A role of prefrontal cortico-hypothalamic projections in wake promotion.

Ventromedial prefrontal cortex (vmPFC) processes many critical brain functions, such as decision-making, value-coding, thinking, and emotional arousal/recognition, but whether vmPFC plays a role in sleep-wake promotion circuitry is still unclear. Here, we find that photoactivation of dorsomedial hypothalamus (DMH)-projecting vmPFC neurons, their terminals, or their postsynaptic DMH neurons rapidly switches non-rapid eye movement (NREM) but not rapid eye movement sleep to wakefulness, which is blocked by photoinhibition of DMH outputs in lateral hypothalamus (LHs). Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFC promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMH produces opposite effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Thus, vmPFC neurons innervating DMH likely represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep.

Characterization of myeloid signature genes for predicting prognosis and immune landscape in Ewing sarcoma.

Myeloid cells as a highly heterogeneous subpopulation of the tumor microenvironment (TME) are intimately associated with tumor development. Ewing sarcoma (EWS) is characterized by abundant myeloid cell infiltration in the TME. However, the correlation between myeloid signature genes (MSGs) and the prognosis of EWS patients was unclear. In this research, we synthetically characterized the expression of MSGs in a training cohort and classified EWS patients into two subtypes. Immune cell infiltration analysis revealed that MSGs subtypes correlated closely with different immune statuses. Furthermore, a three-gene prognostic model (CTSD, SIRPA, and FN1) was constructed by univariate, LASSO, and multivariate Cox analysis, and it showed excellent prognostic accuracy in EWS patients. We also developed a nomogram for better predicting the long-term survival of EWS. Functional enrichment analysis showed immune-related pathways were distinctly different in the high- and low-risk groups. Further analysis revealed that patients in the high-risk group were tightly associated with an immunosuppressive microenvironment. Finally, we validated the expression of these candidate genes by Western blot (WB), qPCR, and immunohistochemistry (IHC) analysis. To sum up, our study identified that the MSGs model was strongly linked to prognostic prediction and immune infiltration in EWS patients, providing novel insights into the clinical treatment and management of EWS patients.

Blood transcriptome and machine learning identified the crosstalk between COVID-19 and fibromyalgia: a preliminary study.

OBJECTIVES: The COVID-19 pandemic caused by SARS-CoV-2 has seriously threatened the human health. Growing evidence shows that COVID-19 patients who recovery will persist with symptoms of fibromyalgia (FM). However, the common molecular mechanism between COVID-19 and FM remains unclear. METHODS: We obtained blood transcriptome data of COVID-19 (GSE177477) and FM (GSE67311) patients from GEO database, respectively. Subsequently, we applied Limma, GSEA, Wikipathway, KEGG, GO, and machine learning analysis to confirm the common pathogenesis between COVID-19 and FM, and screened key genes for the diagnosis of COVID-19 related FM. RESULTS: A total of 2505 differentially expressed genes (DEGs) were identified in the FM dataset. Functional enrichment analysis revealed that the occurrence of FM was intimately associated with viral infection. Moreover, WGCNA analysis identified 243 genes firmly associated with the pathological process of COVID-19. Subsequently, 50 common genes were screened between COVID-19 and FM, and functional enrichment analysis of these common genes primarily involved in immunerelated pathways. Among these common genes, 3 key genes were recognised by machine learning for the diagnosis of COVID-19 related FM. We also developed a diagnostic nomogram to predict the risk of FM occurrence which showed excellent predictive performance. Finally, we found that these 3 key genes were closely relevant to immune cells and screened potential drugs that interacted with the key genes. CONCLUSIONS: Our study revealed the bridge role of immune dysregulation between COVID-19 and fibromyalgia, and screened underlying biomarkers to provide new clues for further clinical research.

Preoperative prediction of sagittal imbalance in kyphosis secondary to ankylosing spondylitis after one-level three-column osteotomy.

