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Abstract Background and objectives Cauda equina syndrome with retention (CESR) is a severe lumbar condition characterized by painless urine retention due to cauda equina nerve injury. The standard treatment, posterior lumbar interbody fusion (PLIF), often yields suboptimal results. This study aims to compare the clinical safety and efficacy of a novel technique, capsule lumbar interbody fusion (CLIF), with PLIF in CESR patients, hypothesizing that CLIF can enhance neurological recovery by reducing nerve tension. Methods A single-center, retrospective study was conducted on 83 patients with CESR due to lumbar disc herniation, who underwent either PLIF (n = 44) or CLIF (n = 39). Patients were assessed preoperatively and at 3, 12, and 24 months postoperatively using the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), International Consultation on Incontinence Questionnaire Short Form (ICI-Q-SF), and Rintala score. Urodynamic studies and nerve tension measurements were also performed. Statistical analysis included t tests, Mann–Whitney U tests, and Spearman’s correlation. Results Both groups showed significant postoperative improvements, but the CLIF group had superior outcomes. At 12 months, the CLIF group had lower VAS scores (1.15 ± 0.84 vs. 1.68 ± 0.60, p = 0.001) and ODI scores (23.31 ± 7.51 vs. 28.30 ± 8.26, p = 0.005). At 24 months, the CLIF group continued to show better results with ODI scores (15.97 ± 6.43 vs. 22.11 ± 6.41, p

Objectives Dysphagia, an impairment in swallowing, is a frequent and debilitating complication for patients undergoing anterior cervical discectomy and fusion (ACDF), a common surgical treatment for degenerative cervical myelopathy (DCM). This retrospective study aimed to assess the efficacy of modified tracheal traction exercise (MTTE) in alleviating postoperative dysphagia and improving clinical outcomes for these patients. Methods A cohort of 143 patients underwent multilevel fusions, equally distributed between MTTE (n = 75) and traditional tracheal traction exercise (TTTE) (n = 68) groups. Demographic parity was observed in gender distribution, age averages (MTTE: 51.43 ± 11.25 years; TTTE: 52.35 ± 10.43 years), body mass index (BMI), comorbidities, fusion segments, and preoperative hospitalization days. Surgical duration differences were assessed. Clinical outcomes, dysphagia incidence, blood loss, postoperative complications, Cervical Japanese Orthopedic Association (c‐JOA) scores, and functional outcome swallowing scale evaluations were conducted. Univariate and multivariate logistic regression analyses were used to explore factors influencing dysphagia. Results Modified tracheal traction exercise demonstrated advantages with a significantly lower dysphagia incidence (25.33% vs. 44.12%, p = 0.018), reduced blood loss (102.03 ± 17.04 vs. 113.46 ± 14.92, p

Objective For precise and minimally invasive treatment of ossification of the posterior longitudinal ligament of the cervical spine, the lifting segment is minimized, anterior controllable antedisplacement and fusion (ACAF) was refined and improved. In addition, the development of appropriate surgical procedures for the ossification of each segment was rarely reported. Therefore, this study aimed to compare the efficacy and safety of hybrid anterior controlled antedisplacement fusion (Hybrid ACAF) with laminoplasty for multilevel ossification of the posterior longitudinal ligament (OPLL). Methods Between May 2018 and May 2021, 70 patients with multilevel OPLL were divided into a hybrid ACAF group and a laminoplasty group according to surgical methods. All patients were followed up for at least 1 year. Japanese Orthopaedic Association (JOA) score and recovery rate (JOARR), (VAS, NDI) score and C2–C7 Cobb angle, the sagittal vertical axis of the neck (SVA), and complications (cerebrospinal fluid leakage, C5 paralysis, etc.) were compared between the two groups by t test or non‐parametric test. Results The operation time of hybrid ACAF was longer. C5 paralysis and axial pain were more common in the laminoplasty group, while dysphagia and hoarseness were more common in the hybrid ACAF group. At the last follow‐up, the hybrid ACAF group had better recovery and maintenance of cervical lordosis and sagittal plane balance and a higher JOA score and recovery rate than the laminoplasty group. Conclusions Hybrid ACAF can reduce the number of vertebral bodies and expand the decompression range, which is safe, effective, and tailored to local conditions. Compared with laminoplasty, hybrid ACAF is a precise alternative for patients with OPLL.

Purpose Multilevel cervical spondylotic myelopathy poses significant challenges in selecting optimal surgical approaches, warranting a comprehensive understanding of their biomechanical impacts. Given the lack of consensus regarding the most effective technique, this study aims to fill this critical knowledge gap by rigorously assessing and comparing the biomechanical properties of three distinct surgical interventions, including anterior controllable antedisplacement and fusion (ACAF), anterior cervical corpectomy decompression and fusion (ACCF), and anterior cervical discectomy and fusion (ACDF). The study offers pivotal insights to enhance treatment precision and patient outcomes. Methods The construction of the cervical spine model involved a detailed process using CT data, specialized software (Mimics, Geomagic Studio, and Hypermesh) and material properties obtained from prior studies. Surgical instruments were modeled (titanium mesh, anterior cervical plate, interbody cage, and self‐tapping screws) to simulate three surgical approaches: ACAF, ACCF, and ACDF, each with specific procedures replicating clinical protocols. A 75‐N follower load with 2 Nm was applied to simulate biomechanical effects. Results The range of motion decreased more after surgery for ACAF and ACDF than for ACCF, especially in flexion and lateral bending. ACCF have higher stress peaks in the fixation system than those of ACAF and ACDF, especially in flexion. The maximum von Mises stresses of the bone–screw interfaces at C3 of ACCF were higher than those of ACAF and ACDF. The maximum von Mises stresses of the bone–screw interfaces at C6 of ACDF were much higher than those of ACAF and ACCF. The maximum von Mises stresses of the grafts of ACCF and ACAF were much higher than those of ACDF. The maximum von Mises stresses of the endplate of ACCF were much higher than those of ACAF and ACDF. Conclusion The ACAF and ACDF models demonstrated superior cervical reconstruction stability over the ACCF model. ACAF exhibited lower risks of internal fixation failure and cage subsidence compared to ACCF, making it a promising approach. However, while ACAF revealed improved stability over ACCF, higher rates of subsidence and internal fixation failure persisted compared to ACDF, suggesting the need for further exploration of ACAF's long‐term efficacy and potential improvements in clinical outcomes.

Abstract Background New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis. Methods and analysis This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis populations in the study. Conclusion This study is designed to investigate the clinical outcomes of modified LIF sequences in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified “fixation-fusion” sequence of LIF surgery is effective in treating lumbar spinal stenosis. Trial registration http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507.

Abstract Background Fuzi decoction (FZD), a traditional Chinese medicine formula, was used to treat musculoskeletal diseases by warming channels, strengthening yang and dispelling pathogenic cold and dampness. In clinical practice, FZD has been used to treat rheumatoid arthritis and osteoarthritis. It alleviated osteoarticular disorders through ameliorating the degradation of cartilage and improving meniscal damage in osteoarthritis, while its roles and mechanisms in the treatment of bone loss diseases remain unclear. This study aims to investigate the underlying mechanisms of FZD in treating osteoporosis using an integrative method of network pharmacology and experimental study. Methods In this study, network pharmacology was used to predict the core targets and potential pathways of the bioactive ingredients of FZD to attenuate osteoporosis. Molecular docking was performed to evaluate the interactions between core compounds and key targets. In addition, both cell and animal experiments were carried out to validate the role and potential mechanism in treating osteoporosis. Results In the present study, data revealed that kaempferol, beta-sitosterol, stigmasterol, fumarine, and (+)-catechin may be the primary bioactive ingredients of FZD in the treatment of osteoporosis, which were closely associated with the osteoporosis-related targets. And the KEGG results indicated that the NF-κB pathway was closely associated with the function of FZD in treating osteoporosis. In addition, in vivo demonstrated that FZD ameliorated osteoporosis. In vitro experiments showed that the pro-apoptotic factors indicators including CASP3 and BAX were decreased by FZD and the anti-apoptotic factor BCL2 was increased by FZD. In addition, FZD significantly suppressed the osteoclast differentiation in culture and the expression levels of osteoclast-related genes including TRAF6, CTSK, and MMP9. And the NF-κB pathway was confirmed, via in vitro experiment, to be involved in osteoclast differentiation. Conclusions This study demonstrated that FZD played a pivotal role in suppressing the osteoclast differentiation via regulating the NF-κB pathway, indicating that FZD could be a promising antiosteoporosis drug and deserve further investigation.

