The clinical effect of unilateral decompressive laminectomy plus fusion with unilateral biportal endoscopic technique for single level lumbar spinal stenosis.

PURPOSE: This study aimed to compare and analyze the effectiveness of unilateral biportal endoscopic (UBE) decompressive laminectomy plus fusion and microscope-assisted open decompressive laminectomy plus fusion. METHODS: A total of 143 patients with lumbar spinal stenosis were enrolled in this study between March 2020 and February 2021 with a minimum 2 years follow-up visit to our hospital. Sixty-five patients underwent the unilateral biportal endoscopic technique and were assigned to the UBE group, and the remaining 78 patients with microscope assistant were assigned to the Microscope group. The baseline characteristics, clinical outcomes, and radiological data were retrospectively collected and analyzed, as well as Clinical outcomes, radiological data and complications. RESULTS: There were no significant differences between the two groups in terms of baseline characteristics (P > 0.05). The UBE group was demonstrated to be significantly superior in CRP, drainage, blood loss, treatment cost and Hospital stay than the Microscope group (P < 0.05), whereas a significant longer operation time was observed (P < 0.05). The VAS-B, ODI, and JOA-L scores of the UBE group at 1 year follow-up were significantly greater than those of the Microscope group (P < 0.05). Regarding radiological data, there were no significant differences in the section area of the spinal canal and fusion grade between the two groups (P > 0.05). CONCLUSION: In view of the satisfactory clinical outcomes of patients and notable decompression at the stenosed segment, UBE is a feasible, minimally invasive technique for single level lumbar canal stenosis.

Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer.

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the most negatively correlated protein with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of ZNRF3/RNF43 stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data highlight ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptor, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.

Analysis of risk factors for axial symptoms after posterior cervical open-door laminoplasty.

BACKGROUND: Laminoplasty (LP), a procedure commonly used to treat cervical spondylotic myelopathy (CSM), often results in the development of axial symptoms (AS) postoperatively. This study aims to analyze the risk factors associated with the occurrence of AS after LP. METHODS: We collected and evaluated clinical data from 264 patients with CSM who underwent LP treatment at our institution from January 2018 to January 2022 through a single-center retrospective study. Of the patients, 153 were male and 111 were female, with an average age of 58.1 ± 6.7 years. All patients underwent C3-7 posterior laminoplasty. Based on the occurrence of postoperative axial symptoms, the patients were divided into an AS group and a non-AS group. General information, including age, gender, disease duration, Japanese Orthopaedic Association (JOA) score, postoperation early function training, and collar-wearing time, was recorded and compared between the two groups. Surgical-related data, such as operative segments, surgical time, intraoperative blood loss, intraoperative facet joint destruction, and destruction of the C7 spinous process muscle insertion, were also compared. Imaging data, including preoperative cervical curvature, cervical range of motion, preoperative encroachment rate of the anterior spinal canal, and angle of laminar opening, were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors for the development of AS after LP, and receiver operator characteristic (ROC) curves were utilized to explore the optimal preoperative parameters. RESULTS: All 264 patients successfully underwent surgery and were followed up for an average of 19.5 ± 6.8 months. At the 6-month follow-up, 117 patients were diagnosed with AS, resulting in an incidence rate of 40.2%. The multivariate logistic regression analysis identified that preoperative encroachment rate of anterior spinal canal (Pre-op ERASC), intraoperative facet joints destruction (Intra-op FJD), intraoperative open-door angle (Intra-op OA), destroy the C7 spinous process muscle insertion (Destroy C7 SPMI), postoperative loss of cervical curvature (Post-op LCC), and postoperative loss of cervical range of motion (Post-op LCROM) were independent risk factors for AS. Conversely, preoperative cervical curvature (Pre-op CC) and postoperation early function training (Post-op EFT) were protective factors against AS. According to the ROC curve, the cutoff values for preoperative anterior spinal canal occupation rate and preoperative cervical curvature were 28.5% and 16.5°, respectively. When the preoperative anterior spinal canal occupation rate was greater than 28.5% or the preoperative cervical curvature was less than 16.5°, AS was more likely to occur after surgery. CONCLUSION: High preoperative anterior spinal canal occupation rate, facet joint damage during surgery, C7 spinous process muscle stop point damage, larger angle of laminar opening, and greater postoperative cervical curvature loss and cervical range of motion loss are associated with an increased risk of developing AS after cervical laminoplasty. Conversely, a larger preoperative cervical curvature and early postoperative functional exercises can help reduce the occurrence of AS.