BACKGROUND: This study aimed to determine preoperative predictors for sagittal imbalance in kyphosis secondary to ankylosing spondylitis (AS) after one-level three-column osteotomy. METHODS: A total of 55 patients with AS who underwent one-level three-column osteotomy were enrolled. The patients were divided into two groups according to sagittal vertical axis (SVA) value at the final follow-up (group A: SVA > 5 cm; group B: SVA ≤ 5 cm). The radiographic measures included global kyphosis, lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope, T1 pelvic angle (TPA), SVA, osteotomized vertebral angle and PI and LL mismatch (PI - LL). Postoperative clinical outcomes were evaluated using Scoliosis Research Society-22 questionnaire (SRS-22) and Oswestry Disability Index (ODI). RESULTS: Fifty-five AS patients had an average follow-up of 30.6 ± 10.2 months (range 24-84 months). Group A had larger preoperative and postoperative LL, PT, PI - LL, TPA and SVA values compared with group B (P < 0.05), and no significant differences were found in ODI and SRS-22 scores between the two groups (P > 0.05). Preoperative LL, PT, PI - LL, TPA, and SVA values were positively correlated with the follow-up SVA value (P < 0.05). Among them, TPA > 40.9°, PI - LL > 32.5° and SVA > 13.7 cm were the top three predictors with the best accuracy to predict sagittal imbalance. Immediate postoperative SVA value of ≤ 7.4 cm was a key factor in reducing the risk of sagittal imbalance during follow-up. CONCLUSIONS: Preoperative TPA > 40.9°, PI - LL > 32.5° and SVA > 13.7 cm could predict sagittal imbalance in AS kyphosis after one-level three-column osteotomy, and additional osteotomies were recommended for this condition. Immediate postoperative SVA ≤ 7.4 cm was an optimal indicator for preventing sagittal imbalance. LEVEL OF EVIDENCE: IV.

The twisted structure of the rat Achilles tendon.

The rat is frequently used as a model to study the characteristics, aetiology and pathology of the Achilles tendon. However, though the structure of the human Achilles tendon has been extensively investigated, the anatomical structure of the rat Achilles tendon remains unclear, which impedes the ability to use rats to study Achilles tendinopathy. The purpose of this study was to reveal the structure of the rat Achilles tendon and to explore its similarities with the human Achilles tendon through an anatomical dissection of 80 rat Achilles tendons (40 female, 40 male). This study found that the subtendons of the rat Achilles tendon originating from the triceps surae muscle were twisted, and each subtendon also had its own torsion. The extent of these two types of torsion could be very different between rats. Alterations in this torsion may result in distinct stress fields in the Achilles tendon, which may play a critical role in the pathogenesis of Achilles tendinopathy. This study provides an important basis to support the use of rats as model animals to investigate the characteristics of the human Achilles tendon and Achilles tendinopathy.

Retracted: Modified Closing-Opening Wedge Osteotomy to Correct Kyphosis in Ankylosing Spondylitis.

An Editorial decision has been made to retract the manuscript, Feng C, et al. Modified Closing-Opening Wedge Osteotomy to Correct Kyphosis in Ankylosing Spondylitis. Med Sci Monit. 2019; 25:6532-6538. It has come to our attention that the method of modified closing opening wedge osteotomy is not an original procedure developed by the authors, but has previously been described by Boissière L, et al. Spine J. 2015;15(12):2574-82, and Gao R, et al. Spine J. 2015;15(9):2009-15, and Boachie-Adjei O, et al. Spine (Phila Pa 1976). 2006;31(4):485-92.

Modified Closing-Opening Wedge Osteotomy to Correct Kyphosis in Ankylosing Spondylitis.