Objective It is clinically important for pedicle screws to be placed quickly and accurately. Misplacement of pedicle screws results in various complications. However, the incidence of complications varies greatly due to the different professional titles of physicians and surgical experience. Therefore, physicians must minimize pedicle screw dislocation. This study aims to compare the three nail placement methods in this study, and explore which method is the best for determining the anatomical landmarks and vertical trajectories. Methods This study involved 70 patients with moderate idiopathic scoliosis who had undergone deformity correction surgery between 2018 and 2021. Two spine surgeons used three techniques (preoperative computed tomography scan [CTS], visual inspection‐X‐freehand [XFH], and intraoperative detection [ID] of anatomical landmarks) to locate pedicle screws. The techniques used include visual inspection for 287 screws in 21 patients, preoperative planning for 346 screws in 26 patients, and intraoperative probing for 309 screws in 23 patients. Observers assessed screw conditions based on intraoperative CT scans (Grade A, B, C, D). Results There were no significant differences between the three groups in terms of age, sex, and degree of deformity. We found that 68.64% of screws in the XFH group, 67.63% in the CTS group, and 77.99% in the ID group were placed within the pedicle margins (grade A). On the other hand, 6.27% of screws in the XFH group, 4.33% in the CTS group, and 6.15% in the ID group were considered misplaced (grades C and D). The results show that the total amount of upper thoracic pedicle screws was fewer, meanwhile their placement accuracy was lower. The three methods used in this study had similar accuracy in intermediate physicians (P > 0.05). Compared with intermediate physicians, the placement accuracy of three techniques in senior physicians was higher. The intraoperative detection group was better than the other two groups in the good rate and accuracy of nail placement (P

Intervertebral disc degeneration (IVDD) is a degenerative disease accompanied by the loss of nucleus pulposus cells and the degradation of extracellular matrix (ECM), which tends to be associated with lower back pain. The ECM and various types of cell death in IVDD are regulated by multiple factors, such as inflammatory responses and oxidative stress. The glutathione (GSH) redox system is the most important antioxidant defense system in cells. GSH is one of the most abundant thiol antioxidants in mammalian cells, which functions directly and indirectly by scavenging peroxides through the GSH redox system. In these reactions, GSH is oxidized by electrophilic substances, such as reactive oxygen species and free radicals, to form glutathione disulfide to exert antioxidative effects. It has been reported that GSH can protect cells against the damage of oxidative stress and various pathophysiological stimulus that can lead to different types of cell death. In addition, it was reported that the level of GSH widely participates in apoptosis, autophagy, ferroptosis, and oxidative stress in many diseases including osteoarthritis and IVDD. Therefore, we summarized the effects of GSH on ECM metabolism and cells’ functions during IVDD. In addition, we summarized the regulatory effects of small molecule compounds on GSH to explore potential ways to regulate the level of GSH. Better understanding the underlying role of GSH in regulating IVDD will facilitate the goal of preventing and retarding the progress of IVDD in the future.

Strain-dependency of permeability is a key feature for coupled multiphysics phenomena during heavy oil production under steam stimulation. This feature is also the basis for accurate estimation of steam needed to properly stimulate a given target heavy oil block. In this study, a fully coupled thermal-hydro-mechanical model is established and applied to the numerical simulation of steam injection in a block of western China Xinjiang region's heavy oil field. Strain-dependent relationships have been established for hydraulic conductivity as well as Young's modulus of reservoir formations. The distribution of reservoir temperature field and pore pressure field is obtained, and a quantitative evaluation of steam injection effectiveness is provided. The principal contents include: 1) A simplified fully coupled thermal-hydro-mechanical model for heavy oil reservoir under steam injection is presented. The model incorporates strain-dependent characteristics for rock's permeability/hydraulic conductivity and elastic modulus. 2) The simplified fully coupled model is implemented via the user subroutines of Abaqus software, and 3D finite element simulations are conducted for the steam stimulation operation and oil production processes in the heavy oil block. The temperature field and pore pressure field of the reservoir are obtained under given production history and steam injection conditions. These numerical results have provided an accurate evaluation of steam injection effectiveness. These numerical results indicate that: 1) The original design of steam injection volume and soak time is insufficient to connect the temperature rise regions around wells A1 and A2 in the block in order to get ideal production rate. The temperature rise data obtained from monitoring wells verify the accuracy of the calculation results, demonstrating the accuracy and practicality of the proposed theoretical model. 2) It is found that the maximum local pore pressure induced by steam injection may exceed the bottomhole pressure of injection wells. This is due to the thermal expansion of both solids and pore fluids caused by rapid temperature rise. 3) For the target reservoir, numerical results indicate that further steam injection for 17 days on top of the original design will connect the temperature rise regions around wells A1 and A2, and the minimum temperature at various points between wells will exceed 40 °C.

Abstract Background Surgical site infection (SSI) is the most common complications in spinal surgery. In SSI, non-superficial surgical site infections are more likely to result in poor clinical outcomes. It has been reported that there are multiple factors contributing to postoperative non-superficial SSI, but still remains controversial. Therefore, the aim of this meta-analysis is to investigate the potential risk factors for non-superficial SSI following spinal surgery. Methods A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until September 2022. According to the inclusion and exclusion criteria, two evaluators independently conducted literature screening, data extraction and quality evaluation of the obtained literature. The Newcastle–Ottawa Scale (NOS) score was used for quality evaluation, and meta-analysis was performed by STATA 14.0 software. Results A total of 3660 relevant articles were initially identified and 11 articles were finally included in this study for data extraction and meta-analysis. The results of meta-analysis showed that the diabetes mellitus, obesity, using steroids, drainage time and operative time were related to the non-superficial SSI. The OR values (95%CI) of these five factors were 1.527 (1.196, 1.949); 1.314 (1.128, 1.532); 1.687(1.317, 2.162); 1.531(1.313, 1.786) and 4.255(2.612, 6.932) respectively. Conclusions Diabetes mellitus, obesity, using steroids, drainage time and operative time are the current risk factors for non-superficial SSI following spinal surgery. In this study, operative time is the most important risk factor resulting in postoperative SSI.

Abstract Background As an important part of spinal fusion procedure, the selection of fusion cage size is closely related to the curative effect of the surgery. It mainly depends on the clinical experience of surgeons, and there is still a lack of objective standards. The purpose of this study is to propose the concept of relative intervertebral tension (RIT) for the first time and its grading standards to improve the surgical procedures of lumbar interbody fusion. Methods This retrospective study was conducted from January 2018 to July 2019. A total of 83 eligible patients including 45 men and 38 women with lumbar degenerative disease underwent transforaminal lumbar interbody fusion (TLIF) were included in this study. A total of 151 fusion segments were divided into group A, group B and group C according to the grading standards of RIT. In addition, parameters of intervertebral space angle (ISA), intervertebral space height (ISH), intervertebral space foramen (IFH), fusion rates, cage-related complications and cage heights were also compared among the three groups. Results The ISA in group A was the smallest among three groups in contrast with group C with largest ISA at the final follow-up(P 0.05), and a certain correlation between ISH and RIT was also observed. Conclusions The concept of RIT and the application of its clinical grading standards could simplify the surgical procedures of spinal fusion and reduce cage-related complications.