Risk factors analysis and risk prediction model construction of non-specific low back pain: an ambidirectional cohort study.

PURPOSE: Non-specific low back pain (NLBP) is a common clinical condition that affects approximately 60-80% of adults worldwide. However, there is currently a lack of scientific prediction and evaluation systems in clinical practice. The purpose of this study was to analyze the risk factors of NLBP and construct a risk prediction model. METHODS: We collected baseline data from 707 patients who met the inclusion criteria and were treated at the Sixth Hospital of Ningbo from December 2020 to December 2022. Logistic regression and LASSO regression were used to screen independent risk factors that influence the onset of NLBP and to construct a risk prediction model. The sensitivity and specificity of the model were evaluated by tenfold cross-validation, and internal validation was performed in the validation set. RESULTS: Age, gender, BMI, education level, marital status, exercise frequency, history of low back pain, labor intensity, working posture, exposure to vibration sources, and psychological status were found to be significantly associated with the onset of NLBP. Using these 11 predictive factors, a nomogram was constructed, and the area under the ROC curve of the training set was 0.835 (95% CI 0.756-0.914), with a sensitivity of 0.771 and a specificity of 0.800. The area under the ROC curve of the validation set was 0.762 (95% CI 0.665-0.858), with a sensitivity of 0.800 and a specificity of 0.600, indicating that the predictive value of the model for the diagnosis of NLBP was high. In addition, the calibration curve showed a high degree of consistency between the predicted and actual survival probabilities. CONCLUSION: We have developed a preliminary predictive model for NLBP and constructed a nomogram to predict the onset of NLBP. The model demonstrated good performance and may be useful for the prevention and treatment of NLBP in clinical practice.

Efficient cancer modeling through CRISPR-Cas9/HDR-based somatic precision gene editing in mice.

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either Kras or Pik3ca in both normal and hyperplastic mammary glands led to swift tumorigenesis. The resulting tumors shared some histological, transcriptome, and proteome features with tumors induced by lentivirus-mediated expression of the respective oncogenes, but they also exhibited some distinct characteristics, particularly showing less intertumor variation, thus potentially offering more consistent models for cancer studies and therapeutic development. Therefore, this technological advance fills a critical gap between the power of CRISPR technology and high-fidelity mouse models for studying human tumor evolution and preclinical drug testing.

Analysis of risk factors for contralateral symptomatic foraminal stenosis after unilateral transforaminal lumbar interbody fusion.

