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.

Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history.

BACKGROUND: After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all. RESULTS: We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV). CONCLUSIONS: We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies.

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Density Functional Theory and Machine Learning-Based Quantitative Structure-Activity Relationship Models Enabling Prediction of Contaminant Degradation Performance with Heterogeneous Peroxymonosulfate Treatments.

Heterogeneous peroxymonosulfate (PMS) treatment is recognized as an effective advanced oxidation process (AOP) for the treatment of organic contaminants. Quantitative structure-activity relationship (QSAR) models have been applied to predict the oxidation reaction rates of contaminants in homogeneous PMS treatment systems but are seldom applied in heterogeneous treatment systems. Herein, we established QSAR models updated with density functional theory (DFT) and machine learning approaches to predict the degradation performance for a series of contaminants in heterogeneous PMS systems. We imported the characteristics of organic molecules calculated using constrained DFT as input descriptors and predicted the apparent degradation rate constants of contaminants as the output. The genetic algorithm and deep neural networks were used to improve the predictive accuracy. The qualitative and quantitative results from the QSAR model for the degradation of contaminants can be used to select the most appropriate treatment system. A strategy for selection of the optimum catalyst for PMS treatment of specific contaminants was also established according to the QSAR models. This work not only increases our understanding of contaminant degradation in PMS treatment systems but also highlights a novel QSAR model to predict the degradation performance in complicated heterogeneous AOPs.

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.

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.

Advances in Plant Epigenome Editing Research and Its Application in Plants.

Plant epistatic regulation is the DNA methylation, non-coding RNA regulation, and histone modification of gene sequences without altering the genome sequence, thus regulating gene expression patterns and the growth process of plants to produce heritable changes. Epistatic regulation in plants can regulate plant responses to different environmental stresses, regulate fruit growth and development, etc. Genome editing can effectively improve plant genetic efficiency by targeting the design and efficient editing of genome-specific loci with specific nucleases, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9). As research progresses, the CRISPR/Cas9 system has been widely used in crop breeding, gene expression, and epistatic modification due to its high editing efficiency and rapid translation of results. In this review, we summarize the recent progress of CRISPR/Cas9 in epigenome editing and look forward to the future development direction of this system in plant epigenetic modification to provide a reference for the application of CRISPR/Cas9 in genome editing.

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.

Identification of Tiny Surface Cracks in a Rugged Weld by Signal Gradient Algorithm using the ACFM Technique.

It is still a big challenge to identify tiny surface cracks in a rugged weld due to the lift-off variations using the nondestructive testing (NDT) method. In this paper, the signal gradient algorithm is presented to identify the tiny surface crack in the rugged weld using the alternating current field measurement (ACFM) technique. The ACFM simulation model and testing system was set up to obtain the insensitive signal to the lift-off variations. The signal gradient algorithm was presented to process the insensitive signal for the identification of the tiny surface crack in the rugged weld. The results show that the Bz signal is the insensitive signal to lift-off variations caused by the rugged weld. The signal to noise ratio (SNR) of the crack identification signal was greatly improved by the signal gradient algorithm, and a tiny surface crack can be identified effectively in the weld and the heat affected zone (HAZ).

A randomized controlled trial: comparing extracorporeal shock wave therapy versus local corticosteroid injection for the treatment of carpal tunnel syndrome.

PURPOSE: Extracorporeal shock wave therapy (ESWT) has been reported as a new therapy for carpal tunnel syndrome (CTS). However, few studies have compared ESWT with the local corticosteroid injection (LCI). METHODS: In this study, a randomized controlled trial comparing 30 patients with ESWT and 25 patients treated with LCI was conducted. The clinical outcomes were obtained with tests including the visual analog scale (VAS) for pain and paresthesia, the Boston Carpal Tunnel Questionnaire (BQ), and a nerve conduction study, before the study started and at three, nine, and 12 weeks after the start of the treatment. RESULTS: Significantly greater improvement in the VAS and BQ scores was noted for the ESWT group than for the LCI group (P < 0.05). For the nerve conduction study, there was a significant improvement in the median nerve sensory nerve action potential distal latency at the nine and 12-week follow-ups for the ESWT group. CONCLUSIONS: ESWT is a useful noninvasive short-term treatment for mild to moderate carpal tunnel syndrome and elicits a better recovery than LCI does, but more research is needed to test the clinical outcomes of ESWT.