Study Design: A retrospective study. Purpose: To firstly introduce a new surgical technique named as selective fenestration and axial decompression (SFAD) to improve the surgical treatment effects of lumbar degenerative diseases. Overview of literature: Posterior lumbar laminectomy and interbody fusion (LIF) is a standard surgical method for the treatment of lumbar degenerative diseases. However, its application has some limitations, and the incidence of spinal cord nerve injury is relatively high. Methods: This retrospective clinical study was conducted from January 2018 to February2020. A total of 101 eligible patients including 62 men and 39 women with lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) underwent LIF or SFAD were enrolled in this study. The average postoperative follow-up period of the LIF and SFAD groups were 20.1 ± 3.7 months and 19.7 ± 4.1 months, respectively. The clinical effects, imaging manifestation, and postoperative complications in LIF and SFAD groups were analyzed. Results: The operative time, blood loss and hospital stay in SFAD group were significantly lower than those in LIF group (P 0.05). Similarly, improvements of cobb angle of operated segment, intervertebral space height (ISH), intervertebral space foramen (IFH) and lumbar lordosis (LL) showed no statistical difference between the two groups (P > 0.05). Finally, the prevalence of complication rates in LIF group were significantly higher than the SFAD group during the follow-up period (P

Objective To evaluate the clinical value of diabetes mellitus for diagnosis and postoperative prognosis in patients with cervical spondylotic myelopathy undergoing anterior decompression and fusion. Methods A total of 84 Patients (50 males and 34 females) who underwent anterior decompression and fusion were reviewed in this single‐center retrospective study. The patients were divided into two groups (44 patients in the diabetes mellitus group and 40 in the non‐diabetic group). Clinical manifestations were evaluated, including characteristics baseline, clinical tests, MRI information, clinical scores, and complications. The predictive effect of diabetes mellitus on clinical scores were assessed via the receiver operating characteristic curve. The correlation between the severity of diabetes mellitus and neurological function recovery was estimated using the Pearson correlation coefficient. Results Patients with diabetes mellitus exhibited a higher ratio of hyperintensity of the spinal cord (P 0.05). Conclusion This present study revealed that the neurological impairment caused by diabetes mellitus in patients undergoing anterior decompression and fusion does not only affect postoperative functional recovery but also interferes with the preoperative clinical manifestations, especially the sensory function in the upper and lower limbs.

Abstract Purpose This retrospective study was performed to analyze the clinical effects and complications of LSFCF in the surgical treatment of DLS combined with lumbar spinal stenosis (LSS). Methods A total of 26 eligible patients (mean age, 64.73 y; 17 men, 9 women) with DLS combined with LSS were included and LSFCF surgery was performed. An independent spine surgeon retrospectively reviewed the medical records and radiographs of all patients to evaluate surgical data and surgery-related complications. Preoperative, postoperative, and follow-up questionnaires were obtained to assess clinical outcomes. Results The average follow-up period of this study was 20.14 ± 5.21 months. The operation time and blood loss of patients underwent LSFCF were 129.33 ± 15.74 min and 356.13 ± 21.28 ml. The clinical effects of all patients in terms of visual analogue scale (VAS) and Oswestry disability index (ODI) have been significantly improved at the final follow-up postoperatively (P

Objective: Lumbar decompression surgery is an effective treatment for foot drop caused by LDD, but there is controversy about the prognostic factors affecting its efficacy. This study aimed to investigate the factors influencing the surgical outcome of foot drop due to LDD. Methods: A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until May 2022. Two reviewers independently screened the literature, extracted data, and evaluated the quality of the studies based on the inclusion and exclusion criteria. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and STATA 16.0 software was used for meta-analysis. Results: A total of 730 relevant articles were initially identified and 9 articles were finally included in this study for data extraction and mea-analysis. The results of metaanalysis showed that patients with preoperative moderate muscle strength (2-3/5 on the Medical Research Council scale) had better prognosis compared to those with severe muscle weakness. Additionally, the presence of diabetes mellitus was associated with a poorer prognosis for patients with foot drop due to LDD. The OR values (95%CI) of these two factors were 5.882 (4.449, 7.776) and 5.657 (2.094,15.280) respectively. Conclusions: Patients with moderate muscle strength have a better prognosis compared to those with severe muscle weakness. The presence of diabetes mellitus is associated with a poorer prognosis for patients with foot drop due to LDD. These factors should be considered when predicting the surgical outcome of foot drop due to LDD.

Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3−/−) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11−/−) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD.

Objective: Cage migration is a rare complication after lumbar fusion surgery, and it is also the cause of lumbar revision surgery. Previous studies have reported that many influencing factors can increase the incidence of cage migration. However, there still remains controversial. The current study was conducted to investigate the risk factors influencing incidence of cage migration. Methods: A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until July 2022. According to the inclusion and exclusion criteria, two evaluators independently conducted literature screening, data extraction and quality evaluation of the obtained literature. The Newcastle–Ottawa Scale (NOS) score was used for quality evaluation, and meta-analysis was performed by STATA 16.0 software. Results: A total of 2126 relevant articles were initially identified, and 7 articles were finally included in this study for data extraction and meta-analysis. The results of meta-analysis showed that the bony endplate injury, pear-shaped disc, and screw loosening are significantly correlated with cage migration. The OR values (95%CI) of the three factors were 7.170 (3.015, 17.051), 8.056 (4.050, 16.023), and 12.840 (3.570, 46.177) respectively. Conclusion: Bony endplate injury, pear-shaped disc, and screw loosening are the current risk factors for cage migration postoperatively.

Objective To determine if there is a difference in either the cervical alignment or the clinical outcomes in cervical ossification of the posterior longitudinal ligament (OPLL) patients who underwent laminectomy with instrumented fusion (LIF) ending at C6, C7, or proximal thoracic spine for the treatment of multilevel OPLL, and to find out the appropriate distal fusion level. Methods This was a single‐center retrospective study. In total, 36 patients with cervical OPLL who underwent three or more level LIF in our institution between January 2015 and January 2017 were enrolled. They were divided into three groups according to their distal ends: C6 (nine females and 11 males, 60.45 ± 9.68 years old), C7 (four females and six males, 61.60 ± 10.29 years old), and T‐group (two females and four males, 64.33 ± 8.12 years old). Radiographic (compression level, classification of OPLL, occupying rate, C2‐7 cobb angle, C2‐7 sagittal vertical axis, and fusion level) and clinical outcomes (NDI score, operative time, and blood loss) were compared. Predictors of postoperative sagittal imbalance were also identified according to if the postoperative C2‐7 SVA was greater than 40 mm. The sensitivity and specificity of preoperative parameters predicting postoperative cervical stability were evaluated via the receiver operating characteristic (ROC) curve. Results All patients were followed up at least 1 year. The blood loss in T group was significantly more than C6 or C7 group. The length of fusion level became significantly longer when the caudal level extended to the thoracic spine. The age, preoperative SVA, and NDI score at follow‐up were significantly greater in the imbalance group. At the final follow‐up, the cervical lordosis tended to be straight and the C2‐7 SVA tended to be greater when the caudal level of fusion was extended to upper thoracic segment. Further ROC curve analysis suggested that patients’ age had a sensitivity of 75.00%, specificity of 79.17% for cervical stability, and the AUC was 0.844 (P 67 years) with great preoperative SVA (>30 mm), terminating at C6 was recommended to limit the invasion of cervical extensor muscles, provided the decompression was adequate.

