Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.

Identification and bioinformatics analysis of lncRNAs in serum of patients with ankylosing spondylitis.

OBJECTIVES: The aim of this study was to explore the long non-coding RNA (lncRNA) expression profiles in serum of patients with ankylosing spondylitis (AS). The role of these lncRNAs in this complex autoimmune situation needs to be evaluated. METHODS: We used high-throughput whole-transcriptome sequencing to generate sequencing data from three patients with AS and three normal controls (NC). Then, we performed bioinformatics analyses to identify the functional and biological processes associated with differentially expressed lncRNAs (DElncRNAs). We confirmed the validity of our RNA-seq data by assessing the expression of eight lncRNAs via quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 AS and 20 NC samples. We measured the correlation between the expression levels of lncRNAs and patient clinical index values using the Spearman correlation test. RESULTS: We identified 72 significantly upregulated and 73 significantly downregulated lncRNAs in AS patients compared to NC. qRT-PCR was performed to validate the expression of selected DElncRNAs; the results demonstrated that the expression levels of MALAT1:24, NBR2:9, lnc-DLK1-35:13, lnc-LARP1-1:1, lnc-AIPL1-1:7, and lnc-SLC12A7-1:16 were consistent with the sequencing analysis results. Enrichment analysis showed that DElncRNAs mainly participated in the immune and inflammatory responses pathways, such as regulation of protein ubiquitination, major histocompatibility complex class I-mediated antigen processing and presentation, MAPkinase activation, and interleukin-17 signaling pathways. In addition, a competing endogenous RNA network was constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs (MALAT1:24 and NBR2:9). We further found the expression of MALAT1:24 and NBR2:9 to be positively correlated with disease severity. CONCLUSION: Taken together, our study presents a comprehensive overview of lncRNAs in the serum of AS patients, thereby contributing novel perspectives on the underlying pathogenic mechanisms of this condition. In addition, our study predicted MALAT1 has the potential to be deeply involved in the pathogenesis of AS.

Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient.

BACKGROUND: Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome. CASE PRESENTATION: A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions. CONCLUSIONS: This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.

High precision dual-modulation differential terahertz ATR sensor for liquid measurements.

We describe a highly sensitive and stable quantum-cascade-laser-based attenuated total reflection (ATR) terahertz sensor for the detection of very low concentration solutions, using a dual-modulation differential approach and ATR geometry. This sensor offers a very high dynamic range and a long-term stability of 40 dB, which extends the potential of terahertz radiation for the analysis of liquid and biological samples. The performance is illustrated by measurements on standard solutions of ions, sugars, and proteins, for concentrations down to 1 µM.

Relativistic DFT Probe for Reaction Energies and Electronic/Bonding Properties of Polypyrrolic Hetero-Bimetallic Actinide Complexes: Effects of Uranyl endo-Oxo Functionalization.

A series of hetero-bimetallic actinide complexes of the Schiff-base polypyrrolic macrocycle (L), featuring cation-cation interactions (CCIs), were systematically investigated using relativistic density functional theory (DFT). The tetrahydrofuran (THF) solvated complex [(THF)(OUVIOUIV)(THF)(L)]2+ has high reaction free energy (ΔrG), and its replacement with electron-donating iodine promotes the reaction thermodynamics to obtain uranyl iodide [(I)(OUVIOUIV)(I)(L)]2+ (UVI-UIV). Retaining this coordination geometry, calculations have been extended to other An(IV) (An = Th, Pa, Np, Pu), i.e., for the substitution of U(IV) to obtain UVI-AnIV. As a consequence, the reaction free energy is appreciably lowered, suggesting the thermodynamic feasibility for the experimental synthesis of these bimetallic complexes. Among all UVI-AnIV, the electron-spin density and high-lying occupied orbitals of UVI-PaIV show a large extent of electron transfer from electron-rich Pa(IV) to electron-deficient U(VI), leading to a more stable UV-PaV oxidation state. Additionally, the shortest bond distance and the comparatively negative Eint of the Pa-Oendo bond suggest more positive and negative charges (Q) of Pa and endo-oxo atoms, respectively. As a result of the enhanced Pa-Oendo bond and strong CCI in UVI-PaIV along with the corresponding lowest reaction free energy among all of the optimized complexes, uranyl species is a better candidate for the experimental synthesis in the ultimate context of environmental remediation.

Dynamics of Cell Membrane Permeabilization by Saponins Using Terahertz Attenuated Total Reflection.