BACKGROUND The aim of this study was to analyze the clinical and radiological outcomes of modified closing-opening wedge osteotomy (mCOWO) for correcting kyphosis in ankylosing spondylitis (AS) patients. MATERIAL AND METHODS From April 2012 to April 2017, records of consecutive patients who underwent mCOWO were reviewed. The clinical and radiological outcomes were analyzed preoperatively, postoperatively, and at the most recent follow-up. RESULTS Eleven AS patients underwent mCOWO, with a mean follow-up of 19.4 months (range, 12-45 months). The average sagittal vertical axis (SVA) was corrected from 191.9 mm preoperatively to 75.9 mm postoperatively (P<0.05) and 78.9 mm at the most recent follow-up (P<0.05). The average correction angles at the osteotomy site were 44.5° postoperatively and 45.0° at the most recent follow-up (P>0.05). Sagittal translation (ST) occurred in 2 patients, and 5 mm was the maximum. There was no neurologic damage. Solid fusion was observed at the most recent follow-up in all patients. CONCLUSIONS Modified closing-opening wedge osteotomy (mCOWO) is an effective technique for correcting kyphosis in patients with AS.

Is It Possible to Correct Congenital Spinal Deformity Associated With a Tethered Cord Without Prophylactic Intradural Detethering?

BACKGROUND: Patients who have a congenital spinal deformity with a tethered cord generally are treated with prophylactic intradural detethering before deformity correction. However, the detethering procedure carries substantial risk, and it is not clear whether deformity correction can be performed without detethering. QUESTIONS/PURPOSES: To determine the (1) correction rate, (2) proportion of patients who experienced complications after surgery, and (3) neurological status after recovery from surgery in a group of patients with congenital spinal deformity and a tethered cord who were treated either with posterior spinal fusion only (PSF), pedicle-subtraction osteotomy (PSO), or a vertebral column resection (VCR), based on an algorithmic approach. METHODS: Between 2006 and 2016, we treated 50 patients surgically for a congenital spinal deformity and a tethered cord. We defined a congenital spinal deformity as one that was caused by failure of vertebral segmentation, failure of vertebral formation, or both, and we made the diagnosis of a tethered cord based on a conus medullaris lower than L2 level, or a diameter of the filum terminale greater than 2 mm, as shown on magnetic resonance image. Of those, nine patients were lost to followup before the 2-year minimum, leaving 41 for analysis at a mean followup of 47 months (range, 24 to 92 months) in this single-institution retrospective study. The treatment algorithm involved one of three approaches: PSF, PSO, or VCR. A total of 15 patients underwent PSF; we used this approach for patients with moderate curves (Cobb angle < 80°) and intact neurological status both previously and during a bending and traction test. Eleven patients underwent PSO; we performed PSO when patients had neurological symptoms (in daily life or during the traction/bending test) and a magnitude of the curve less than 80°. Finally, 15 patients underwent VCR, which we used in patients with a magnitude of the curve more than 80° and/or flexibility less than 20%, with/without neurological symptoms. No patient in any group underwent intradural detethering. We report on the correction rate, defined as the ratio between the corrected magnitude and preoperative magnitude of a curve at a given postoperative time point (correction rate = 1- (Cobb angle at a given time point/preoperative Cobb angle) x 100%); complications, that is, postoperative/recurrent neurological symptoms, cerebrospinal fluid leakage, infection, blood loss > 5000 mL, as determined by chart review performed by an individual not directly involved in patient care; and a detailed neurological exam, including evaluations of sensory function, extremity muscle strength, pain, gait, physiological reflexes, and pathological signs, both before surgery and at most recent followup, as performed by the surgeon. All neurologically symptomatic patients were evaluated with a neurologic scoring system. RESULTS: The overall mean ± SD correction rate in this series was 63% ± 14%. It was 70% ± 12% in the PSF group, 64% ± 17% in the PSO group, and 56% ± 12% in the VCR group. Seven patients in those three groups experienced major complications, including blood loss more than 5000 mL, temporary neurological symptoms, cerebrospinal fluid leakage, and infection. The most severe complications included one patient in the VCR group who had temporarily decreased strength in the lower limb, and one patient in the PSO group with temporary numbness in the lower limb. Finally, no patients in PSF group had postoperative neurological complications, and all patients with neurological symptoms in the PSO/VCR group improved to varying degrees. For neurologically symptomatic patients in PSO group (n = 6), the neurological score improved slightly, from 22.5 ± 1.9 preoperatively to 24.2 ± 0.8 at the most recent followup (p = 0.024) with a mean difference of 1.7. For neurologically symptomatic patients in VCR group (n = 10), the neurological score improved slightly from 23.1 ± 1.1 preoperatively to 24.2 ± 0.6 at most recent followup (p = 0.009) with a mean difference of 1.1. CONCLUSIONS: Congenital spinal deformity with a tethered cord may be treated without prophylactic intradural detethering. In the current series treated according to this treatment algorithm, good correction and neurological improvement were achieved, and few complications occurred. However, such a small series cannot prove the safety of this treatment; for that, larger, multicenter studies are necessary. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Surgical management of sacral meningeal cysts by obstructing the communicating holes with muscle graft.