Abstract Background Neovasculogenesis is characteristic of herniated lumbar discs, in which extruded nucleus pulposus is prone to heme iron-induced cytotoxicity (increased oxidative stress causing ferroptosis). However, recent analyses of neovascularization are very complicated, and the mechanism of action is rarely reported. Methods Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) was performed to analyze human herniated and nonherniated nucleus pulposus. Then, the clinical relevance of the MALDI-TOF MS results and Pfirrmann classification of the degenerative nucleus pulposus were analyzed. To explore the mechanism, the heme-induced ferroptosis effect was evaluated at both the tissue and cell levels using high-resolution MALDI-TOF MS and molecular biology methods. Results The spectra revealed that hemoglobin (Hb) and heme signals were greatly increased, thus serving as predictors of vasculogenesis in herniated nucleus pulposus. The clinical relevance analysis demonstrated that the intensity of Hb and heme peaks was closely related to the Pfirrmann classification of degenerative nucleus pulposus. Mechanistically, increased heme catabolism and downregulation of glutathione peroxidase 4 (GPX4) levels were detected in herniated nucleus pulposus, reflecting iron-dependent cell death or ferroptosis. Iron levels was also increased in herniated nucleus pulposus compared with that in nonherniated nucleus pulposus. Furthermore, accuracy mass measurements confirmed that the levels of ferroptosis-related metabolites, such as glutathione, arachidonic acid (AA), sphinganine, polyunsaturated fatty acid (PUFA), and tricarboxylic acid (TCA) cycle metabolites, were significantly different between herniated and nonherniated tissues, indicating that the interior of the herniated tissues is a pro-oxidant environment. Moreover, heme-induced ferroptosis was verified in human nucleus pulposus cells (HNPCs), and the underlying mechanism might be associated with the Notch pathway. Conclusions Neovascularization in herniated nucleus pulposus may expose tissues to high levels of heme, which can induce cytotoxicity and ferroptosis within tissues and accelerate the progressive degeneration of herniated nucleus pulposus. This study is beneficial for understanding the pathological mechanism of herniated nucleus pulposus and facilitating the development of nonoperative interventions for treating lumbar disc herniation (LDH).

Abstract Background In treating patients with cervical ossification of the posterior longitudinal ligament (COPLL), a novel surgery technique - anterior controllable antedisplacement and fusion (ACAF) suggested promising clinical benefits in recent exploratory studies. Methods This is a multicentre, randomized, open-label, parallel-group, active controlled trial that will compare the clinical benefits of ACAF versus conventional posterior laminoplasty (LAMP) in severe COPLL patients. A total of 164 patients will be enrolled and randomized in a 1:1 ratio to either ACAF or LAMP group. The primary efficacy measure is cervical- Japanese Orthopaedic Association (C-JOA) recovery rate at 12 months post operation, which is to be derived by Hirabayashi’s method from JOA data (range, 0 [worst] to 17 [normal condition]). Other important secondary efficacy endpoints include visual analogue scale (VAS) pain score (range, 0 [no pain] to 10 [most severe]), 10-item neck disability index (NDI, a total range of 0 to 50 points, the highest index the worst) and 6-level Nurick disability grade (range, 0 [mild] to 5 [severe]). Safety endpoints including adverse events, perioperative complications, and adverse events of special interest will also be assessed in this study. Full analysis set for baseline and efficacy data analyses according to the intention-to-treat principle will be established as the primary analysis population. Analysis of covariance (ANCOVA) will be used to analyze the C-JOA recovery rate, with random stratification factors (if appropriate) and the treatment group as fixed factors, and the baseline level of C-JOA score as covariate. Discussion This study is designed to demonstrate the clinical benefits of ACAF as compared to conventional LAMP in COPLL patients. It will provide clinical evidence that the novel surgery technique – ACAF might be more favorable in treating patients with severe cervical ossification of the posterior longitudinal ligament. (Words: 290). Trial registration ClinicalTrials.gov number, NCT04968028 .

Abnormal angiogenesis and innervation in avascular discs during lumbar disc degeneration (LDD) cause severe back pain. These pathological alterations in the degenerating discs are induced by cytokines partially produced and secreted by inflammatory cells, among which macrophages are the most frequently ones detected at the legion site. However, the role of macrophages as well as their polarization in regulation of innervation and angiogenesis in the degenerating discs is unclear. In this study, we analyzed macrophages in the degenerating discs from patients and detected a specific macrophage subtype that expresses high levels of vascular endothelial growth factor A (VEGF-A). Co-expression of M2 macrophage markers in this macrophage subtype suggested that they were a M2d-like subtype. High levels of VEGF-A and genes associated with angiogenesis were also detected in LDD specimens compared to control heathy discs from a public database, consistent with our finding. Moreover, the levels of VEGF-A in disc macrophages were strongly correlated to the pain score of the examined patients, but not to the Thompson classification of the degeneration level of the patients. In vitro, overexpressing VEGF-A in macrophages increased the tube formation, proliferation and migration of co-cultured endothelial cells, and increased the innervation of embryonic spinal cord explant into the co-cultured area for macrophages and skeletal myocytes. In vivo, an orthotopic injection of adeno-associated virus carrying siRNA for VEGF-A under a macrophage-specific CD68 promoter significantly reduced the number of VEGF-A-positive disc macrophages and alleviated the pain in LDD-mice. Together, these data suggest that inhibition of angiogenetic potential of macrophages may reduce disc degeneration-associated pain through suppression of angiogenesis and innervation, as a promising therapy for LDD-associated pain.

Abstract Study design This is a prospective case-controlled study. Background To analyze the postoperative axial pain and cage subsidence of patients presenting with cervical spondylotic myelopathy (CSM) after a modified procedure of ACDF (mACDF). Methods Ninety patients with CSM were prospectively collected from 2014 to 2018. The patients were divided into spread group and non-spread group (48:42 ratio) according to the cage placement with or without releasing the Caspar cervical retractor after decompression. Spread group received conventional ACDF and non-spread group received mACDF. Patients were followed-up for at least 24 months after surgery. Radiologic data, including height of intervertebral space and Cobb Angle, were collected. Nervous system function was obtained using JOA scores, and level of pain was assessed using VAS scores. Results A total of 90 patients were enrolled and the patients were divided into spread group (n = 48) and none-spread group(n = 42). Cage subsidence of (spread group vs none-spread group) was (0.82 ± 0.68 vs 0.58 ± 0.81) mm, (0.64 ± 0.77 vs 0.34 ± 0.46) mm, (0.48 ± 0.43 vs 0.25 ± 0.28) mm, and (0.45 ± 0.47 vs 0.17 ± 0.32) mm at 3 months, 6 months, 12 months and 24 months, respectively. The period exhibiting the most decrease of the height of intervertebral space was 3 months postoperatively. However, there was no statistical difference in the height of intervertebral space, JOA or VAS scores at the final follow-up between the two groups. Conclusions The mACDF can avoid excessive distraction by releasing the Caspar Cervical retractor, restore the “natural height” of cervical vertebra, relieve immediate pain after surgery, and prevent rapid Cage subsidence and the loss of cervical curvature.

Bone homeostasis has been a dynamic equilibrium between osteoclasts (OCs) and osteoblasts (OBs). However, excessive activation of OCs could disturb the bone homeostasis. As a result, effective medical interventions for patients are greatly demanding. NO/guanylate cyclase (GC)/cGMP signaling cascade has been previously reported to regulate bone metabolism, and GC plays a significantly critical role. Vericiguat, as a novel oral soluble guanylate cyclase (sGC) stimulator, has been firstly reported in 2020 to treat patients with heart failure. Nevertheless, the biological effects of Vericiguat on the function of OCs have not yet been explored. In this present study, we found that Vericiguat with the concentration between 0 and 8 μM was noncytotoxic to bone marrow-derived monocyte-macrophage lineage (BMMs). Vericiguat could enhance the differentiation of OCs at concentration of 500 nM, whereas it inhibited OC differentiation at 8 μM. In addition, Vericiguat also showed dual effects on OC fusion and bone resorption in a dose-dependent manner. Furthermore, a molecular assay suggested that the dual regulatory effects of Vericiguat on OCs were mediated by the bidirectional activation of the IκB-α/NF-κB signaling pathway. Taken together, our present study demonstrated the dual effects of Vericiguat on the formation of functional OCs. The regulatory effects of Vericiguat on OCs were achieved by the bidirectional modulation of the IκB-α/NF-κB signaling pathway, and a potential balance between the IκB-α/NF-κB signaling pathway and sGC/cGMP/VASP may exist.