Understanding the relevant parameters of the formation of pores during permeabilization is very challenging for medical applications. Several components are involved: the arrival of the permeabilizing molecules to the membrane, the efficiency of formation of the pores and their specific dynamics, and the flux of molecules through the plasma membrane. Using attenuated total reflection in the terahertz domain, we studied the dynamics of Madine-Darby canine kidney cells after permeabilization by saponin molecules. We developed an analytical model taking into account saponin molecule diffusion, cell geometry, cytosol molecule diffusion, and pore dynamics. We also studied the effect of possible pore overlapping on the cell membrane, introducing a dimensionless quantity that is the ratio between overlapping and diffusive effects. Pores are found to be static within 1 h after their creation, hinting that the diffusion of the saponin molecules to the membrane is the limiting factor in our experiments.

MicroRNA-218-5p relieves postmenopausal osteoporosis through promoting the osteoblast differentiation of bone marrow mesenchymal stem cells.

MicroRNAs (miRs) are short noncoding RNAs that play key regulatory roles in osteoblast differentiation. In this study, the specific regulatory roles of miR-218-5p on postmenopausal osteoporosis (PMOP) were investigated. The mouse model of PMOP was established by bilateral ovariectomy, and the injection of miR-218-5p mimics significantly relieved PMOP degree. Then, bone marrow mesenchymal stem cells (BMMSCs) isolated from PMOP mice were induced into osteoblasts. When compared with normal BMMSCs, PMOP BMMSCs exhibited significantly lower alkaline phosphatase (ALP) activity and less mineralized nodules, as well as downregulated miR-218-5p, Runx2, Osterix, COL1A1, and OCN after induction (P < .05). The transfection of miR-218-5p mimics, and inhibitor significantly promoted, inhibited the osteoblast differentiation of PMOP BMMSCs, respectively. In addition, COL1A1 was a target of miR-218-5p. The transfection of miR-218-5p mimics into PMOP BMMSCs significantly upregulated COL1A1 at 14th and 21st day post-induction, but not at 7th day. Our findings suggest miR-218-5p may relieve PMOP through promoting the osteoblast differentiation of BMMSCs.

Main-Group Metals Stabilized Polypyrrolic Uranyl(V) Complexes via Cation-Cation Interaction with the Uranyl exo-Oxo Atom: A Relativistic Density Functional Theory Study.

To explore the innovative uranyl(V) complexes by deeply understanding their coordination stability, relativistic density functional theory calculations have been performed to investigate the experimentally reported [(py)(R2AlOUVO)(py)(H2L)] [R = Me (1), iBu (2)] and [{(py)3MOUVO}(py)(H2L)] [M = Li (3), Na (4), K (5)] and their uranyl(VI) counterparts. Structural and topological analyses along with transformation-reaction energies and redox potentials were systematically studied. Geometrical and quantum theory of atoms in molecules analyses implied a linear U-Oexo-M feature in 1-3 and a bent one in 4 and 5. The calculated free energies (ΔrG) of reactions transforming 1/2 into 3/4/5 confirmed a higher stability of the latter ones, which were further corroborated by their reduction potentials (E0). The E0 value of 5 versus uranyl(VI) is close to its experimental value, particularly in solvation with spin-orbit coupling. The highest occupied and lowest unoccupied molecular orbitals of uranyl(V) and uranyl(VI) have predominant U(5fδ) character. Compared to mononuclear uranyl(VI), the coordination of aluminum and alkali metals to uranyl exo-oxo significantly contributes to the stabilization of uranyl(V) by altering the E0 value from -1.59 to -0.85, -0.91, -1.33, -1.50, and -1.46 V, respectively. The calculation results show a more positive E0 than that of the precursor 6VI/6 without exo-oxo coordination. The calculated E0 values of 3-5 are certainly more negative than those of 1 and 2. The alkali metals were found to activate U═O bonds more easily/readily than aluminum by coordination to the exo-oxo atom. In brief, the uranyl exo-oxo cation-cation-interaction enhanced the reduction ability from its uranyl(VI) analogue and raised the stability of the UV center.

A posterior-only approach for ankylosing spondylitis (AS) with thoracolumbar pseudoarthrosis: a clinical retrospective study.

