Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Association of abnormal NDUFB2 and UQCRH expression with venous thromboembolism in patients with liver cirrhosis.

Venous thromboembolism (VTE) refers to abnormal coagulation of blood in veins, resulting in complete or incomplete occlusion of the blood vessels. Patients with liver cirrhosis are prone to blood clots. However, relationship between NDUFB2 and UQCRH and VTE is not clear. GSE19151 and GSE48000 profiles for venous thromboembolism were downloaded from gene expression omnibus (GEO) generated using GPL571 and GPL10558. Multiple datasets were merged and batched. The differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. The construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, Gene Set Enrichment Analysis (GSEA) were conducted. Gene expression heat map was drawn. Comparative toxicogenomics database (CTD) analysis were performed to find disease most related to the core genes. Western blotting (WB) experiments were further verified. TargetScan screened miRNAs that regulated central DEGs. 129 DEGs were identified. According to gene ontology (GO), DEGs were mainly enriched in mRNA metabolism, oxidative phosphorylation, nucleic acid binding and enzyme binding. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis showed that target cells were mainly enriched in ribosomes and oxidative phosphorylation. The intersection of enrichment items and GOKEGG enrichment items of DEGs is mainly enriched in oxidative phosphorylation, myocardial contraction and ribosome. In the metascape enrichment project, dna template transcription, cell stress response regulation and proton transport across the membrane can be seen in the GO enrichment project. The PPI network obtained 10 core genes (COX7C, NDUFB2, ATP5O, NDUFA4, NDUFAB1, ATP5C1, ATP5L, NDUFA7, NDUFA6, UQCRH). Gene expression heat map showed that 5 core genes (NDUFAB1, NDUFB2, UQCRH, COX7C, NDUFA4) were highly expressed in venous thromboembolism samples, and lowly expression in normal tissue samples, and 2 core genes (NDUFA7, NDUFA6) were lowly expressed in venous thromboembolism samples. CTD analysis showed that 5 genes (NDUFAB1, NDUFB2, UQCRH, COX7C, NDUFA4) were found to be associated with obesity, necrosis, inflammation and hepatomegaly. The result of WB showed that expression level of NDUFB2 and UQCR in venous thromboembolism was higher than that in control group. NDUFB2 and UQCRH are highly expressed in venous thromboembolism with liver cirrhosis, making them potential molecular targets for early diagnosis and precise treatment.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

In Situ Enzymatic Reaction Generates Magnesium-Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration.

Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme-catalyzed reaction is reported to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo-crosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.

Lipidomics of Sannen goat milk subjected to pasteurization and spray drying based on LC-ESI-MS/MS.

The purpose of this study was to evaluate the effects of pasteurization and spray drying on goat milk lipids by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and multiple variable statistics. A total of 1061 lipids assigned to 29 subclasses in raw and thermal-treated groups were identified. One hundred and 85 different lipids (DLs) (VIP ≥ 1 and |Log2FC| ≥ 1.0) were selected from pairwise comparisons of goat milk by different treatments. Glycerophospholipids were the most affected subclasses by thermal processes, especially by spray drying. Five potential lipid markers [(DG (16:1_18:0), TG (18:1_22:1_18:2), Cer (t17:2/31:0), LPC (0:0/20:0), and LPS (20:0/0:0] were used to distinguish different treated goat milk. Moreover, glycerophospholipid metabolism was the primary pathway of DLs. These results would provide more details of lipid profiles in thermally treated (pasteurization and spray drying) goat milk.

Effect of homogenization on lipid profiling in Saanen goat milk based on UHPLC-QTOF-MS lipidomics.

Homogenization might change the lipid composition of goat milk. This study aimed to investigate the lipid profiles, and identify different lipids (DLs) of raw goat milk (RGM) and homogenized goat milk (HGM) using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and multivariate statistics. Fifty-six DLs (VIP ≥ 1 and |Log2FC| ≥ 1.0) were identified from 1057 lipids assigned to 29 subclasses in RGM and HGM. Notably, there were many phosphatidylcholines (PCs) decreased after homogenization, while lysophosphatidylcholines (LPCs) were opposite. Our results provide more details on the impact of homogenization on goat milk lipids.

Denosumab treatment for progressive Enneking stage II cervical giant-cell tumor conservatively.