PURPOSE: To analyze the risk factors of contralateral symptomatic foraminal stenosis (FS) after unilateral transforaminal lumbar interbody fusion (TLIF) and to guide and standardize the operation process of unilateral TLIF to reduce the occurrence of contralateral symptomatic FS. METHODS: A retrospective study was undertaken on 487 patients with lumbar degeneration who underwent unilateral TLIF in the Department of Spinal Surgery of Ningbo Sixth Hospital between January 2017 and January 2021, comprising 269 males and 218 females, with a mean age of 57.1 years (range, 48-77 years). Cases of intraoperative improper operations, such as screw deviation, postoperative hematoma, and contralateral disc herniation, were excluded, and cases of nerve root symptoms caused by contralateral FS were analyzed. Post-surgery, 23 patients with nerve root symptoms caused by contralateral FS were categorized as group A, and 60 patients without nerve root symptoms were randomly selected as group B during the same period. The general data (gender, age, body mass index (BMI), bone mineral density (BMD), and diagnosis) and imaging parameters before and after operation (including contralateral foramen area (CFA), lumbar lordosis angle (LL), segmental lordosis angle (SL), disc height (DH), foramen height (FH), foramen width (FW), fusion cage position, and the difference between postoperative and preoperative) were compared between the two groups. Univariate analysis was performed, and multivariate analysis was undertaken through logistics analysis to determine the independent risk factors. Additionally, the clinical outcomes of the two groups were compared immediately before surgery and one year after surgery, using the visual analogue scale (VAS) score and the Japanese Orthopaedic Association (JOA) score for evaluation. RESULTS: The patients in this study were followed up for a period of 19-25 (22.8atien months. Among them, 23 cases (4.72% incidence) were diagnosed with contralaterally symptomatic FS after the surgery. Univariate analysis indicated significant differences between the two groups in CFA, SL, FW, and cage coronal position. Logistic regression analysis identified preoperative contralateral foramen area (OR = 1.176, 95% CI (1.012, 1.367)), small segmental lordosis angle (OR = 2.225, 95% CI (1.124, 4.406)), small intervertebral foramen width (OR = 2.706, 95% CI (1.028, 7.118)), and cage coronal position not crossing the midline (OR = 1.567, 95% CI (1.142, 2.149)) as independent risk factors for contralateral symptomatic FS after unilateral TLIF. However, there was no statistically significant difference in the pain VAS score between the two groups one year after the operation. In contrast, there was a significant difference in the JOA score between the two groups. CONCLUSION: The identified risk factors for contralateral symptomatic FS after TLIF include preoperative contralateral intervertebral foramen stenosis, a small segmental lordosis angle, a small intervertebral foramen width, and the coronal position of the cage not crossing the midline. For patients with these risk factors, it is recommended to carefully lock the screw rod during the recovery of lumbar lordosis and ensure that the coronal position of the fusion cage is implanted beyond the midline. If necessary, preventive decompression should also be considered. However, this study did not quantify the imaging data for each risk factor, and further research is needed to improve our understanding of the topic.

Effect of preoperative contralateral foramen stenosis on contralateral root symptoms after unilateral transforaminal lumbar interbody fusion: a ambispective cohort study.

PURPOSE: To evaluate the correlation between the degree of preoperative contralateral foraminal stenosis(CFS) and the incidence of contralateral root symptoms after unilateral transforaminal lumbar interbody fusion(TLIF) and to evaluate the appropriate candidate of preventive decompression according to the degree of preoperative contralateral foraminal stenosis. METHODS: An ambispective cohort study was conducted to investigate the incidence of contralateral root symptoms after unilateral transforaminal lumbar interbody fusion (TLIF) and the effectiveness of preventive decompression. A total of 411 patients were included in the study, all of whom met the inclusion and exclusion criteria and underwent surgery at the Department of Spinal Surgery, Ningbo Sixth Hospital, between January 2017 and February 2021. The study was divided into two groups: retrospective cohort study A and prospective cohort study B. The 187 patients included in study A from January 2017 to January 2019 did not receive preventive decompression. They were divided into four groups based on the degree of preoperative contralateral intervertebral foramen stenosis: no stenosis group A1, mild stenosis group A2, moderate stenosis group A3, and severe stenosis group A4. A Spearman rank correlation analysis was used to evaluate the correlation between the preoperative contralateral foramen stenosis degree and the incidence of contralateral root symptoms after unilateral TLIF. From February 2019 to February 2021, 224 patients were included in the prospective cohort group B. The decision to perform preventive decompression during the operation was based on the degree of preoperative contralateral foramen stenosis. Severe intervertebral foramen stenosis was treated with preventive decompression as group B1, while the rest were not treated with preventive decompression as group B2. The baseline data, surgical-related indicators, the incidence of contralateral root symptoms, clinical efficacy, imaging results, and other complications were compared between group A4 and group B1. RESULTS: All 411 patients completed the operation and were followed up for an average of 13.5 ± 2.8 months. In the retrospective study, there was no significant difference in baseline data among the four groups (P > 0.05). The incidence of postoperative contralateral root symptoms increased gradually, and a weak positive correlation was found between the degree of preoperative intervertebral foramen stenosis and the incidence of postoperative root symptoms (rs = 0.304, P < 0.001). In the prospective study, there was no significant difference in baseline data between the two groups. The operation time and blood loss in group A4 were less than those in group B1 (P < 0.05). The incidence of contralateral root symptoms in group A4 was higher than that in group B1 (P = 0.003). However, there was no significant difference in leg VAS score and ODI index between the two groups at 3 months after the operation (P > 0.05). There was no significant difference in cage position, intervertebral fusion rate, and lumbar stability between the two groups (P > 0.05). No incisional infection occurred after the operation. No pedicle screw loosening, displacement, fracture, or interbody fusion cage displacement occurred during follow-up. CONCLUSION: This study found a weak positive correlation between the degree of preoperative contralateral foramen stenosis and the incidence of contralateral root symptoms after unilateral TLIF. Intraoperative preventive decompression of the contralateral side may prolong the operation time and increase intraoperative blood loss to some extent. However, when the contralateral intervertebral foramen stenosis reaches the severe level, it is recommended to perform preventive decompression during the operation. This approach can reduce the incidence of postoperative contralateral root symptoms while ensuring clinical efficacy.