BACKGROUND: The surgical indication and treatment of sacral meningeal cyst have not been well established and current methods are usually accompanied by complications and recurrence. The aim of this study is to discuss the treatment of symptomatic sacral meningeal cyst, by investigating the surgical results of our surgically treated patients, and minimize the complications and recurrence. METHODS: We retrospectively reviewed all patients with symptomatic sacral meningeal cysts who were surgically treated by a single surgeon in the same institution from 2002 to 2017. All patients underwent the same operation by incising the cyst wall and obstructing the communicating hole with muscle graft, while the cyst wall was left untreated instead of resected or imbricated. The obstruction was verified by doing a Valsalva-like maneuver. The preoperative symptoms and signs, and the outcomes at most recent follow-up were rated and compared by Neurological Scoring System. RESULTS: A total of 18 patients (7 male patients and 11 female patients, average age 42.3 years) were followed up for an average of 51.7 months. All patients had communicating holes linking the cysts and the dural sacs. The average preoperative neurological score was 19.7 ± 2.2, and it was improved to 23.2 ± 2.8 at the most recent follow-up (p < 0.01). CONCLUSIONS: The sacral meningeal cyst originated from the communication with the dural sac. Surgical treatment of symptomatic sacral meningeal cysts can yield a long-term resolution of the appropriately selected patient's symptoms. Obstructing the communicating hole with muscle graft is an effective and simple method to obliterate the cyst. The incised cyst wall can be left untreated instead of resected or imbricated.

A new vaccine targeting RANKL, prepared by incorporation of an unnatural Amino acid into RANKL, prevents OVX-induced bone loss in mice.

Bone homeostasis is maintained by a dynamic balance between osteoblastic bone formation and osteoclastic bone resorption. The receptor activator of nuclear-κB ligand (RANKL) is essential for the function of the bone-resorbing osteoclasts, and targeting RANKL has been proved highly successful in osteoporosis patients. This study aimed to design a novel vaccine targeting RANKL and evaluate its therapeutic effects in OVX-induced bone loss model. Anti-RANKL vaccine was generated by incorporating the unnatural amino acid p-nitrophenylalanine (pNO2Phe) into selected sites in the murine RANKL (mRANKL) molecule. Specifically, mutation of a single tyrosine residue Tyr234 (Y234) or Tyr240 (Y240) of mRANKL to pNO2Phe (thereafter named as Y234pNO2Phe or Y240pNO2Phe) induced a high titer antibody response in mice, whereas no significant antibody response was observed for the wild type mRANKL (WT mRANKL). The antiserum induced by Y234pNO2Phe or Y240pNO2Phe could efficiently prevent osteoclastogenesis in vitro. Moreover, immunization with Y234pNO2Phe or Y240pNO2Phe could also prevent OVX-induced bone loss in mice, suggesting that selected pNO2Phe-substituted mRANKL may pave the way for creating a novel vaccine to treat osteoporosis.

Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway.

Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 µmol/L) or the caspase inhibitor Z-VAD-fmk (20 µmol/L) followed by treatment with VK2 (10 µmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days. Calcium deposition was determined by the o-cresolphthalein complexone assay and Alizarin Red S staining. Apoptosis was determined by TUNEL and flow cytometry using Annexin V-FITC and propidium iodide staining. Western blotting detected the expressions of Axl, Gas6, p-Akt, Akt, and Bcl2. VK2 significantly inhibited CaCl2- and ß-sodium glycerophosphate (ß-GP)-induced VSMC calcification and apoptosis, which was dependent on restored Gas6 expression and activated downstream signaling by Axl, p-Akt, and Bcl2. Z-VAD-fmk significantly inhibited CaCl2- and ß-GP-induced VSMC calcification and apoptosis. Augmented recombinant mouse Gas6 protein (rmGas6) expression significantly reduced VSMC calcification and apoptosis. Furthermore, the Gas6/Axl interaction was inhibited by R428, which abolished the preventive effect of VK2 on CaCl2- and ß-GP-induced apoptosis and calcification. These results suggest that Gas6 is critical in VK2-mediated functions that attenuate CaCl2- and ß-GP-induced VSMC calcification by blocking apoptosis.

Neurological complications of thoracic posterior vertebral column resection for severe congenital spinal deformities.

PURPOSE: The risk of neurological injury during vertebral column resection is high. In this study, we investigated the incidence and risk factors for neurological complications when treating spinal deformities by thoracic posterior vertebral column resection (PVCR). METHODS: Between 2008 and 2013, there were 62 consecutive patients (34 female patients and 28 male; the mean age: 16.3 years, range 6-46 years) treated with thoracic PVCR. We retrospectively reviewed the clinical records to obtain demographic and radiographic data, operative time, estimated blood loss (EBL, the ratio between circulating and lost blood), bleeding volume (the lost blood), number of vertebrae fused, number of vertebrae resected, usage of titanium mesh cage, and intraoperative neuromonitoring data. Multi-factor logistic regression was used to find the major risk factors for neurological complications. RESULTS: The average follow-up period was 46 months (range 24-88 months); no patients were lost to follow up. The average operative time was 524.8 ± 156.8 min (range 165.0-880.0 min), the average bleeding volume was 2585 ± 2210 ml (100-9600 ml), and the average estimated blood loss was 75.8% (9-278%). Ten patients (16.1%) developed post-operative neurological complications (nine transient and one permanent). Multi-factor logistic regression revealed that the risk factors for neurological complications were age ≥18 years, pulmonary dysfunction, and EBL >50%. CONCLUSIONS: Thoracic PVCR can lead to satisfactory outcomes in the treatment of severe spinal deformities. Risk factors for neurological complications include the age over 18 years, presence of pulmonary dysfunction, and EBL greater than 50%. The pulmonary dysfunction can be regarded as the most valuable indicator to measure the severity of the spine deformity.

[Neurological complications of posterior vertebral column resection for severe rigid congenital spinal deformities].