BACKGROUND: Surgical treatment has been recommended by most surgeons to treat pseudarthrosis in ankylosing spondylitis (AS). However, there is still some debate on the necessity of anterior fusion. There is very limited literature on the treatment and surgical outcomes of thoracolumbar pseudarthrosis in AS patients treated through a posterior-only approach. METHODS: From January 1, 2012 to December 31, 2017, a total of 42 cases diagnosed with thoracolumbar pseudarthrosis in AS patients with moderate kyphosis were included in this study. All of the patients received posterior-only kyphosis correction, internal fixation and fusion without anterior fusion, and underwent at least 2 years of follow-up. Clinical and radiographic results and complications were assessed. RESULTS: All of the patients were followed up for an average of 35.3 months (range, 24-48 months), and they achieved successful bone graft fusion at the pseudarthrosis sites. Satisfactory radiographic changes were achieved in these patients. The Cobb angles of global kyphosis (GK) were corrected from 53.2 ± 5.4 degrees preoperatively to 33.2 ± 4.3 degrees postoperatively, and to 36.1 ± 5.3 degrees at the latest follow-up. The Cobb angles of local kyphosis (LK) were corrected from 43.3 ± 4.6 degrees preoperatively to 26.8 ± 3.3 degrees postoperatively, and to 28.2 ± 3.6 degrees at the latest follow-up. The mean sagittal vertical axis (SVA) were corrected from 7.6 ± 4.2 cm preoperatively to 4.3 ± 2.1 cm postoperatively, and to 4.8 ± 2.3 cm at the latest follow-up. No serious neurological complication or deep wound infection was found in these 42 patients. CONCLUSION: Posterior-only kyphosis correction and fixation without anterior fusion can achieve excellent bone fusion and satisfactory improvement in AS patients with thoracolumbar pseudarthrosis. This method may be a good choice for treating thoracolumbar pseudarthrosis in AS patients with moderate kyphosis.

A novel 96.5Sn3Cu0.5Mn nanosolder with enhanced wettability applied to nanosoldering of WO3 nanomaterial.

Nano-soldering relying on a sacrificial nanosolder, is a flexible interconnection technique, having promising applications in joining nanosized functional materials; that is an essential step in the assembly of nano-devices. In a soldering, the wettability is important in the bonding of two nanomaterial, which determines the quality of the junction. Tungsten trioxide nanomaterial has unique characteristics such as electro-, opto-, gaso-chromic. To assemble this nanomaterial into functional nano-devices, a superior nanosolder is necessary. The conventional SnCu nanosolder has been chosen, but its wetting on WO3 is unsatisfactory. Here, our study indicates that the SnCu wettability on WO3 material has been improved greatly by adding minor manganese, in which the contact angle has a significant change from 73.2° to 41.7°. Then the wetting mechanism is investigated by observing the soldering interface. Lastly, a more robust and higher-reliable junction has been obtained by thermal soldering two individual WO3 nano-objects into a cross-shaped pattern.

MiR-9 promotes osteoblast differentiation of mesenchymal stem cells by inhibiting DKK1 gene expression.

The aim of this study is to investigate the role of miR-9 and its mechanism on the osteoblast differentiation of mesenchymal stem cells. Real-time PCR and western blotting were used to study gene expression. Assay of Alkaline phosphatase activity and alizarin red staining were used to examine osteoblast differentiation. Transfection of miR-9 mimics or lent-shmiR-9 was used to modulate the level of miR-9 in C2C12. Overexpression of miR-9 in C2C12 cells stimulated alkaline phosphatase activity and osteoblast mineralization, as well as the expression of osteoblast marker genes Col I, Ocn and Bsp. Gene silencing of miR-9 in C2C12 resulted in the suppression of alkaline phosphatase activity and osteoblast mineralization, as well as the expression of Col I, Ocn and Bsp. DKK1 mRNA was not affected by miR-9 overexpression, however, DKK1 protein was significantly decreased. Moreover, DKK1 3'-UTR mediated transcriptional luciferase activity was also significantly suppressed by miR-9 overexpression. DKK1 mRNA was not affected by miR-9 gene silencing, however, DKK1 protein was significantly stimulated. Moreover, DKK1 3'-UTR mediated transcriptional luciferase activity was significantly stimulated by miR-9 gene silencing, and suppressed by miR-9 overexpression, however, DKK1 3'-UTR mutant mediated luciferase activity was unaffected. The siRNA derived gene silencing of DKK1 blocked the inhibiting effect of shmiR-9 on the expression of alkaline phosphatase; and blocked the inhibiting effect of shmiR-9 on the expression of ColI, Ocn and Bsp. MiR-9 promotes osteoblast differentiation of mesenchymal cell C2C12 by suppressing the gene expression of DKK1.