Short-term PI3K Inhibition Prevents Breast Cancer in Preclinical Models.

Antiestrogen medication is the only chemoprevention currently available for women at a high risk of developing breast cancer; however, antiestrogen therapy requires years to achieve efficacy and has adverse side effects. Therefore, it is important to develop an efficacious chemoprevention strategy that requires only a short course of treatment. PIK3CA is commonly activated in breast atypical hyperplasia, the known precancerous precursor of breast cancer. Targeting PI3K signaling in these precancerous lesions may offer a new strategy for chemoprevention. Here, we first established a mouse model that mimics the progression from precancerous lesions to breast cancer. Next, we demonstrated that a short-course prophylactic treatment with the clinically approved PI3K inhibitor alpelisib slowed early lesion expansion and prevented cancer formation in this model. Furthermore, we showed that alpelisib suppressed ex vivo expansion of patient-derived atypical hyperplasia. Together, these data indicate that the progression of precancerous breast lesions heavily depends on the PI3K signaling, and that prophylactic targeting of PI3K activity can prevent breast cancer. PREVENTION RELEVANCE: PI3K protein is abnormally high in breast precancerous lesions. This preclinical study demonstrates that the FDA-approved anti-PI3K inhibitor alpelisib can prevent breast cancer and thus warrant future clinical trials in high-risk women.

STAT5 confers lactogenic properties in breast tumorigenesis and restricts metastatic potential.

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in vitro. Furthermore, we demonstrated that STAT5aca overexpression in human breast cancer cells lowered their metastatic burden in xenografted mice. Moreover, RPPA, Western blotting, and studies of ChIPseq data identified several EMT drivers regulated by STAT5. In addition, bioinformatic studies detected a correlation between STAT5 activity and better prognosis of breast cancer patients. Together, we conclude that STAT5 activation during mammary tumorigenesis specifies a tumor phenotype of lactogenic differentiation, suppresses EMT, and diminishes potential for subsequent metastasis.

Posterior temporary fixation of C1-C2 screw-rod system for unstable C1 burst fracture.

Whether an unstable C1 burst fracture should be treated surgically or conservatively is controversial. The purpose of this study is to evaluate the effectiveness and motion-preserving function of temporary fixation of C1-C2 screw-rod system for the reduction and fixation of unstable C1 burst fracture. We retrospectively reviewed 10 patients who were treated with posterior C1-C2 temporary fixation without fusion. We assessed age at surgery, gender, pre- and postoperative visual analog scale (VAS), Neck Disability Index (NDI), atlanto-dens interval (ADI), lateral mass distance (LMD), and rotation function of C1-C2 complex. Six males and 4 females were included in our study. The average follow-up duration was 14.1 ± 1.37 months. The left-to-right ROMs of C1-C2 rotation was 9.6° ± 1.42°. The preoperative cervical VAS was 8.30 ± 0.48; the postoperative cervical VAS of C1-C2 fusion was 2.90 ± 0.57. The preoperative VAS for removal was 2.0 ± 0.00, and the postoperative VAS for removal was 2.3 ± 0.48. The preoperative cervical NDI was 81.40% ± 2.07%, the postoperative cervical NDI of C1-C2 fusion was 18.10% ± 1.52%. The preoperative NDI for removal was 15.9% ± 1.20%. The postoperative NDI for removal was 14.5% ± 1.08%. The preoperative ADI was 4.43 ± 0.34 mm, and postoperative ADI was 1.94 ± 0.72 mm. The preoperative LMD was 6.36 ± 0.58 mm, and postoperative LMD was 1.64 ± 0.31 mm. Posterior temporary C1-C2 fixation can achieve a good fusion and satisfied reduction of C1 fracture, relieve the pain, improve the cervical function outcome, but may reduce the rotational range of motion of C1-C2. Posterior C1-C2 temporary fixation without fusion was not suitable for C1 burst fracture. We recommend permanent C1-C2 fixation and fusion for C1 burst fracture if surgery is necessary.