OBJECTIVE: To analyze the risk factors of neurological complications of posterior vertebral column resection in the treatment of severe rigid congenital spinal deformities. METHODS: The clinical data of 88 patients with severe rigid congenital spinal deformities who underwent PVCR in Department Of Orthopaedics, Xijing Hospital, Fourth Military Medical University from June 2007 to November 2012 were collected. There were 39 males and 49 females at the average age of 16.9 years (range 6-46 years). To measure the Cobb angle and balance at preoperative, postoperative and follow up, and to record the operation report, neurological complications and at follow up. The relevant factors of neurological complications were analyzed by one-way analysis, including: age, Cobb angle, operation time, body mass index, pulmonary function, blood volume loss, resection level, number of vertebrae fixed, number of vertebrae resected, usage of cage or titanium mesh, preoperative neurologic function, the type of deformity and combination of spinal canal deformity, and further analyzed by multiariable Logistic regression analysis. RESULTS: The average follow up was 42 months (range 19 to 83 months). The number of resected vertebrae average 1.3 (range 1 to 3), operative time average 502.4 min (range 165.0 to 880.0 min), estimate blood loss average 2,238 ml (range 100 to 11,500 ml) for an average 69.3% blood volume loss (range 9% to 299%). The average preoperative major coronal curve of 93.6° corrected to 22.2°, at the final follow-up, the coronal curve was 22.2° with a correction of 76.8%. The average preoperative coronal imbalance (absolute value) was 2.5 cm decreasing to 1.3 cm at the final follow-up. The average preoperative major sagittal curve of 88.2° corrected to 28.7°, at the final follow-up, the sagittal curve was 29.2°, average decrease in kyphosis of 59.0°. The average preoperative sagittal imbalance (absolute value) was 3.1 cm decreasing to 1.2 cm at the final follow-up. There were 12 patients (13.6%) developed a neurological complications. High rate of neurological complications was occurred in patients with operative time greater than 480 min, pulmonary dysfunction, blood volume loss greater than 50%, T7-T99 osteotomy and preoperative neurologic compromise (P=0.046, 0.000, 0.000, 0.033, 0.043). CONCLUSIONS: Posterior vertebral column resection can achieve satisfactory efficacy in treatment of severe spinal deformities. Pulmonary dysfunction and blood volume loss greater than 50% were significant risk factors of neurological complications.

[One stage surgical treatment of congenital scoliosis associated with split cord malformation].

OBJECTIVE: To investigate the clinical results of one stage surgical treatment in congenital scoliosis (CS) patients associated with split cord malformation (SCM). METHODS: Between January 2007 and December 2010, 50 patients underwent one stage surgical treatment for CS associated with SCM. Among of them, 38 patients (13 male and 25 female) with an average age of (15 ± 6) years, who were followed up in the clinic at least 2 years longer, were include in the study. There were 12 patients with Type I SCM and 26 patients with Type II SCM Pre-operative, post-operative and the follow-up imaging data were collected and compared by paired t-test, while imaging data between Type I SCM group and Type II SCM group were compared by group t-test. Bony spur was first resected to the Type I SCM while nothing was done to the Type II SCM. Then, all patients were followed by posterior corrective procedure in one stage. Meanwhile, duraplasty were only applied in 5 patients whose dural cleft were more than 1 cm longer. RESULTS: The average follow-up was 41 ± 13 months (range, 26-68 months). The average operation time was 491 ± 152 minutes (range, 105-780 minutes) and the average blood loss was (1 933 ± 1 516) ml (range, 1 000-8 000 ml). The mean major coronal curve was corrected from 70° ± 26° preoperatively to 312° ± 16° postoperatively with a correction rate of 57% ± 18%, and 33° ± 17° at the final follow-up with a correction rate of 54% ± 20%. The mean major sagittal curve was corrected from 43° ± 31° to 26° ± 16°, and 27° ± 15° at the final follow-up. The postoperative complication occurred in 2 patients (5.3%) with Type I SCM, including neurological deterioration in 1 patient (2.6%) and cerebrospinal fluid leakage in 1 patient (2.6%). There were no paralysis and other serious complications. The patients who suffered from neurological deterioration recovered to the preoperative neurological status at 30 months postoperatively and no further improvement at the final follow-up. CONCLUSION: It is safe and efficient to treat the CS associated with SCM by one stage surgery without increasing the risk of neurological complications postoperatively.

Non-fusion and growing instrumentation in the correction of congenital spinal deformity associated with split spinal cord malformation: an early follow-up outcome.