Highly valence-diversified binuclear uranium complexes of a schiff-base polypyrrolic macrocycle: prediction of unusual structures, electronic properties, and formation reactions.

On the basis of relativistic density functional theory calculations, homo- and heterovalent binuclear uranium complexes of a polypyrrolic macrocycle in a U-O-U bridging fashion have been investigated. These complexes show a variety of oxidation states for uranium ranging from III to VI, which have been confirmed by the calculated electron-spin density on each metal center. An equatorially 5-fold uranyl coordination mode is suitable for hexavalent uranium complexes, while silylation of the uranyl oxo is favored by pentavalent uranium. Uranyl oxo ligands are not required anymore for the coordination environment of tetra- and trivalent uranium because of their replacement by strong donors such as tetrahydrofuran and iodine. Optimization of binuclear U(VI)-U(III) complexes with various coordinating modes of U(III), donor numbers, and donor types reveals that 0.5-1.0 electron has been transferred from U(III) to U(VI). Consequently, U(V)-U(IV) complexes are more favorable. Electronic structures and formation reactions of several representative uranium complexes were calculated. For example, a 5f-based σ(U-U) bonding orbital is found in the diuranium(IV) complex, rationalizing the fact that it shows the shortest U-U distance (3.82 Å) among the studied binuclear complexes.

[Comparison of clinical efficacies of single segment transforaminal lumbar interbody fusion with cage versus autogenous morselized bone for degenerative lumbar spinal stenosis: a prospective randomized controlled study].

OBJECTIVE: To compare the clinical efficacies of single segment transforaminal lumbar interbody fusion (TLIF) with cage versus autogenous morselized bone for degenerative lumbar spinal stenosis. METHODS: A total of 87 patients undergoing single segment TLIF were randomly divided into 2 groups. A cage was implanted into intervertebral space in group A patients while autogenous morselized bone in group B patients. Operative duration, blood loss, length of stay and cost of hospitalization of two groups were recorded. They were followed up at 1 week, 12, 24 months post-operation. Oswestry disability index (ODI), visual analogue scale (VAS) fusion rates, intervertebral space and foramen height restoration, lumbar lordosis and postoperative complications were compared between two groups. RESULTS: No significant inter-group difference existed in operative duration, blood loss or length of stay. However, the average hospitalization cost in group A were 18% higher than that of group B (P < 0.05). Both groups achieved excellent clinical outcomes within 2 years. ODI, VAS score improvement rates and postoperative complication rates were not statistically different. Lumbar fusion rate was 86.7% in group A versus 85.7% in group B after 2 years. And there was no significant difference (P > 0.05). The heights of intervertebral space and foramen in group A achieved a better recovery than those of group B. Both groups had similar improvements of lumbar lordosis. CONCLUSION: For degenerative lumbar spinal stenosis, usage of interbody cage is more effective in terms of recovery of intervertebral space and foraminal height compared with usage of bone graft. However it brings no better clinical efficacy while the usage of autogenous morselized bone is more cost-effective. Two grafting methods yield similar overall clinical outcomes.

RNA sequencing and bioinformatics analysis of differentially expressed genes in the peripheral serum of ankylosing spondylitis patients.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease characterized by spinal and sacroiliac arthritis, but its pathogenesis and genetic basis are largely unclear. METHODS: We randomly selected three serum samples each from an AS and a normal control (NC) group for high-throughput sequencing followed by using edgeR to find differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, Reactome pathway analyses, and Gene Set Enrichment Analysis were used to comprehensively analyze the possible functions and pathways involved with these DEGs. Protein-protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of these DEGs were identified using MCODE and CytoHubba plugins. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression levels of candidate genes in serum samples from AS patients and healthy controls. RESULTS: We successfully identified 100 significant DEGs in serum. When we compared them with the NC group, 49 of these genes were upregulated in AS patients and 51 were downregulated. GO function and pathway enrichment analysis indicated that these DEGs were mainly enriched in several signaling pathways associated with endoplasmic reticulum stress, including protein processing in the endoplasmic reticulum, unfolded protein response, and ubiquitin-mediated proteolysis. We also constructed a PPI network and identified the highly connected top 10 hub genes. The expression levels of the candidate hub genes PPARG, MDM2, DNA2, STUB1, UBTF, and SLC25A37 were then validated by RT-qPCR analysis. Finally, receiver operating characteristic curve analysis suggested that PPARG and MDM2 may be the potential biomarkers of AS. CONCLUSIONS: These findings may help to further elucidate the pathogenesis of AS and provide valuable potential gene biomarkers or targets for the diagnosis and treatment of AS.