Targeting the Pro-survival Protein BCL-2 to Prevent Breast Cancer.

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone receptor. Venetoclax is a BH3 mimetic that blocks the anti-apoptotic protein BCL-2 and has efficacy in treating breast cancer. We found that venetoclax treatment of atypia-bearing mice delayed the progression to tumors, improved overall survival, and reduced pulmonary metastasis. Therefore, prophylactic treatment to inhibit the pro-survival protein BCL-2 may provide an alternative to the currently available regimens in breast cancer prevention. PREVENTION RELEVANCE: This study demonstrates that prophylactic treatment with the BCL2-specific antagonist venetoclax prevents breast cancer initiated by a mutated and activated PIK3CA, the most common breast oncogene.

Reliability and repeatability of a modified thoracolumbar spine injury classification scoring system.

Purpose: On the basis of the Thoracolumbar Injury Classification and Severity Score (TLICS), an modified TLICS classification system was presented, its reliability and repeatability were assessed, and the factors influencing classification consistency were examined. Methods: Five spinal surgeons were chosen at random. The clinical data of 120 patients with thoracolumbar fractures admitted to the Department of Spine Surgery, Ningbo Sixth Hospital from December 2019 to June 2021 were categorized using the modified TLICS system. After 6 weeks, disrupt the order of data again. Using unweighted Cohen's kappa coefficients, the consistency of the modified TLICS system was assessed in five aspects: neurofunctional status, disc injury status, fracture morphology, posterior ligament complex (PLC) integrity, and treatment plan. Results: In terms of reliability, the average kappa values for the subclasses of the modified TLICS system (neurofunctional status and disc injury status) were 0.920 and 0.815, respectively, reaching the category of complete confidence. Fracture morphology and treatment plan had average kappa values of 0.670 and 0.660, respectively, which were basically reliable. The average kappa value of PLC integrity was 0.453, which belonged to the category of moderate confidence. The average kappa coefficients of each subcategory (neurological status, disc injury status) had excellent consistency, and the kappa values were 0.936 and 0.879, respectively, which belonged to the completely credible category. The kappa values of fracture morphology and treatment plan repeatability were 0.772 and 0.749, respectively, reaching the basic credibility category. PLC integrity repeatability kappa value is low, 0.561, to moderate credibility category. Conclusion: The modified TLICS system is intuitive and straightforward to understand. The examination of thoracolumbar fracture injuries is more exhaustive and precise, with excellent reliability and repeatability. The examination of neurological status and disc injury status is quite reliable and consistent. The consistency of fracture morphology is slightly poor, which is basically credible; the PLC integrity consistency is poor, reaching a reliability level of moderate, which may be associated with the subjectivity of clinical evaluation of PLC.

A Wnt-Independent LGR4-EGFR Signaling Axis in Cancer Metastasis.

