconstructed. Shear and von Mises stresses on the annulus fibrosis, the von Mises stress on the endplates in L5-S1 segment discs, and the total deformation of current lumbosacral models were computed in different body positions by changing loading conditions, including flexion, extension, left and right lateral bending, and axial rotation. RESULTS: In most loading conditions, biomechanical characteristics of the lumbosacral segment discs with normal BMDs after PTED slightly increased. However, in the PTED model with osteoporosis, most of the biomechanical characteristics dramatically increased. CONCLUSION: Osteoporosis leads to the deterioration of biomechanical characteristics in the adjacent segment disc after PTED; this variation may also result in an increase in the incidence of ASD. However, further studies on the interactions between pathological changes are warranted.

Percutaneous endoscopic treatment for cervical ligamentum flavum gouty tophus: A case report.

RATIONALE: Cervical ligamentum flavum gout (CLFG) is relatively rare, and its clinical manifestations are complicated; hence, it is often confused with ligamentum flavum ossification. Gout tophi may relate to certain risk factors, such as renal insufficiency and lack of long-term effective uric acid treatment. PATIENT CONCERNS: A 73-year-old man had a half-year history of left upper extremity pain and numbness, which was aggravated 6 months ago. DIAGNOSES: Computed tomography (CT) indicated spinal stenosis at the level of C5/6. Cervical stenosis was believed to be mostly related to the ossification of ligamentum flavum. The histological examination of the material removed during the surgery revealed fibrous tissues with pools of amorphous debris having a foreign body giant cell reaction, which is typical of urate gout. INTERVENTIONS: We performed complete decompressions for this case with CLFG using posterior percutaneous endoscopic technique. OUTCOMES: The patient experienced a progressive improvement in the left upper extremity pain after the surgery, and no signs of cerebrospinal fluid leakage, infection, or other complications were experienced. LESSONS: The clinician should include spinal gout in the differential diagnosis when dealing with patients with hyperuricemia, renal insufficiency, and axial pain with or without neurologic deficits. We have applied the percutaneous endoscopic technique for the treatment of spinal gout. It performed direct decompression with minimizing trauma and instability, which could be used as an alternative choice.