Terahertz Spectroscopy Sheds Light on Real-Time Exchange Kinetics Occurring through Plasma Membrane during Photodynamic Therapy Treatment.

Methods to follow in real time complex processes occurring along living cell membranes such as cell permeabilization are rare. Here, the terahertz spectroscopy reveals early events in plasma membrane alteration generated during photodynamic therapy (PDT) protocol, events which are not observable in any other conventional biological techniques performed in parallel as comparison. Photodynamic process is examined in Madin-Darby canine kidney cells using Pheophorbide (Pheo) photosensitizer alone or alternatively encapsulated in poly(ethylene oxide)-block-poly(ε-caprolactone) micelles for drug delivery purpose. Terahertz spectroscopy (THz) reveals that plasma membrane permeabilization starts simultaneously with illumination and is stronger when photosensitizer is encapsulated. In parallel, the exchange of biological species is assessed. Over several hours, this conventional approach demonstrates significant differences between free and encapsulated Pheo, the latter leading to high penetration of propidium iodide, Na+ and Ca2+ ions, and a high level of leakage of K+ , ATP, and lactate dehydrogenase. THz spectroscopy provides, in a single measurement, the relative number of defects per membrane surface created after PDT, which is not achieved by any other method, providing early, sensitive real-time information. THz spectroscopy is therefore a promising technique and can be applied to any biological topic requiring the examination of short-term plasma membrane permeabilization.

Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study.

Chimeric antigen receptor (CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts. Allogeneic CAR-T cells, generated from healthy donor T cells, can provide ready-to-use, blast-free therapeutic products, but their application could be complicated by graft-versus-host disease (GvHD) and host rejection. Here we developed healthy donor-derived, CD7-targeting CAR-T cells (RD13-01) with genetic modifications to resist fratricide, GvHD and allogeneic rejection, as well as to potentiate antitumor function. A phase I clinical trial (NCT04538599) was conducted with twelve patients recruited (eleven with T cell leukemia/lymphoma, and one with CD7-expressing acute myeloid leukemia). All patients achieved pre-set end points and eleven proceeded to efficacy evaluation. No dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade ≥ 3) were observed. 28 days post infusion, 81.8% of patients (9/11) showed objective responses and the complete response rate was 63.6% (7/11, including the patient with AML). 3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation. With a median follow-up of 10.5 months, 4 patients remained in complete remission. Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) reactivation was observed in several patients, and one died from EBV-associated diffuse large B-cell lymphoma (DLBCL). Expansion of CD7-negative normal T cells was detected post infusion. In summary, we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7+ hematological malignancies. Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7+ tumors.

Is it safe to back out pedicle screws after augmentation with polymethyl methacrylate or calcium phosphate cement? A biomechanical study.

STUDY DESIGN: Biomechanical cadaveric study. OBJECTIVE: To determine the torque required to remove pedicle screws augmented with polymethyl methacrylate (PMMA) or calcium phosphate cement (CPC); thus, proving the safety of back out of augmented screws in the osteopotoric model, which would be a more dangerous setting than the nonosteoporotic model. SUMMARY OF BACKGROUND DATA: To our knowledge, no earlier study has characterized the safety of backing out pedicle screw augmented with PMMA or CPC. METHODS: Pedicle screws were inserted in 24 osteoporotic vertebrae (48 pedicles). The maximal insertion torque and pullout strength of each screw were recorded. After pullout of the pedicle screws, the vertebrae were then randomized into 2 groups of 12 (24 pedicles) each. PMMA was injected into the pedicles in the first group and CPC was injected into the second group after which the pedicle screws were inserted. The pedicle screws were inserted into the pedicle holes augmented with PMMA or CPC, respectively. Finally, all augmented screws were backed out and the maximal removal torque was recorded using a digital torque wrench. RESULTS: Throughout the study, no incidence of pedicle or lamina fractures was observed. The average insertion torque was 0.5±0.27 and 0.45±0.29 N·m for groups 1 and 2, respectively (P=0.724). The average pullout strength was 723.1±391.7 and 671.2±383.0 N (P=0.950). After cement augmentation, the average removal torque was 0.77±0.31 and 0.81±0.26 N·m for PMMA and CPC, respectively (P=0.494). CONCLUSIONS: The results of this study showed that pedicle screws can be easily and safely backed out after augmentation with PMMA or CPC. The result of CPC, however, may only be valid before any bony ingrowth.