Synergistic Elimination of NOx and Chloroaromatics on a Commercial V2O5-WO3/TiO2 Catalyst: Byproduct Analyses and the SO2 Effect.

The synergistic control of multipollutants is the frontier of environmental catalysis. This research is in the infancy stage, and many uncertainties still remain. Herein, we investigated the reaction characteristics of synergistic elimination of NOx and chloroaromatics on a commercial V2O5-WO3/TiO2 catalyst. The reaction byproducts were qualitatively and quantitatively analyzed, and their origins were clarified. In particular, the origins of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) from the synergistic reaction with or without SO2 were first explored; this is crucial for assessing the environmental risk by applying such a synergistic system. Experimental results indicate that during the synergistic reaction, the V2O5-WO3/TiO2 catalyst was deactivated at 200 and 250 °C, whereas the 300 °C was sufficient to durably convert the NO and chlorobenzene at the turnover frequency (TOF) of 7.23 × 10-4 and 1.32 × 10-4 s-1, respectively. A range of aromatics, alkenes, and alkanes, particularly their chlorinated congeners, were observed in the off-gases and on the catalyst surface, where those of 3-chlorobenzonitrile, 4-chloro-2-nitrophenol, and inorganic CS2 were first discovered. In the time-on-stream test at 250 °C, the PCDD/Fs collected from the off-gases was measured at 0.0514 ng I-TEQ Nm-3, but the most toxic dioxins congener, 2,3,7,8-TCDD, was not observed. The alkalinity of selective catalytic reduction reaction likely facilitated the chlorophenol formation, which eventually promoted PCDD/F generation. The SO2 was found to benefit polychlorinated byproduct generation, but the addition of which distinctly inhibited PCDD/F formation.

Catalytic Oxidation of Chlorinated Organics over Lanthanide Perovskites: Effects of Phosphoric Acid Etching and Water Vapor on Chlorine Desorption Behavior.

In this article, the underlying effect of phosphoric acid etching and additional water vapor on chlorine desorption behavior over a model catalyst La3Mn2O7 was explored. Acid treatment led to the formation of LaPO4 and enhanced the mobility of lattice oxygen of La3Mn2O7 evidenced by a range of characterization (i.e., X-ray diffraction, temperature-programmed analyses, NH3-IR, etc.). The former introduced thermally stable Brönsted acidic sites that enhanced dichloromethane (DCM) hydrolysis while the latter facilitated desorption of accumulated chlorine at elevated temperatures. The acid-modified catalyst displayed a superior catalytic activity in DCM oxidation compared to the untreated sample, which was ascribed to the abundance of proton donors and Mn(IV) species. The addition of water vapor to the reaction favored the formation and desorption of HCl and avoided surface chlorination at low temperatures. This resulted in a further reduction in reaction temperature under humid conditions ( T90 of 380 °C for the modified catalyst). These results provide an in-depth interpretation of chlorine desorption behavior for DCM oxidation, which should aid the future design of industrial catalysts for the durable catalytic combustion of chlorinated organics.

Missed manubriosternal dislocation in patient with thoracolumbar fracture, a case report.

BACKGROUND: Spine fractures combined with sternal injury are most commonly occur in the thoracic region. Lower cervical and thoracolumbar injuries have also been reported, especially for the patients with manubriosternal dislocation. The type of spine injury is easily recognized in initial presentation, but we may miss the sternal fracture and manubriosternal dislocation. CASE PRESENTATION: A 23-year-old male patient complained with chest, right ankle, and lumbar pain after a fall at ground level, with diagnosis of right distal tibial fracture, sternal fracture, calcaneus fracture, and L2 vertebral fracture. However, neurologically he was completely normal. He underwent the operation for his lower extremity and spine, but we missed his manubriosternal dislocation after discharged. After one month, he came to the clinic with complained of chest pain, the imaging exams showed anterior dislocation of manubriosternal joint. We chose conservative treatment for manubriosternal dislocation. He was followed up at monthly intervals and radiographs along with computerized tomography showed satisfactory in fracture healing of lumber and the sternal fracture. However, the manubriosternal dislocation was malunioned. The patient had appearance deformity of the manubriosternal joint. CONCLUSION: This case supports the concept of the existence and clinical relevance of the thoracic cage theory, the thoracolumbar vertebrae should also be included in the thoracic cage theory.