Cuttings accumulation in horizontal drilling is one of the main reasons for high drilling torque and drag and serious backing pressure and consequently influencing the rate of penetration (ROP), so inhibiting the generation of cuttings bed and keeping the hole clean is an important prerequisite to ensure the smooth and safe drilling of horizontal section. In order to master the formation mechanism of cuttings bed and reveal the influence law of influencing factors, based on the three-layer cuttings bed migration model and the two-phase solid-liquid flow theory, this paper establishes a numerical simulation method for cuttings migration characteristics in the annulus of horizontal wells, reveals the cuttings concentration distribution law and migration characteristics in the horizontal well section, and fits the engineering prediction model of cuttings bed height considering many factors such as geology, engineering, and fluid body according to the simulation results. The analysis of sensitive factors shows that the rate of penetrating, cuttings density, and drill pipe eccentricity is not conducive to borehole cleaning, and cuttings are easy to accumulate to form cuttings bed; increasing the drilling fluid density, displacement, and drill pipe speed is conducive to borehole cleaning and reducing the height of cuttings bed. The research shows that within the range of normal construction parameters, the error of the horizontal cuttings height prediction model is less than 10%, which can meet the needs of engineering analysis. The model provides convenience for engineering applications.

Intervertebral disc degeneration (IVDD) has been a complex disorder resulted from genetic and environmental risk factors. The aim of this study was to identify the risk factors associated with IVDD in orthopaedic patients and develop a prediction model for predicting the risk of IVDD. A total of 309 patients were retrospectively included in the study and randomly divided into the training group and the validation group. The least absolute shrinkage and selection operator regression (LASSO) and the univariate logistic regression analysis were used to optimize factors selection for the IVDD risk model. Multivariable logistic regression analysis was used to establish a predicting nomogram model incorporating the factors. In addition, discrimination, calibration, and clinical usefulness of the nomogram model were evaluated via the C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). Then, based on the results above, the relationship between IVDD and angiotensin II (AngII) level in peripheral blood was examined prospectively. The predictors of the nomogram include age, sex, hypertension, diabetes, gout, working posture, and exercising hours per week. The C-index values of the training and validation groups were 0.916 (95% CI, 0.876-0.956) and 0.949 (95% CI, 0.909-0.989), respectively, which indicated that the model displayed good discrimination. In addition, the area under the curve (AUC) values of the ROC curve of the training and the validation group were 0.815 (95% CI, 0.759-0.870) and 0.805 (95% CI, 0.718-0.892), respectively, revealing the satisfactory discrimination performance of the model. The prospective investigation showed that the average AngII level in the degenerated group (97.62±44.02 pg/mL) was significantly higher than that in the nondegenerated group (52.91±9.01 pg/mL) (p

The aim of this study was to propose the workflow for integrated analysis of the 3D geostress and 1D geomechanics of an exploration in a new gas field. This integrated analysis will allow for problems associated with the inaccuracy of 1D geomechanical analysis to be overcome in a region with obvious anticline/syncline structures. The 1D geomechanical analysis of the well in the exploration of a new gas field mainly included the prediction of pore pressure and calculation of the mud weight window for safe drilling. In general, this integrated workflow included both a method for pore pressure prediction and a method for the calculation of the mud weight window, with the numerical solution of 3D geostress plus the interval velocity of formations. The procedure for the calculation of the 3D geostress of a target block was also introduced. Numerical solution of the 3D geostress of the target gas field, as well as solutions of 1D geomechanical analysis, have demonstrated the efficiency and practical use of the proposed theory in the successful drilling of the LT-1 well in the Junggar Basin, Xinjiang, China. For this LT-1 well in the target TS block, there was no logging data to refer to when predicting the pore pressure of undrilled formations. Only 3D geostress could be used to calculate the mud weight window. Influences of anticline structures were considered in the calculation of 3D geostress. Since the accuracy of the numerical solution of 3D geostress is higher than the accuracy of the 1D geostress solution for a single well analysis, the results of pore pressure and the mud weight window are more accurate than those obtained with conventional 1D geostress analysis. Details of the finite element modeling of the 3D geostress field of the TS block is presented along with the solution of the 3D geostress field. With the data of the interval velocity of formations and 3D geostress solution of the TS block, pore pressure prediction was carried out for the 7000 m-deep pilot LT-1 well. Finally, calculations were performed for the values of the mud weight window of the LT-1 well.

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which imposes massive clinical and socioeconomic burdens. Previous studies have demonstrated that oxidative stress and inflammation-induced senescence and apoptosis of nucleus pulposus cells (NPCs) are the main cellular processes that cause IDD. Arginase II (ARG2), an enzyme involved in a variety of pathological processes, including cellular senescence, apoptosis, oxidative stress, and inflammation, has been shown to promote degeneration in several degenerative diseases, including osteoarticular diseases. Based on previous studies, we hypothesized that ARG2 deficiency might be conducive to the treatment of IDD by inhibiting the dyshomeostasis of the extracellular matrix (ECM), and the oxidative stress and inflammatory response-induced senescence and apoptosis via NF-κB. In this study, we found that ARG2 deficiency inhibited senescence and apoptosis of NPCs, and degeneration of the ECM induced by oxidative stress and the inflammatory response. Similar results were found with the selective NF-κB pathway inhibitor JSH-23. In contrast, overexpression of ARG2 had the opposite effect. Taken together, our results suggest that ARG2 deficiency prevents IDD via NF-κB, and may therefore, be a potential therapeutic strategy for IDD.

Accurate surge pressure prediction during tripping is significant to ensure drilling safety. Based on the theory of wellbore hydraulics and heat transfer, a surge pressure prediction model considering the influence of HTHP and joints is established in this paper. The finite difference method is used to solve the wellbore flow model. Compared with the measured surge pressure, it was found that the error between the predicted and measured values after considering the above factors was only 0.89%. The influence of dimensionless joint outer diameter, joint length and drill string tripping speed on the surge pressure was further analyzed. The results show that the existence of joints increases the surge pressure. When the dimensionless joint outer diameter was increased from 0.70 to 0.91, the surge pressure increased by 76%. Neglecting the effect of the joint will cause a large error in calculating the surge pressure. In addition, the surge pressure is positively correlated with the drill string tripping speed. However, with the decrease in drill string tripping speed, the surge pressure will gradually tend to a stable value. This study provides a theoretical reference for the hydraulic design of HTHP well tripping.

The Permian igneous rock in Shunbei Oilfield exhibits high rock strength, which results in a low rate of penetration (ROP) and shortens the cutter’s service life. It is necessary to analyze and evaluate the rock breaking effect of cutters. However, at this stage, the evaluation of the rock breaking effect has been limited to comparing the sizes of the mechanical specific energy (MSE), and the change in the rock breaking efficiency caused by the difference in the shape of the cutters’ surface has not been considered. Therefore, through the establishment of numerical simulation models of a circular cutter, bevel cutter, axe cutter, wedge cutter, and triangular cutter, the evaluation of the rock breaking efficiency of special-shaped cutters was completed. The results show that the triangular cutter and the wedge cutter are suitable for the front row cutter of the polycrystalline diamond compact bit (PDC); the triangular cutter is suitable for drilling into medium–hard formations, the wedge cutter is suitable for drilling into hard formations, and the bevel cutter is suitable for the back row cutter of the PDC, to assist other cutters in the process of rock breaking. The research results can provide the basis for the selection of PDC bit cutters and the design optimization of the bit.