Leucine-rich repeat-containing G protein-coupled receptors 4, 5, and 6 (LGR4/5/6) play critical roles in development and cancer. The widely accepted mechanism is that these proteins, together with their R-spondin ligands, stabilize Wnt receptors, thus potentiating Wnt signaling. Here we show that LGR4 enhanced breast cancer cell metastasis even when Wnt signaling was deactivated pharmacologically or genetically. Furthermore, LGR4 mutants that cannot potentiate Wnt signaling nevertheless promoted breast cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Multiomic screening identified EGFR as a crucial mediator of LGR4 activity in cancer progression. Mechanistically, LGR4 interacted with EGFR and blocked EGFR ubiquitination and degradation, resulting in persistent EGFR activation. Together, these data uncover a Wnt-independent LGR4-EGFR signaling axis with broad implications for cancer progression and targeted therapy. SIGNIFICANCE: This work demonstrates a Wnt-independent mechanism by which LGR4 promotes cancer metastasis.See related commentary by Stevens and Williams, p. 4397.

The bone microenvironment invigorates metastatic seeds for further dissemination.

Metastasis has been considered as the terminal step of tumor progression. However, recent genomic studies suggest that many metastases are initiated by further spread of other metastases. Nevertheless, the corresponding pre-clinical models are lacking, and underlying mechanisms are elusive. Using several approaches, including parabiosis and an evolving barcode system, we demonstrated that the bone microenvironment facilitates breast and prostate cancer cells to further metastasize and establish multi-organ secondary metastases. We uncovered that this metastasis-promoting effect is driven by epigenetic reprogramming that confers stem cell-like properties on cancer cells disseminated from bone lesions. Furthermore, we discovered that enhanced EZH2 activity mediates the increased stemness and metastasis capacity. The same findings also apply to single cell-derived populations, indicating mechanisms distinct from clonal selection. Taken together, our work revealed an unappreciated role of the bone microenvironment in metastasis evolution and elucidated an epigenomic reprogramming process driving terminal-stage, multi-organ metastases.

Revision surgery after cement augmentation for osteoporotic vertebral fracture.

INTRODUCTION: Cement augmentation has been proven to be a safe procedure for the treatment of osteoporotic vertebral fracture, and the overall result is encouraging. However, failures caused by different complications are not uncommon, and a few patients even need revision surgery. This retrospective study aimed to investigate the primary causes of revision surgery after cement augmentation for osteoporotic vertebral fracture and how to prevent them, and the second objective was to evaluate the clinical results of revision surgery. HYPOTHESIS: The main hypothesis is that infection and neurological dysfunction are the prime causes of revision surgery after cement augmentation for osteoporotic vertebral fracture, and the second hypothesis is that revision surgery is effective to improve the quality of daily life. MATERIALS AND METHODS: Twenty-one patients who underwent unplanned revision surgery after cement augmentation were retrospectively analyzed. The initial radiographic and medical records were reviewed to re-evaluate whether the initial diagnosis and surgical procedure were correct and suitable. The primary causes of revision surgery and the details were recorded. The visual analog scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the efficacy of the revision surgery, and patients with neurological dysfunction were evaluated with the American Spinal Injury Association (ASIA). RESULTS: A total of 47.6% (10/21) of patients were misdiagnosed initially or had an incorrect indication for cement augmentation surgery, including 3 pre-existing spondylitis cases that were misdiagnosed as osteoporotic vertebral fracture and 7 cases of three column fractures that were treated with cement augmentation. The primary causes and details of the revision surgeries were as follows: 7 patients with infection underwent anterior and/or posterior debridement and fixation; 9 patients with progressive kyphosis underwent posterior osteotomy and fixation; and 5 patients with neurological dysfunction underwent posterior decompression and fixation. The mean follow-up time was 30.6±8.7 months, the VAS score decreased from 7.3±1.1 preoperatively to 2.3±0.3 (p<0.05) at the last follow-up, the ODI decreased from 61.1%±16.3% preoperatively to 20.6%±6.2% (p<0.05) at the last follow-up, and 5 patients with neurological dysfunction improved by at least one grade. CONCLUSION: Infection, progressive kyphosis and neurological dysfunction are the primary causes of revision surgery after cement augmentation for osteoporotic vertebral fracture. Avoiding misdiagnosis and ensuring suitable indications might be the key points to decreasing unplanned revision surgery for cement augmentation for osteoporotic vertebral fracture. The quality of daily life and neurological function can be improved through revision surgery.