Surgical treatment of compressive spinal hemangioma : A case series of three patients and literature review.

PURPOSE: In this article we describe the treatment of compressive vertebral hemangioma. METHODS: Our case series comprised three patients with aggressive hemangioma. We performed a combination of posterior decompression and vertebroplasty for the two patients with a sacral hemangioma and a thoracic hemangioma, and en bloc resection for the third patient, who also had a thoracic lesion. RESULTS: Surgical intervention is indicated in cases of rapidly progressive tumors or severe myelopathy. All three patients had good clinical results. The follow-up period ranged from 8 to 56 months. The mean blood loss was around 700 ml, and mean surgical time was 2.1 h. Blood loss for the en bloc procedure was around 1,200 ml, and surgical time was 2.3 h. CONCLUSION: A combination of posterior decompression, vertebroplasty, and posterior fixation for aggressive hemangioma can reduce blood loss during surgery. For patients with hemangioma and with incomplete paralysis, total en bloc spondylectomy should be considered. Adjuvant radiotherapy can reduce the recurrence of cavernous vertebral hemangiomas.

An RCT study on the feasibility of anterior transpedicular screw fixation in the cervicothoracic junction.

STUDY DESIGN: We evaluated the trajectory and the entry points of anterior transpedicular screws (ATPS) in the cervicothoracic junction (CTJ). OBJECTIVE: This study aimed at investigating the feasibility of ATPS fixation in the CTJ. Application of an ATPS in the lower cervical spine has been reported; however, there were no reports exploring the feasibility of anterior transpedicular screw fixation in the CTJ. METHODS: CT scans were performed in 50 cases and multiplanar reformation was used to measure the related parameters on pedicle axis view at C6-T2. Transverse pedicle angle, outer pedicle width, pedicle axis length, distance transverse intersection point (DtIP), sagittal pedicle angle, anterior vertebral body height, outer pedicle height, and distance sagittal intersection point (DsIP) were measured. The prozone of CTJ was divided into three different regions, which were named as the "manubrium region", the region "above" and "below" the manubrium. The distribution of the trajectory of sagittal pedicle axes was recorded in the three regions and the related data were statistically analyzed. RESULTS: There was no statistical difference in gender (P > 0.05). The transverse pedicle angle decreased from C6 (46.77° ± 2.72°) to T2 (20.62° ± 5.04°). DtIP increased from C6 to T2. DsIP was an average of 7.17 mm. The sagittal pedicle axis lines of the C6 and C7 were located in the region above the manubrium. T1 was mainly in the manubrium region followed by the region above the manubrium. T2 was mainly located in the manubrium region followed by the region below the manubrium. CONCLUSION: Implantation of ATPS at C6, C7, and some T1 is feasible through the low anterior cervical approach, while it is almost impossible to approach T2 that way.

Anterior transpedicular screws in conjunction with plate fixation and fusion for the treatment of subaxial cervical spine diseases.

OBJECTIVE: This study aimed at exploring the clinical application of anterior transpedicular screw (ATPS) and plate in the reconstruction of subaxial cervical spine. METHODS: 8 cases were reconstructed by ATPS and plate in the subaxial cervical spine from Jan 2009 to Dec 2011. X-rays and computed tomography images were collected to evaluate the position of ATPS. Magnetic resonance imaging was also included to evaluate the result of decompression, the existence of epidural hematoma and the morphology of the cervical spinal cord. Japanese Orthopaedic Association scores were observed before and after operation as a functional estimation. RESULTS: All of the eight cases were followed up from 3 to 36 months with the average of 15.5 months. A total of 16 ATPS were implanted in the subaxial cervical spine in the eight patients. All the screws were inserted smoothly. Bone fusion was found in all the subjects 4.5 months after operation on average. No loosening or breakage of the internal fixation was observed in our study. Hoarseness was observed in one case due to distraction injury of the recurrent laryngeal nerve, which disappeared after 3 weeks' conservative treatment. Dysphagia was complained by two patients after surgery, which was alleviated 3 months later. There were four screws deviating less than 1 mm (Grade 1), two medially and two laterally. All the anterior compressions were removed completely in this group. Only a small amount of epidural hematoma was found in four cases on MRI images before discharge. The average JOA scores were significantly improved from 5.6 ± 1.4 before surgery to 14.5 ± 0.8 at discharge (P < 0.01), which decreased to 13.2 ± 1.2 at 3 months after operation, but improved again to 15.2 ± 0.8 at 1 year after operation. CONCLUSION: Although there are some complications, ATPS with plate is an effective and safe technique for anterior reconstruction in the subaxial cervical spine. Only those spine centers with sufficient experience in complex cervical spine reconstruction surgery can conduct this technique according to strict indications.