The spatial imbalance between population growth, land use and housing supply is the central issue for regional coordination of urban agglomeration in China. Based on the panel data of 172 cities in 11 urban agglomerations from 2014 to 2017, this study uses the information entropy method and the spatial coupling coordination degree model to evaluate the quantitative interaction and spatial correlations between population growth, land use and housing supply. There are three key findings: (1) the main variation value of indicators has evolved from the quantity of housing supply to the quality of population growth, improving the quality of population growth has been the key factor to break the insufficient balance of indicators; (2) the coupling degree is high but the coordination degree is obviously low, the aggregation level of coupling coordination degree is generally middle, and there is obviously spatial polarization—improving the degree of coordination is the key point to break the inadequate balance of cities; (3) the coupling coordination degree is irregularly distributed in 11 urban agglomerations, the spatial correlation of coupling coordination degree is generally weak, improving the spatial coordination degree of urban agglomeration will contribute to improving the balanced sufficiency level, and the spatial coupling coordination degree is also expected to increase. This study presents a new perspective for exploring spatial coordination between population growth, land use and housing supply, which proposes a new approach to investigate quantitative interaction and spatial correlation of urban agglomeration in China.

BackgroundTraumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep), which has not yet been effectively cured. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment. However, the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of researches have begun to investigate the effect of PD-L1 on macrophages and microglia in recent years. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we proposed the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through regulating macrophages and microglia.MethodsThe mice SCI model was established to determine the changes in expression patterns of PD-L1. Meanwhile, we constructed PD-L1 knockout mice to observe differences in functional recovery and phenotypes of macrophages/microglia post-SCI.ResultsIn present study, PD-L1 was significantly upregulated after SCI and highly expressed on macrophages/microglia at the injury epicenter. PD-L1 knockout (KO) mice showed worse locomotor recovery and more serious pathological pain compared with wild-type (WT) mice. Furthermore, deletion of PD-L1 significantly increased the polarization of M1-like macrophages/microglia. Mechanistic analysis revealed that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2.ConclusionsOur observations implicate the involvement of PD-L1 in recovery of SCI and provide a new treatment strategy for the prevention and treatment of this traumatic condition.

Osteolytic bone disease is a condition of imbalanced bone homeostasis, characterized mainly by excessive bone-resorptive activity, which could predispose these populations, such as the old and postmenopausal women, to developing high risk of skeletal fragility and fracture. The nature of bone homeostasis is the coordination between the osteoblasts (OBs) and osteoclasts (OCs). Abnormal activation of osteoclasts (OCs) could compromise the bone homeostasis, constantly followed by a clutch of osteolytic diseases, including postmenopausal osteoporosis, osteoarthritis, and rheumatoid arthritis. Thus, it is imperatively urgent to explore effective medical interventions for patients. The traditional Chinese medicine (TCM) gamabufotalin (CS-6) is a newly identified natural product from Chansu and has been utilized for oncologic therapies owing to its good clinical efficacy with less adverse events. Previous study suggested that CS-6 could be a novel anti-osteoporotic agent. Nevertheless, whether CS-6 suppresses RANK-(receptor activator of nuclear factor-κ B ligand)/TRAF6 (TNF receptor-associated factor 6)-mediated downstream signaling activation in OCs, as well as the effects of CS-6 on OC differentiation in vivo, remains elusive. Therefore, in this present study, we aimed to explore the biological effects of CS-6 on osteoclastogenesis and RANKL-induced activation of related signaling pathways, and further to examine the potential therapeutic application in estrogen-deficient bone loss in the mice model. The results of in vitro experiment showed that CS-6 can inhibit RANKL-induced OC formation and the ability of bone resorption in a dose-dependent manner at both the early and late stages of osteoclastogenesis. The gene expression of OC-related key genes such as tartrate-resistant acid phosphatase (TRAP), CTSK, DC-STAMP, MMP9, and β3 integrin was evidently reduced. In addition, CS-6 could mitigate the systemic estrogen-dependent bone loss and pro-inframammary cytokines in mice in vivo. The molecular mechanism analysis suggested that CS-6 can suppress RANKL/TRAF6-induced early activation of NF-κB and ERK/MAPK signaling pathways, which consequently suppressed the transcription activity of c-Fos and NFATc1. Taken together, this present study provided ample evidence that CS-6 has the promise to become a therapeutic candidate in treating osteolytic conditions mediated by elevated OC formation and bone resorption.

The prevalence of ossification of the posterior longitudinal ligament (OPLL) is increasing, and currently there is no effective medical treatment for OPLL. Methyltransferase like 3 (METTL3), one of the components of the N6-methyladenosine (m6A) methyltransferase complex, regulates gene expression via modification of mRNA. Although METTL3 has been implicated in a variety of diseases, its role in OPLL remains to be elucidated. Primary ligament fibroblasts were used in this study. To investigate the role of METTL3 in OPLL, METTL3 was silenced or overexpressed. m6A RNA methylation was measured by commercially available kits. Luciferase reporter assay was performed to investigate the binding of miR-302a-3p and METTL3, and the binding of miR-302a-3p and USP8. Quantitative RT-PCR and western blots were used to evaluate mRNA and protein expression, respectively. OPLL increases METTL3 and its m6A modification. Overexpressing METTL3 significantly promoted osteogenic differentiation of primary ligament fibroblasts. Mechanism study showed that METTL3 increased m6A methylation of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST). Further study showed that lncRNA XIST regulates osteogenic differentiation of primary ligament fibroblasts via miR-302a-3p, which targets ubiquitin-specific protease 8 (USP8). METTL3 enhanced osteogenic differentiation of primary ligament fibroblasts via the lncRNA XIST/miR-302a-3p/USP8 axis. The findings highlight the importance of METTL3-mediated m6A methylation of XIST in OPLL and provide new insights into therapeutic strategies for OPLL.

The study of super-gentrification has important practical significance for maintaining social fairness, spatial justice and achieving sustainable urban development. In this article, 23 driving factors influencing super-gentrification are identified by literature research and Delphi method. Then, the 23 driving factors affecting super-gentrification are divided into four dimensions: political, economic, social and spatial dimension. On this basis, hypotheses are proposed and a structural equation model is established. Then, SPSS 25.0 and AMOS 24.0 software are used to test the reliability and validity of the questionnaire data, and the model results are fitted and modified. Finally, the optimization model and path coefficient of super-gentrification driving factors are calculated. The results of the study show that political factors, economic factors, social factors, and spatial factors, all play a positive role in the development of super-gentrification. Social factors are the fundamental factors to promote super-gentrification, political factors, economic factors, and spatial factors also play a key role in the super-gentrification process.

Urban rail transit can improve a city’s accessibility. However, high construction and operation costs restrict the development of urban rail transit. Value capture recoups the additional value that the investments of urban rail transit confer to local land and is considered to be an effective measure to alleviate this financial problem. Understanding the land value uplift effects of urban rail transit is essential for understanding value capture. This study applied a Space-P model of urban rail transit network based on complex network theory and demonstrated the influence of urban rail transit network characteristics on residential and commercial land prices. The model was tested with eight metropolises in China, using the 2003 to 2022 timeframe as the context. The results showed a significant positive correlation between the number of nodes and the land prices, the average clustering coefficient was highly positively correlated with the land prices, and there was a significant negative correlation between the average path length and the land prices. This study provides theoretical support for value capture, is beneficial for urban rail transit planning, and supports improvements in the development quality of urban rail transit networks.