Posterior short segment fixation including the fractured vertebra combined with kyphoplasty for unstable thoracolumbar osteoporotic burst fracture.

BACKGROUND: Various studies have described the efficacy and safety of the treatment for unstable thoracolumbar osteoporotic burst fracture, however, there is still no consensus on the optimal treatment regimen. The aim of this study was to evaluate the clinical and radiographic results of posterior short segment fixation including the fractured vertebra (PSFFV) combined with kyphoplasty (KP) for unstable thoracolumbar osteoporotic burst fracture. METHODS: Forty-three patients with unstable thoracolumbar osteoporotic burst fracture underwent PSFFV combined with KP from January 2015 to December 2017 were analyzed retrospectively. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) was used to evaluate the clinical outcome, radiological parametres including local kyphotic Cobb angle, percentage of the anterior, middle and posterior height of the fractured vertebra were measured and compared pre-operation, post-operation and at final follow-up. RESULTS: All patients underwent surgery successfully and with an average follow-up of 19.2 ± 6.7 months (rang 15-32). The VAS decreased from 7.1 ± 2.3 pre-operation to 1.6 ± 0.4 at the final follow-up (p < 0.05). The ODI decreased from 83.1 ± 10.5 pre-operation to 19.2 ± 7.3 (P < 0.05) at the final follow-up. The correction of local kyphotic angle was 16.9° ± 5.3° (p < 0.05), and the loss of correction was 3.3° ± 2.6° (p > 0.05), the correction of anterior vertebral height was 30.8% ± 8.6% (p < 0.05), and the loss of correction was 4.5% ± 3.9% (p > 0.05), the correction of middle vertebral height was 26.4% ± 5.8% (p < 0.05), and the loss of correction was 2.0% ± 1.6% (p > 0.05), the correction of posterior vertebral height was 9.4% ± 6.9% (p < 0.05), and the loss of correction was 1.6% ± 1.3% (p > 0.05). Two cases of screw pullout and 8 cases of cement leakage were observed, but without clinical consequence. CONCLUSIONS: PSFFV combined with KP is a reliable and safe procedure with satisfactory clinical and radiological results for the treatment of unstable thoracolumbar osteoporotic burst fracture.

[Comparison of the effects of injured vertebra pedicle fixation combined with vertebroplasty and vertebra pedicle screw fixation combined with vertebroplasty in the treatment of osteoporotic thoracolumbar burst fractures].

OBJECTIVE: To assess the curative effects of injured vertebra pedicle fixation combined with vertebroplasty and short-segment pedicle screw fixation combined with vertebroplasty in treatment of osteoporotic thoracolumbar burst fractures. METHODS: Seventy patients with osteoporotic thoracolumbar burst fractures who met the inclusion criteria were collected in the study from January 2015 to December 2017. Among them, 35 patients were treated with injured vertebra pedicle fixation combined with vertebroplasty (group A), including 20 males and 15 females, aged from 55 to 74 years with an average of (64.03± 7.82) years. Twenty-six cases were type A3 and 9 cases were type A4 according to the AO typing;another 35 patients were treated with short segment pedicle screw fixation combined with vertebroplasty (group B), including 18 males and 17 females, aged from 54 to 72 years with an average of (62.78±6.40) years. Twenty-eight cases were type A3 and 7 cases were type A4 according to AO typing. Operation length, intraoperative bleeding volume, complication, imaging parameters and clinical effects were compared between the two groups. RESULTS: All the patients were followed up for at least 12 months. There were no significant differences in gender, age, injury site, preoperative VAS, Cobb angle, and injured vertebral height before surgery. There were no significant differences in operation length, intraoperative bleeding volume between two groups. In terms of VAS scores before surgery, 1 week after surgery, and at the final follow up, group A was 5.5 ±2.5, 1.8 ±0.8, 0.9 ±0.4, group B was 5.4 ± 2.3, 1.7±0.6, 1.2±1.8, respectively;injured vertebral height was (40.4±8.8)%, (92.0±4.9)%, (87.1±3.8)% in group A, and (41.2±6.6)%, (93.2±4.6)%, (80.0±4.3)% in group B;Cobb angle was (18.4±6.9) °, (2.8±2.2) °, (4.2±2.6) ° in group A, and (16.8±7.2) °, (2.7±2.5) °, (6.0±2.4) ° in group B. There were significant differences in the 3 parameters above before the operation and at the final follow up in all groups (P<0.05). There were significant differences in the Cobb angle and injured vertebral height between 1 week after operation and at the final follow up (P<0.05). At the final follow up, injured vertebral height in group A was obviously better than that in group B (P<0.05). Internal fixation failure occurred in 2 cases from the group A, and occurred in 4 cases from the group B. There were no neurological complications in both groups. CONCLUSION: For osteoporotic thoracolumbar vertebral burst fractures, injured vertebra pedicle fixation combined with vertebroplasty and vertebra pedicle screw fixation combined with vertebroplasty can achieve good clinical effects. However, injured vertebra pedicle fixation combined with vertebroplasty is better at maintaining postoperative vertebral height and sagittal arrangement, and reducing internal fixation related complications. The treatment strategy is worthy of application and promotion.