STUDY DESIGN: A retrospective case review. INTRODUCTION: To evaluate the safety and efficacy of the non-fusion technique in achieving and maintaining the proper correction for congenital spinal deformity (CSD) and allowing normal spinal growth in patients with split spinal cord malformation (SSCM). MATERIALS AND METHODS: Seven patients who had CSD and SSCM were adopted, with a mean age of 8 years. All the patients in this study received Halo-gravity traction (HGT) prior to expansion of the spine and instrumentation with vertical expandable titanium prosthetic rib, growing rod or their hybrid. Five of them underwent opening wedge thoracoplasty simultaneously. And the two patients with type I SSCM underwent bony spur excision in the initial surgery before corrective manipulation. Then all the patients received a lengthened operation every six months. Changes of their major curve and length of T1-S1 spine were measured, and complications, neurological status were recorded. All the patients were followed up with an average of 32.6 months. RESULTS: Their mean major curve improved from 90.1° to 58.6° with a correction rate of 34.9 %. The T1-S1 length increased from 26.3 to 34.7 cm at final follow-up. Especially, one of the type I SSCM patients whose neurological deterioration was found preoperatively was significantly improved. CONCLUSION: Preoperative Halo-gravity traction followed by non-fusion and growing instrumentation may be effective and safe for young children of CSD associated with SSCM. But it is an ongoing study and additional large multicenter studies are necessary to further assess the safety and efficacy of non-fusion and growing instrumentation.

Staged corrective surgery for complex adolescent kyphoscoliosis caused by back scalding during the childhood period.

INTRODUCTION: Adolescent scar contracture kyphoscoliosis is a very rare disease. METHODS AND RESULTS: Here, we present the case of a 21-year-old man who was scalded due to ebullient water when he was 10 years old. Moreover, kyphoscoliosis was found when he was 12 years old and developed rapidly. Thereafter, no management was proposed before his consultation at our center. On examination, kyphoscoliosis was detected in thoracolumbar, the trunk deviated to the right on standing view, extensive contractured scar presented on the right side of the back, abdomen, chest wall, hip, right thighs and armpit anterior, especially in the right flank. A one-stage correction was deemed too risky, we therefore released contractured scar during the first stage with the defect of soft tissue protected by vacuum sealing drainage and then performed skeletal traction with halo and bilateral femoral pins. A reasonable correction was achieved without any neurological deficits 1 month after traction. Next, a second-stage operation was taken to translate a free anterolateral thigh myocutaneous flap to overlay the extensive defect of soft tissue. 1.5 months later, a third posterior segmental pedicle screw instrumented fusion with Smith-Peterson osteotomy between T9 and L2 was performed. Postoperative recovery was uneventful and as there were no complications, he was discharged 10 days after the third surgery. At 2-year follow-up the patient's outcome is excellent with balance and correction of the deformity. CONCLUSION: Based this grand round case and relevant literature, we discuss the different options for the treatment of adolescent scar contracture scoliosis.

Semi-XctNet: Volumetric images reconstruction network from a single projection image via semi-supervised learning.

Deep learning networks have achieved remarkable progress in various tasks of medical imaging. Most of the recent success in computer vision highly depend on large amounts of carefully annotated data, whereas labelling is arduous, time-consuming and in need of expertise. In this paper, a semi-supervised learning method, Semi-XctNet, is proposed for volumetric images reconstruction from a single X-ray image. In our framework, the effect of regularization on pixel-level prediction is enhanced by introducing a transformation consistent strategy into the model. Furthermore, a multi-stage training strategy is designed to ameliorate the generalization performance of the teacher network. An assistant module is also introduced to improve the pixel quality of pseudo-labels, thereby further improving the reconstruction accuracy of the semi-supervised model. The semi-supervised method proposed in this paper has been extensively validated on the LIDC-IDRI lung cancer detection public data set. Quantitative results show that SSIM (structural similarity measurement) and PSNR (peak signal noise ratio) are 0.8384 and 28.7344 respectively. Compared with the state-of-the-arts, Semi-XctNet exhibits excellent reconstruction performance, thus demonstrating the effectiveness of our method on the task of volumetric images reconstruction network from a single X-ray image.

Comprehensive landscape of immune-based classifier related to early diagnosis and macrophage M1 in spinal cord injury.