Poly[[aqua-(µ(5)-1H-benzimidazole-5,6-dicarboxyl-ato)(µ(4)-1H-benzimidazole-5,6-dicarboxyl-ato)dibarium] 4.5-hydrate].

The polymeric title compound, {[Ba(2)(C(9)H(4)N(2)O(4))(2)(H(2)O)]·4.5H(2)O}(n), adopts a layer structure parallel to (001) in which adjacent Ba(II) atoms are connected by two benzimidazole-5,6-dicarboxyl-ate dianions, one functioning in a µ(4)-bridging mode and the other in a µ(5)-bridging mode. The Ba atom having water in its coordination environment as well as the Ba atom without water exist in a nine-coordinate polyhedron of O atoms; the geometry is difficult to derive. Lattice water mol-ecules occupy the space between layers and inter-act with the layers through O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds. ne of the five lattice water molecules is equally disordered around an inversion centre and shows half-occupancy.

Subaxial cervical pedicle screw insertion with newly defined entry point and trajectory: accuracy evaluation in cadavers.

Successful placement of cervical pedicle screws requires accurate identification of both entry point and trajectory. However, literature has not provided consistent recommendations regarding the direction of pedicle screw insertion and entry point location. The objective of this study was to define a guideline regarding the optimal entry point and trajectory in placing subaxial cervical pedicle screws and to evaluate the screw accuracy in cadaver cervical spines. The guideline for entry point and trajectory for each vertebra was established based on the recently published morphometric data. Six fresh frozen cervical spines (C3-C7) were used. There were two men and four women. After posterior exposure, the entry point was determined and the cortical bone of the entry point was removed using a 2-mm burr. Pilot holes were created with a cervical probe based on the guideline using fluoroscopy. After tapping, 3.5-mm screws with appropriate length were inserted. After screw insertion, every vertebra was dissected and inspected for pedicle breach. The pedicle width, height, pedicle transverse angulation and actual screw insertion angle were measured. A total of 60 pedicle screws were inserted. No statistical difference in pedicle width and height was found between the left and right sides for each level. The overall accuracy of pedicle screws was 83.3%. The remaining 13.3% screws had noncritical breach, and 3.3% had critical breach. The critical breach was not caused by the guideline. There was no statistical difference between the pedicle transverse angulation and the actual screw trajectory created using the guideline. There was statistical difference in pedicle width between the breach and non-breach screws. In conclusion, high success rate of subaxial cervical pedicle screw placement can be achieved using the recently proposed operative guideline and oblique views of fluoroscopy. However, careful preoperative planning and good surgical skills are still required to ensure screw placement accuracy and to reduce the risk of neural and vascular injury.

Repair mechanism of astrocytes and non-astrocytes in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a destructive disease that incurs huge personal and social costs, and there is no effective treatment. Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus, the pathogenesis of SCI is still under investigation. AIM: To determine the key genes based on the modularization of in-depth analysis, in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI. METHODS: Firstly, the differences between injured and non-injured spinal cord of astrocyte (HA), injured and non-injured spinal cord of non-astrocyte (FLOW), injured spinal cord of non-injured astrocyte (HA) and non-injured spinal cord of non-astrocyte (FLOW), and non-injured spinal cord of astrocyte (HA) and non-astrocyte (FLOW) were analyzed. The total number of differentially expressed genes was obtained by merging the four groups of differential results. Secondly, the genes were co-expressed and clustered. Then, the enrichment of GO function and KEGG pathway of module genes was analyzed. Finally, non-coding RNA, transcription factors and drugs that regulate module genes were predicted using hypergeometric tests. RESULTS: In summary, we obtained 19 expression modules involving 5216 differentially expressed genes. Among them, miR-494, XIST and other genes were differentially expressed in SCI patients, and played an active regulatory role in dysfunction module, and these genes were recognized as the driving genes of SCI. Enrichment results showed that module genes were significantly involved in the biological processes of inflammation, oxidation and apoptosis. Signal pathways such as NF-kappa B/A20, AMPK and MAPK were significantly regulated. In addition, non-coding RNA pivot (including miR-136-5p and let-7d-5p, etc.) and transcription factor pivot (including NFKB1, MYC, etc.) were identified as significant regulatory dysfunction modules. CONCLUSION: Overall, this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI. These findings helped to reveal the core dysfunction modules, potential regulatory factors and driving genes of the disease, and to improve our understanding of its pathogenesis.