The role of surface sulfation in mediating the acidity and oxidation ability of nickel modified ceria catalyst for the catalytic elimination of chlorinated organics.

Surface sulfation has shown to be an effective way in modifying the acidity and oxygen mobility of metal oxide catalysts. Both of the properties were crucial in the catalytic elimination of chlorinated organics from industrial source of emission. Herein, sulfation of a dry-mixed NiO/CeO2 catalyst was conducted. The catalyst was subsequently utilized for eliminating chlorobenzene (CB) under a simulated realistic condition. A range of analytical techniques, including XRD, XPS, in situ DRIFT and NH3-DRIFT were employed to elucidate the sulfation effect on the physiochemical property and reaction activity of NiO/CeO2. Enhanced Lewis acidity and enriched surface oxygen vacancies originating from the interaction of sulfates and metal ions were observed, which led to improved conversion efficiency and COx (CO + CO2) selectivity in CB oxidation. In particular, qualitative analyses of reaction byproducts in the off-gas indicated that sulfation modification did not cause severe electrophilic chlorination of NiO/CeO2, and resulted in limited production of polychlorinated byproducts and less secondary pollution of the catalyst.

eIF2α-CHOP-BCl-2/JNK and IRE1α-XBP1/JNK signaling promote apoptosis and inflammation and support the proliferation of Newcastle disease virus.

Newcastle disease virus (NDV) causes severe infectious disease in poultry and selectively kills tumor cells, by inducing apoptosis and cytokines secretion. In this report, we study the mechanisms underlying NDV-induced apoptosis by investigating the unfolded protein response (UPR). We found that NDV infection activated all three branches of the UPR signaling (PERK-eIF2α, ATF6, and IRE1α) and triggered apoptosis, in avian cells (DF-1 and CEF) and in various human cancer cell types (HeLa, Cal27, HN13, A549, H1299, Huh7, and HepG2). Interestingly, the suppression of either apoptosis or UPR led to impaired NDV proliferation. Meanwhile, the inhibition of UPR by 4-PBA protected cells from NDV-induced apoptosis. Further study revealed that activation of PERK-eIF2α induced the expression of transcription factor CHOP, which subsequently promoted apoptosis by downregulating BCL-2/MCL-1, promoting JNK signaling and suppressing AKT signaling. In parallel, IRE1α mediated the splicing of XBP1 mRNA and resulted in the translation and nuclear translocation of XBP1s, thereby promoting the transcription of ER chaperones and components of ER-associated degradation (ERAD). Furthermore, IRE1α promoted apoptosis and cytokines secretion via the activation of JNK signaling. Knock down and overexpression studies showed that CHOP, IRE1α, XBP1, and JNK supported efficient virus proliferation. Our study demonstrates that the induction of eIF2α-CHOP-BCL-2/JNK and IRE1α-XBP1/JNK signaling cascades promote apoptosis and cytokines secretion, and these signaling cascades support NDV proliferation.