Numerous studies have documented that immune responses are crucial in the pathophysiology of spinal cord injury (SCI). Our study aimed to uncover the function of immune-related genes (IRGs) in SCI. Here, we comprehensively evaluated the transcriptome data of SCI and healthy controls (HC) obtained from the GEO Database integrating bioinformatics and experiments. First, a total of 2067 DEGs were identified between the SCI and HC groups. Functional enrichment analysis revealed substantial immune-related pathways and functions that were abnormally activated in the SCI group. Immune analysis revealed that myeloid immune cells were predominantly upregulated in SCI patients, while a large number of lymphoid immune cells were dramatically downregulated. Subsequently, 51 major IRGs were screened as key genes involved in SCI based on the intersection of the results of WGCNA analysis, DEGs, and IRGs. Based on the expression profiles of these genes, two distinct immune modulation patterns were recognized exhibiting opposite immune characteristics. Moreover, 2 core IRGs (FCER1G and NFATC2) were determined to accurately predict the occurrence of SCI via machine learning. qPCR analysis was used to validate the expression of core IRGs in an external independent cohort. Finally, the expression of these core IRGs was validated by sequencing, WB, and IF analysis in vivo. We found that these two core IRGs were closely associated with immune cells and verified the co-localization of FCER1G with macrophage M1 via IF analysis. Our study revealed the key role of immune-related genes in SCI and contributed to a fresh perspective for early diagnosis and treatment of SCI.

Anoikis patterns exhibit distinct prognostic and immune landscapes in Osteosarcoma.

OBJECTIVES: Osteosarcoma is highly aggressive and prone to metastasis, with a poor prognosis. Increasing evidence identified anoikis has a critical effect in tumor metastasis and invasion. However, the prognostic value of anoikis-related genes (ANRGs) in osteosarcoma and their role in the immune landscape of osteosarcoma remain unclear. METHODS: The RNA sequencing and clinical data of patients with osteosarcoma were extracted from the TARGET and GEO databases, and ANRGs were identified from the GeneCards database. Unsupervised clustering analysis was employed to identify anoikis-related patterns. The ESTIMATE, TIMER and ssGSEA algorithms were used to assess the immune microenvironment of different subtypes. A prognostic signature based on the identified ANRGs was constructed via univariate, LASSO and multivariate Cox regression analyses. KEGG, GO and GSEA were used for functional enrichment of genes associated with different risk subtypes. qPCR, WB and IHC were used to validate the expression of candidate genes. RESULTS: Two anoikis-related patterns with distinct clinical features and immune statuses were identified based on prognosis-related ANRGs. Cluster 2 had more active immunogenicity and a better prognosis than Cluster 1. Subsequently, we developed and validated an anoikis prognostic signature demonstrating excellent predictive ability for the prognosis of osteosarcoma. Anoikis risk score was positively associated with osteosarcoma metastasis and was identified as an independent prognostic marker. Additionally, a nomogram was established to predict the 3- and 5-year survival probability of patients with osteosarcoma. Functional enrichment analysis revealed that immune dysregulation was correlated with poor prognosis. Besides, patients in the low-risk group had higher infiltration levels of immune cells and more active immune function than patients in the high-risk group. Drug sensitivity analysis revealed several chemotherapeutic agents for the treatment of different subtypes of osteosarcoma. CONCLUSION: Our study demonstrated the role of ANRGs in osteosarcoma progression, providing insights into clinical decision making in osteosarcoma.

Recent Strategies to Combat Biofilms Using Antimicrobial Agents and Therapeutic Approaches.

Biofilms are intricate bacterial assemblages that attach to diverse surfaces using an extracellular polymeric substance that protects them from the host immune system and conventional antibiotics. Biofilms cause chronic infections that result in millions of deaths around the world every year. Since the antibiotic tolerance mechanism in biofilm is different than that of the planktonic cells due to its multicellular structure, the currently available antibiotics are inadequate to treat biofilm-associated infections which have led to an immense need to find newer treatment options. Over the years, various novel antibiofilm compounds able to fight biofilms have been discovered. In this review, we have focused on the recent and intensively researched therapeutic techniques and antibiofilm agents used for biofilm treatment and grouped them according to their type and mode of action. We also discuss some therapeutic approaches that have the potential for future advancement.