Cervical giant cell tumor of the bone (GCTB) is a rare, primary benign bone tumor in pediatric patients. Surgery remains the primary choice for treating resectable cervical GCTB. Additional adjuvant therapeutic options are available for patients with unresectable cervical GCTB, including the anti-RANKL monoclonal antibody, denosumab. We represented a case incidentally found in a 7-year-old female, who complained severe craniocervical pain, grade 2-3 dysphagia, dysphonia, hypesthesia, and extremity weakness. The patient showed an impressive clinical response to denosumab, both clinically and radiologically, without adverse events or recurrence. To date, this is the youngest patient ever reported to have a progressive Enneking stage II C3 GCTB treated with denosumab alone. Denosumab can be administered as a single and conservative therapy for pediatric patients with unresectable upper cervical GCTB, avoiding the risks and morbidity of surgical and radiative treatment.

Resection of cervical hemivertebra with occipitocervical - fusion: report on two torticollis cases and literature review.

The objective of this study is to present the two cases of cervical hemivertebra and torticollis, and To describe technique and result of cervical hemivertebra resection and torticollis correction via a anterior-posterior surgical approach and occipitocervical fusion. Cervical hemivertebra, accompanied by abipartite atlas, agenesis of odontoid and C2 segmental type of vertebral artery (VA), is a rare, but complex congenital anomalies, associated with cervical scoliosis and occipitocervical instability. To the best of our knowledge, this is the first report on such congenital anomaly and deformity correction via anterior-posterior hemivertebra resection with occipitocervical fusion. Two patients were presented with torticollis due to congenital cervical hemivertebra accompanied by abipartite atlas, agenesis of odontoid and C2 segmental type of VA. Deformity correction was executed by an anterior-posterior hemivertebra resection and occipitocervical fusion with segment instrumentation. The treatment course was uneventful and clinical outcomes was favorable. The radiographs showed a satisfactory deformity correction with a well-balanced coronal and sagittal alignment. Hemivertebra resection with occipitocervical fusion could correct torticollis with satisfactory clinical and radiographical outcome.

The relationship between adjuvant radiotherapy and survival of osteosarcoma: a case-control study.

To investigate whether adjuvant radiotherapy (RT) is associated with survival rate of osteosarcoma patients. A total of 3938 osteosarcoma patients between 1975 and 2016 from Surveillance, Epidemiology, and End Results (SEER) database were enrolled in this study. Survival rate was obtained by Kaplan-Meier method, with log-rank test identifying the difference. Multivariate Cox regression analysis was used to explore independent prognostic factors. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates in surgery plus adjuvant RT group and surgery alone group were 38.2%, 66.3% (OS), and 41.6%, 68% (CSS), respectively. Multivariate analysis showed that adjuvant RT served as the independent unfavorable prognostic factor for OS and CSS. Based on the propensity score matching (PSM) method, the patients who received adjuvant RT had a poorer prognosis. Adjuvant RT showed an association with survival of osteosarcoma. Patients who received adjuvant RT had poorer survival. In the clinical use of adjuvant RT for osteosarcoma, the potential for reduced survival should be considered.

Surgical strategy and outcomes for thoracolumbar disc herniation with Autologous Bone-Fusion or Cage-Fusion surgery: case series and literature review.

To analyze the clinical characteristics and surgical outcomes of TLDH with Autologous Bone-Fusion for T10-L1 TLDH or Cage-Fusion for T12-L3 TLDH. This is a retrospective multi-center clinical study, involving a total of 43 patients with TLDH who underwent surgery in our institutions from December 2013 to January 2021. In all, 15 of 43 patients (34.9%) with T10-11(2)/T11-12(5)/T12-L1 (8) TLDH underwent Autologous Bone-Fusion surgery and 28 of 43 patients (65.1%) with T12-L1(3)/L1-L2(12)/L2-L3(13) TLDH underwent Cage-Fusion surgery. Demographic data, clinical characteristics and perioperative outcomes were recorded. During the follow-up, pre- to post-operative ODI, VAS back and leg pain scores significantly decreased (P1.2 = 0.001) and the score changes had no significant difference between two groups (P3 = 0.81, 0.59, 0.68). The intraoperative blood loss and operation time showed no significant difference between two groups (P = 0.056, 0.072). The patients showed prominent improvement of hypokinesia and satisfactory rate in two groups (5/7, 71.4% VS 9/12, 75.0%, P = 0.633; 11, 73.3% VS 25, 89.3%, P = 0.281). Notably, no recurrence and severe complications were reported. The choice of surgery approach should be individualized by clinical characteristics and radiology. Selectively Autologous Bone-Fusion for T10-L1 TLDH or Cage-Fusion for T12-L3 TLDH provided adequate nerve decompression and immediate stability. The overall fusion surgical outcomes were satisfactory without major complications during follow-up.