Objective. This present study aimed to explore the clinical effects of a novel capsule lumbar interbody fusion (CLIF) on foot drop due to lumbar degenerative diseases. Methods. Between June 2018 and January 2019, a total of 27 patients admitted to our department with lumbar degenerative diseases with associated foot drop were prospectively enrolled. Given the selection of surgical technique, patients were divided into traditional TLIF group and CLIF group. We assessed patients’ neurological status using JOA and VAS score, tibialis anterior muscle strength using MMT score, diameter and hemodynamic parameters of the L5 nerve root using intraoperative ultrasonography (IoUS), and related radiological parameters of the lumbar spine. Operation time, blood loss, and surgery-associated complications were also recorded. Results. The median duration of follow-up was 150 (6–1460) months. At the final follow-up, all patients acquired satisfactory improvement of neurological function. However, patients in the CLIF group showed better early recovery of foot drop three months after operation than those in the TLIF group, with 75% excellent rate. In addition, IoUS suggested that the diameter and hemodynamic parameters of the L5 nerve root were improved better in the CLIF group, which may suggest the correlation between the recovery of foot drop and the status of L5 nerve root. No severe complications were encountered with CLIF. Conclusions. Our preliminary study revealed that the axial tension of L5 nerve root may be involved in the pathological mechanism of foot drop. The novel technique of CLIF can shorten the lumbar spine and can be effective and safe for the treatment of foot drop due to lumbar degeneration-related diseases.

Urban vitality is the primary driver of urban development. However, assessing urban vitality has always been a challenge. This paper builds on the research framework of sustainable development evaluation and selects evaluation indicators from the three systems of urban operation: economy, society, and environment. The deviation maximization (DM) method is used to evaluate urban vitality. Shanghai is then used as a case study for evaluation, and the comprehensive index of urban vitality is calculated for the city from 2010 to 2019. The evaluation results indicate that the urban vitality of Shanghai experienced a significant upward trend over ten years (2010–2019), which shows that the urban competitiveness of Shanghai is constantly strengthening. Next, the study focuses on the administrative region of Shanghai, to calculate the regional vitality level of Shanghai from 2010 to 2019 and to explore its spatial distribution characteristics. Then, a spatial autocorrelation analysis is used to explore the mechanism that affects the spatial distribution of urban vitality. The results demonstrate that the urban vitality in Shanghai shows a significant positive correlation in space. Moreover, there is a “High–High” gathering area, which includes Huangpu, Xuhui, Hongkou, and Changning in central area of Shanghai. This research provides a theoretical reference to support effective decision-making with respect to high-quality urban development.

Abstract It is a great challenge to prepare “functional artificial bone” for the repair of large segmental defect, especially in weight-bearing bones. In this study, bioactive HA/PCL composite scaffolds that possess anatomical structure as autogenous bone were fabricated by CT-guided fused deposition modeling technique. The scaffolds can provide mechanical support and possess osteoconduction property. Then the VEGF-165/BMP-2 loaded hydrogel was filled into biomimetic artificial bone spatially to introduce osteoinduction and angioinduction ability via sustained release of these cytokines. It has been revealed that the cytokine-loaded hydrogel possessed good biodegradability and could release the VEGF-165/BMP-2 sustainedly and steadily. The synergistic effect of these two cytokines showed significant stimulation on the osteogenic gene expresssion of osteoblast in vitro and ectopic ossification in vivo. The scaffolds were then implanted into the rabbit tibial defect sites (1.2 cm) for bone regeneration for 12 weeks, indicating the best repair of defect in vivo, which was superior to the pure hydrogel/scaffolds or one-cytokine loaded hydrogel/scaffolds and close to autogenous bone graft. The strategy to construct an “anatomy-structure-function” trinity system as functional artificial bone shows great potential in replacing autogenous bone graft and applying in large bone defect repair clinically in future.

Objectives: To retrospectively review the cases with ossification of the posterior longitudinal ligament (OPLL) treated with anterior controllable antedisplacement and fusion (ACAF). Patients with postoperative remaining ossification mass (PROM) are analyzed to figure out the causes and preventions of this problem. Methods: A total of 115 patients were included. PROM was identified as remaining OPLL existed in the spinal canal other than included in the vertebral-OPLL complex on postoperative computed tomography. The Japanese Orthopaedic Association scoring system was used to evaluate the neurologic status. Surgery-related complications such as cerebrospinal fluid (CSF) leakage and spinal cord or nerve injury were all recorded. The patients with the PROM group and those without the PROM group were compared. Results: There were 14 patients with wide-base OPLL (12.2%) and 10 patients (8.7%) with PROM among the 115 patients with OPLL. The 10 patients with PROM were all with wide-base OPLL. The average improvement rate of Japanese Orthopaedic Association score in patients without PROM was significantly larger than that in patients with PROM (69.5 ± 22.6% vs. 36.7 ± 22.0, P < 0.01). Incidence rate of postoperative CSF leakage and neural deterioration were significantly higher in patients with PROM than that in patients without PROM (CSF leakage, 40.0% vs. 5.9%; neural deterioration, 50.0% vs. 3.0%). No other complications were observed. Conclusions: The occurrence of PROM might cause complications and poor neural function recovery in patients treated with ACAF. Surgical techniques should be noted to avoid PROM in ACAF surgery. Key words: Anterior controllable antedisplacement and fusion, Complication, Ossification of the posterior longitudinal ligament, Postoperative remaining ossification mass, Wide-base OPLL

This paper conducts an analytical study on the urban-rural coordinated development (URCD) in the Yangtze River Delta urban agglomeration (YRDUA), and uses data from 2000–2015 of 27 central cities to study the spatial and temporal evolution patterns of URCD and to discover the influencing factors and driving forces behind it through PCA, ESDA and spatial regression models. It reveals that URCD of the YRDUA shows an obvious club convergence phenomenon during the research duration. The regions with high-level URCD gather mainly in the central part of the urban agglomeration, while the remaining regions mostly have low-level URCD, reflecting the regional aggregation phenomenon of spatial divergence. At the same time, we split URCD into efficiency and equity: urban-rural efficient development (URED) also exhibits similar spatiotemporal evolution patterns, but the patterns of urban-rural balanced development (URBD) show some variability. Finally, by analyzing the driving forces in major years during 2000–2015, it can be concluded that: (i) In recent years, influencing factors such as government financial input and consumption no longer play the main driving role. (ii) Influencing factors such as industrialization degree, fixed asset investment and foreign investment even limit URCD in some years. The above results also show that the government should redesign at the system level to give full play to the contributing factors depending on the actual state of development in different regions and promote the coordinated development of urban and rural areas. The results of this study show that the idea of measuring URCD from two dimensions of efficiency and equity is practical and feasible, and the spatial econometric model can reveal the spatial distribution heterogeneity and time evolution characteristics of regional development, which can provide useful insights for urban-rural integration development of other countries and regions.

In horizontal wells, the casing string is affected by the gravity effect, temperature effect, swelling effect, bending effect, friction effect and other mechanical effects. In view of this situation, the mathematical models of casing swelling effect and temperature effect caused by volume fracturing are established. The case analysis shows that the length of the unsealed section in the vertical section has a great influence on the axial shortening of the casing during fracturing. With the increase of the unsealed section length, the axial shortening of the casing increases gradually under the same wellhead pressure. In the process of fracturing, repeated squeezing and pressurization lead to periodic changes of the wellhead pressure, casing deformation and load, which leads to fatigue damage and even fracture of casing. At the same time, a large amount of fracturing fluid is continuously injected through the casing during the fracturing process, which makes the wellbore temperature change greatly. The additional stress caused by the temperature change reduces the casing strength, which has an important impact on the wellbore integrity. The mathematical model of temperature stress and its effect on the casing strength during volume fracturing is established. With the increase of the temperature stress acting on the casing, the casing collapse strength decreases gradually. When the temperature stress reaches 200 MPa, the casing collapse strength decreases to 84% of the original. The research results can provide a reference for the casing integrity design and control in the horizontal well fracturing process.