[Three-dimensional finite-element study on anterior transpedicular screw fixation system of the subaxial cervical spine].

OBJECTIVE: To evaluate the biomechanical effects of the anterior cervical transpedicular-screw system (ACTPS), compared to the anterior cervical screw plate system (ACLP), in the subaxial cervical spine after 2-level corpectomy. METHODS: A verified intact finite element subaxial cervical (C3-C7) model was established and analyzed by Mimics 10.0, Rapidform XOR3, Hypermesh 10.0, CATIA5V19, ANSYS 14.0 softwares based on the CT data (C1-T1) was collected from a 28 years old male volunteer. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3, which made the model movement in flexion extension, lateral bending, rotating direction, respectively. Then, recorded the range of motion, and compared the results with the in vitro biomechanical experimental data to verify the effectiveness of the model. The ACTPS model and the ACLP model were analyzed using the finite element method. The range of motion at the operation segments (C4-C7), the range of motion at the adjacent segment (C3-C4) and stress distribution under flexion, extension, lateral bending, and axial rotation were calculated, and compared the range of motion with intact model. RESULTS: There were 85,832 elements and 23,612 nodes in the intact model of subaxial cervical spine (C3-C7) in this experiment,and the range of motion of intact model validated with the reported cadaveric experimental data. In ACTPS group the stress was been well-distributed, but the stress concentrated on the interface between screw and the titanium plate in ACLP group. There were obvious differences of the maximum stress value between the two groups. The range of motion of fixed segments in ACTPS group was smaller than ACLP group, however adjacent segment range of motion showed no significant difference. Compared with the intact group, the range of motion in flexion extension, lateral flexion, rotation direction was decreased respectively about 25°, 20° and 8°, the range of motion at adjacent segment (C3-C4) was correspondingly compensated about 0.3°, 3° and 0.1°. CONCLUSIONS: ACTPS is better than ACLP in terms of biomechanical properties. It offers rigid stability, and may be more suitable for reconstruction stability of 2-level and more than 2 levels corpectomy in the subaxial cervical spine. Meanwhile, the risk of fracture of ACTPS system is lower than that of the ACLP system.

Incidence and Risk Factors for the Development of Axial Symptoms Following Posterior Single-Door Laminoplasty: A Retrospective Analysis.

OBJECTIVE: Posterior single-door laminoplasty is a widely practiced clinical procedure, but the occurrence of postoperative axial syndrome (AS) remains a significant concern. The aim of this study was to identify risk factors associated with AS and develop a risk prediction model. METHODS: Clinical data from 226 patients who underwent posterior single-door laminoplasty between June 2017 and June 2022 were collected. Through Logistic model analysis, the risk factors of AS are clarified and the intensity of each risk factor is explained in the form of forest plot. Subsequently, we constructed a predictive model and plotted receiver operating characteristic curves to assess the model's predictive value. RESULTS: In the end, 87 cases were diagnosed with AS, resulting in an incidence rate of 38.5%. Logistic regression analysis revealed that preoperative encroachment rate of anterior spinal canal (pre-op ERASC), intraoperative facet joints destruction, intraoperative open-door angle, postoperative loss of cervical curvature, and postoperative loss of cervical range of motion were independent risk factors for AS. Conversely, preoperative cervical curvature (pre-op CC) and postoperation early function training were protective factors against AS. The Youden index indicated that the cutoff values for pre-op ERASC and pre-op CC were 26.6°and 16.5, respectively. The risk prediction model for AS was constructed and a nomogram was plotted. The model has high clinical value. CONCLUSIONS: Pre-op ERASC, pre-op CC, intraoperative facet joints destruction, intraoperative open-door angle, postoperative loss of cervical curvature, postoperative loss of cervical range of motion, and postoperation early function training are independent influencing factors for AS occurrence. The risk model has good practicability.

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.