Statistical inference using GLEaM model with spatial heterogeneity and correlation between regions.

A better understanding of various patterns in the coronavirus disease 2019 (COVID-19) spread in different parts of the world is crucial to its prevention and control. Motivated by the previously developed Global Epidemic and Mobility (GLEaM) model, this paper proposes a new stochastic dynamic model to depict the evolution of COVID-19. The model allows spatial and temporal heterogeneity of transmission parameters and involves transportation between regions. Based on the proposed model, this paper also designs a two-step procedure for parameter inference, which utilizes the correlation between regions through a prior distribution that imposes graph Laplacian regularization on transmission parameters. Experiments on simulated data and real-world data in China and Europe indicate that the proposed model achieves higher accuracy in predicting the newly confirmed cases than baseline models.

Facile construction of fluorescent C70-COOH nanoparticles with advanced antibacterial and anti-biofilm photodynamic activity.

Photodynamic antibacterial therapy has been considered as one of the most promising treatments to alleviate the spread of multidrug resistant bacterial pathogens. Given the hypoxic environment of infectious tissues, photosensitizers with reduced oxygen-demand could exhibit superiority upon irradiation. Herein reported is a novel C70-based photosensitizers synthesized by the facile one-step thiol-ene reaction. Various characterization techniques were employed to confirm the structural, photoluminescent properties, photostability and biocompatibility of the as-synthesized C70-COOH nanoparticles. Furthermore, they were capable of efficiently producing reactive oxygen species following both the type I and II mechanistic pathways, thus still generating adequate free radicals under hypoxic condition. Therefore, they could approach and destroy the bacterial cell membrane in the presence of visible light, thereby causing cytoplasmic leakage and eventually achieving broad-spectrum inactivation of four representative bacterial strains. Especially, methicillin-resistant Staphylococcus aureus (MRSA) were completely eliminated after merely 10 minutes irradiation, and the formation of its corresponding biofilm were also greatly inhibited by C70-COOH nanoparticles. These results provide new insights and opportunities for the development of hypoxia-tolerant fullerene-based photosensitizers to combat multidrug resistant bacterial and related infections.

Large Lumbar Lordosis and Coronal Deformity Angular Ratio Are Risk Factors for Adolescent Idiopathic Scoliosis in Patients With Lumbar Spondylolysis.

BACKGROUND: The features of lumbar curves in patients with lumbar spondylolisthesis (LS) are unclear. The aim of this retrospective study was to present the clinical and radiologic characteristics of scoliosis due to LS and LS concurrent with main thoracolumbar/lumbar adolescent idiopathic scoliosis (AIS). METHODS: This study was conducted as a single-center retrospective comparative study on 56 pediatric spondylolisthesis patients with main thoracolumbar/lumbar curves. Cases were divided into 2 groups according to the course of scoliosis after spinal surgery of LS. Sagittal spinopelvic parameters and scoliotic characteristics were compared between the 2 groups. RESULTS: The prevalence of scoliosis was 15.3% in pediatric LS patients in our study population. Lumbar lordosis (LL), Cobb angle, apical rotation, and coronal deformity angular ratio (C-DAR) were higher in the LS concurrent with AIS group than in the LS with functional scoliosis group (P < 0.05), while curve span, apical vertebral translation, and central sacral vertical line to C7 plumb line were lower (P < 0.05). Logistic regression analyses and receiver operating characteristic curves showed that LL and C-DAR were significant risk factors of unresolved lumbar curves after spinal surgery for LS, with a cutoff value of 51.5°and 3.5, respectively. CONCLUSIONS: Lumbar scoliosis may develop due to LS, or a concurrent condition to LS. LL and C-DAR are the features that differentiate AIS from functional scoliosis in patients with LS.

Multilevel unilateral versus bilateral pedicular percutaneous vertebroplasty for osteoporotic vertebral compression fractures.