Background/Aims: Human bone marrow-derived mesenchymal stem cells (hMSCs) are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts. The bone morphogenetic protein-inducible gene homeobox a10 (HOXA10) is a critical regulator of osteogenesis. The objective of the present study was to identify microR-NAs (miRNAs) targeting HOXA10 and examine the effects on the osteogenic differentiation of hMSCs. Methods: Based on in silico analysis, HOXA10-targeting miRNAs were selected and their regulatory roles in osteoblast differentiation were investigated. Results: Six HOXA10-targeting miRNAs were identifIed by computational analysis, of which miR-320a was selected for further analysis because it was downregulated during osteogenic induction. Overexpression of miR-320a downregulated HOXA10 and significantly inhibited osteogenesis in hMSCs, as determined by the downregulation of the osteogenic markers Runx2, ALP, and OC and the inhibition of ALP activity and matrix mineralization, whereas miR-320a inhibition had the opposite effects. Furthermore, ectopic expression of HOXA10 (not including 3′-UTR) rescued the effects of miR-320a on osteogenic differentiation. Conclusion: These results suggest that miR-320a acts as a critical regulator of osteogenic differentiation of hMSCs by repressing its target HOXA10.

Aims: Connexin 43 is one of the most potent gap junction proteins related to osteoblast differentiation and bone formation. We hypothesized that Connexin 43 is a significant factor in osteogenic differentiation in the posterior longitudinal ligament through the regulation of extracellular signal-regulated kinases (ERK) activity by converging on Runt-related transcription factor 2 (Runx2) activity. In this study, we mapped the activity of Connexin 43 to ERK and Runx2 by extracting longitudinal ligament cell for culture and silencing Connexin expression in addition to dexamethasone treatment in vitro. Methods: qRT-PCR, Western Blot, and Runx2-responsive Luciferase Reporter Assay were performed to detect the activity of ERK, Runx2 and the expression levels of osseous genes under Connexin 43 modification. Results: Downregulation of Connexin 43 resulted in suppression of dexamethasone-induced osteogenic differentiation, inhibition of the ERK and Runx2 activity, and reduction of osseous gene expression. Conclusion: these data support that Connexin 43 significantly regulates osteogenic differentiation in the cells from posterior longitudinal ligament by altering the activity of ERK, and subsequently causing the modification of Runx2.

The driving force of super-gentrification shapes a complex system in which multiple dynamic factors interact with each other. This paper takes the dynamic factor system of super-gentrification as the research object and uses the Interpretative Structure Modeling (ISM) to analyze these dynamic factors. The levels of these dynamic factors and the interaction between them are determined. The Cross Impact Matrix Multiplication Applied to a Classification (MICMAC) analysis is also conducted to determine the dependence power and driving power of these dynamic factors. Through analysis, it is concluded that the dynamic factors of super-gentrification are distributed on six levels. Among these dynamic factors, Transformation of Industrial Structure and Occupational Structure in Urban Central Areas, Housing Needs of Overseas Elites, Investment Needs, Development of the Real Estate Market, and Unique Areas and Lifestyle Preferences are the fundamental dynamic factors affecting super-gentrification. The findings of this paper can enrich the existing theoretical research on the driving force of super-gentrification and can provide a reference for policy makers to promote urban landscape sustainability to some extent.

In the past few decades, a considerable number of old houses have been demolished in China’s urban redevelopment projects, which led to the disappearance of some historic buildings and the relocation of the original residents. Recently, the strategy of housing demolition (HD) in Chinese cities has been replaced by housing conservation and renovation (HCR). However, the transition from HD to HCR is not carried out well. This study aims to explore the key challenges in HCR practice by using a mixed method. Based on the field investigations in pilot projects and semistructured interviews, current HCR practices in Shanghai are summarized, and the four key challenges are identified as: (1) funding shortages; (2) an underdeveloped regulatory environment; (3) a psychological gap between the government and residents; and (4) a lack of stakeholders’ involvement. Targeted measures are proposed to mitigate the challenges. The findings and suggestions here could provide valuable references for the government when making decisions on sustainable housing conservation and renovation, and may promote urban renewal practices in China and other developing countries.

OBJECTIVE: The purpose of this study was to analyze the clinical features and prognostic factors of surgical outcome of foot drop caused by lumbar degenerative disease and put forward the clinical stage. METHODS: We retrospectively reviewed 135 patients with foot drop due to lumbar degenerative disease. The clinical features and mechanism were analyzed. Age, sex, duration of palsy, preoperative muscle strength of tibialis anterior (TA), sensation defect of affected lower limb, affected foot, diagnosis and compressed nerve roots were recorded and compared with surgical outcome. RESULTS: Foot drop was observed in 8.1% of all inpatients of lumbar degenerative disease. L5 nerve root compression was observed in 126 of all 135 patients (93.3%). Single, double and triple roots compression was observed respectively in 43, 83, and 9 patients (31.9%, 61.5%, and 6.6%). But there was no significant relationship between preoperative muscle strength of TA and the number of compressed roots. The muscle strength of TA was improved in 113 (83.7%) patients after surgery, but it reached to >=4 in only 21 (15.6%) patients. Improvement of the muscle strength of TA was almost stable at the 6-month follow-up. At the last follow-up, the muscle strength of TA was 1, 2, 3, 4, 5 respectively in 28, 24, 62, 13, 8 patients. Multivariate logistic regression showed duration of palsy (p=0.0360, OR=2.543), preoperative muscle strength of TA (p=0.0064, OR=5.528) and age (p=0.0309, OR=3.208) were factors that influenced recovery following an operation. CONCLUSIONS: L5 nerve root was most frequently affected. The muscle strength of TA improved in most patients after surgery, but few patients can get a good recovery from foot drop. Patients of shorter duration of palsy, better preoperative muscle strength of TA and younger age showed a better surgical outcome.

BACKGROUND: Many observational studies assessed the association between obesity and risk of hip fracture in adults, but reported controversial results. Our goal was to evaluate the association between obesity and risk of hip fracture in adults by conducting a meta-analysis of prospective cohort studies. METHODS: Three databases, PubMed, Embase and Web of Science, were searched through May 2012 to identify eligible cohort studies. Either a fixed- or a random-effects model was used to calculate the pooled relative risk (RR) with its 95% confidence interval (95%CI). RESULTS: Fifteen prospective cohort studies involving a total 3,126,313 participants were finally included into this meta-analysis. Overall, adults with obesity compared with the normal weight group had a significantly decreased risk of hip fracture (RR: 0.66, 95% CI 0.57 to 0.77, P

BACKGROUND: Neuropathic intermittent claudication (NIC) is a typical clinical symptom of lumbar spinal stenosis and the apoptosis of neurons caused by cauda equina compression (CEC) has been proposed as an important reason. Whereas, the factors and the mechanism involved in the process of apoptosis induced by CEC remain unclear. METHODOLOGY AND RESULTS: In our modified rat model of NIC, a trapezoid-shaped silicon rubber was inserted into the epidural space under the L5 and L6 vertebral plate. Obvious apoptosis was observed in spinal cord cells after compression by TUNEL assay. Simultaneously, qRT-PCR and immunohistochemistry showed that the expression levels of PUMA (p53 up-regulated modulator of apoptosis) and p53 were upregulated significantly in spinal cord under compression, while the expression of p53 inhibitor MDM2 and SirT2 decreased in the same region. Furthermore, CEC also resulted in the upregulation of Bcl-2 pro-apoptotic genes expression and caspase-3 activation. With the protection of Methylprednisolone, the upregulation of PUMA and p53 expression as well as the decrease of MDM2 and SirT2 in spinal cord were partially rescued in western bolt analysis. CONCLUSIONS: These results suggest that over-expression of PUMA correlates with CEC caused apoptosis of spinal cord cells, which is characterized by the increase of p53, Bax and Bad expression. PUMA upregulation might be crucial to induce apoptosis of spinal cord cells through p53-dependent pathway in CEC.