Study design: Retrospective study. Objective: Controversy exists over the need for unilateral vs. bilateral pedicular percutaneous vertebroplasty (PVP) for patients with osteoporotic vertebral compression fractures (OVCFs). Clinical research is scarce comparing two approaches for multi-level PVP. This study aimed at evaluating the clinical and radiographic outcomes of multi-level PVP using two approaches for OVCFs. Methods: Seventy-eight patients with OVCFs undergoing multi-level PVP were enrolled including 36 patients undergoing unilateral PVP and 42 undergoing bilateral PVP. The clinical and radiological assessments including the Visual Analogue Scale (VAS), sagittal and coronal segmental Cobb, vertebral compression ratio (VCR), and vertebral sides ratio (VSR) were evaluated preoperatively and postoperatively. Results: All patients achieved a minimum 2-year follow-up. A total of 164 fractured vertebrae were enrolled. Regarding clinical efficacy, the VAS score improved in both groups after surgery, but the two groups did not differ significantly. The changes tendency in Sagittal Segmental Cobb, VSR, and VCR were similar postoperatively, and no statistically significant difference between groups. As for the Coronal Segmental Cobb angle, patients in unilateral and bilateral groups were shown to have 5.0° ± 4.0° and 2.6° ± 2.2° degrees loss of correction at a minimum 2-years follow-up duration, respectively. The loss of correction in the Coronal Segmental Cobb of unilateral group was significantly greater than that of bilateral group. Conclusion: Both multi-level unilateral and bilateral pedicular PVP achieved significant pain reduction and vertebral height restoration. Moreover, the bilateral PVP has shown advantages in stabilizing Coronal Cobb angle in patients with OVCFs.

Treatment of thoracolumbar fractures by temporary posterior instrumentation with selective fusion schemes.

OBJECTIVE: This retrospective study investigated the clinical and radiographic outcomes following temporary transpedicular posterior instrumentation between two cohorts of patients with thoracolumbar fractures (TLF) who underwent selective or bi-segments intervertebral articular process fusion. METHODS: Patients with TLF who underwent the temporary posterior fixation with selective fusion (Group SF), or bi-segments fusion (Group BF) were studied. Superior intervertebral articular process and interlaminar fusion were performed in Group SF, whereas in Group BF, the patients underwent bi-segments fusion in both superior and inferior articular processes, as well as interlaminar fusion. We measured the distal and proximal intervertebral mobility, regional kyphotic angle, and vertebral height before and after surgery in both groups. Greenough Low-Back Outcome Score was used to assess the clinical outcomes. RESULTS: Sixty-five patients with TLF from T12 to L2 fractures were enrolled in the study period: 33 patients in the Group SF and 32 patients in the Group BF. All the patients experienced fracture healing (mean follow-up time: 19.7 months). The mean postoperative functional outcomes were 65.0 ± 2.0 points for the Low-Back Outcome Score in the Group SF and 65.2 ± 1.8 for the Group BF. A progressive regional kyphotic angle was observed with time regardless of fusion but was not significantly different between the two groups. There was a statistical difference between unfused inferior proximal adjacent and inferior distal adjacent segment regardless of fracture segments. CONCLUSIONS: The strategy of selective fusion is reported to be useful for the treatment of patients with TLF. The motion in the un-fused and adjacent segment could be better regained after instrumentation removal in the selective fusion group. LEVEL OF EVIDENCE: Level 3.

Design and synthesis of highly fluorescent and stable fullerene nanoparticles as probes for folic acid detection and targeted cancer cell imaging.

Rational design and construction of fullerene derivatives play significant roles in the development of applications for sensing, marking and imaging in biomedical fields. In the present work, a novel type of C60 fluorescent nanoparticle (C60 FNP) was synthesized by a combination of thiol-ene chemistry and modification with folic acid (FA). The as-prepared C60 FNPs exhibited intense blue luminescence with a relatively high quantum yield of 26%, which is higher than that of any other reported fluorescent fullerene-based nanomaterial. Moreover, they revealed superior photobleaching resistance under constant UV lamp illumination for 5 h and excellent photostablity after 9 months of storage in water. Due to the mutual hydrogen bond interaction, the obtained C60 FNPs were capable of acting as a sensitive and specific probe for FA detection and quantification, with a liner range of 0 to 80 µM and a detection limit of 0.24 µM. Satisfactory recoveries (95.4%-105.2%) were obtained from a series of actual samples, further confirming the feasibility of this nanoprobe. Additionally, taking advantage of the FA moiety, the C60 FNPs had easy access to penetrate into cancer cells with higher expression levels of folate receptors, thereby achieving the function of targeted cellular imaging.