Micro-computed tomography analysis and histological observation of the screw-bone interface of novel porous scaffold core pedicle screws and hollow lateral hole pedicle screws: a comparative study in Bama pigs.

OBJECTIVE: Screw loosening is a common complication of pedicle screw internal fixation surgery. This study aimed to investigate whether the application of a porous scaffold structure can increase the contact area between screws and bone tissue by comparing the bone ingrowth and screw-bone interface of porous scaffold core pedicle screws (PSCPSs) and hollow lateral hole pedicle screws (HLHPSs) in the lumbar spine of Bama pigs. METHODS: Sixteen pedicle screws of both types were implanted into the bilateral pedicles of the L1-4 vertebrae of two Bama pigs. All Bama pigs were sacrificed and the lumbar spine was freed into individual vertebrae at 16 weeks postoperatively. After the vertebrae were made into screw-centered specimens, micro-computed tomography (micro-CT) analysis and histological observation were performed to assess the screw-bone interface and bone growth around and within the screws. RESULTS: We found that the bone condition around PSCPSs and HLHPSs did not show significant differences on micro-CT three-dimensional reconstruction images. CT transverse views showed different bone growth inside the two screws. In PSCPSs, bone tissue was seen to fill the internal pores and was evenly distributed around each strut. Inside HLHPSs, bone growth was confined to one side of the screw and did not fill the entire cavity. Osteometric analysis showed that bone volume fraction (BVF) and trabecular number (Tb.N), the parameters representing bone mass, were higher in PSCPSs than in HLHPSs. These differences were not statistically significant (P>0.05). Histological observations visualized that the osseointegration within PSCPSs was superior to that of HLHPSs, and the tight integration of bone tissue with the porous scaffold resulted in a larger screw-bone integration area in PSCPSs than in HLHPSs. CONCLUSIONS: Compared with HLHPSs, PSCPSs possessing a porous scaffold core could promote bone ingrowth and osseointegration, resulting in an effective enhancement of the combined area of the screw-bone interface.

Biomechanical Properties of Novel Porous Scaffold Core and Hollow Lateral Hole Pedicle Screws: A Comparative Study in Bama Pigs.

OBJECTIVE: Screw loosening is a common complication of internal fixation of pedicle screw. Therefore, the development of a pedicle screw with low loosening rate and high biosafety is of great clinical significance. This study aimed to investigate whether the application of a porous scaffold structure can improve the stability of pedicle screws by comparing the biomechanical properties of novel porous scaffold core pedicle screws (PSCPSs) with those of hollow lateral hole pedicle screws (HLHPSs) in a porcine lumbar spine. METHODS: Thirty-two pedicle screws of both types were implanted bilaterally into the L1-4 vertebrae of four Bama pigs, with our newly designed PSCPSs on the right and HLHPSs on the left. All the Bama pigs were sacrificed 16 weeks postoperatively, and the lumbar spine was freed into individual vertebrae. Biomechanical properties of both the pedicle screws were evaluated using pull-out tests, as well as cyclic bending and pull-out tests, while the mechanical properties were assessed using three-point bending tests. The data generated were statistically analyzed using paired-sample t-tests and two independent sample t-tests. RESULTS: We found that the maximal pull-out forces before and after cyclic bending of the PSCPSs (1161.50 ± 337.98 N and 1075.25 ± 223.33 N) were significantly higher than those of the HLHPSs (948.38 ± 194.32 N and 807.13 ± 242.75 N) (p < 0.05, p < 0.05). In 800 cycles of the bending tests, neither PSCPS nor HLHPS showed loosening or visible detachment, but their maximal pull-out forces after cyclic bending tests decreased compared to those in cycles without cyclic bending tests (7.43% and 14.89%, respectively), with no statistical significance (p > 0.05 and p > 0.05, respectively). Additionally, both screws buckled rather than broke in the three-point bending tests, with no statistically significant differences between the maximal bending load and modulus of elasticity of the two screws (p > 0.05 and p > 0.05, respectively). CONCLUSIONS: Compared with the HLHPSs, the PSCPSs have greater pull-out resistance and better fatigue tolerance with appropriate mechanical properties. Therefore, PSCPSs theoretically have significant potential for clinical applications in reducing the incidence of loosening after pedicle screw implantation.

A Novel Method to Improve the Accuracy and Stability of the 3D Guide Template Technique Applied in Upper Cervical Spine Surgery.

AIM: To evaluate the safety and accuracy of C1 and C2 pedicle screw placement using a three-dimensional (3D)-printed double template and compare them with those of the conventional method in a clinical study. MATERIAL AND METHODS: DICOM format data from 60 cases with C1-C2 instability were obtained after computed tomography (CT) was performed. A total of 32 cases underwent surgery via the free-hand technique, whereas 28 cases underwent surgery via a 3D-printed "pointing-drilling" guide template. The ideal trajectory of the C1 and C2 pedicle screws was designed using a baseplate as a separate complementary template for the corresponding posterior C1-C2 anatomical surface, after which the "pointingdrilling" guide template was materialized using a 3D printing machine. The 3D-printed "pointing-drilling" guide template, which was sterilized with low-temperature plasma, was used to locate the starting point and determine the drill trajectory during surgery. The positions of the screws in the axial and sagittal planes of the CT scan were observed and categorized into four grades, after which the operative time, fluoroscopy time, and intraoperative bleeding in the two groups were compared. RESULTS: No significant difference (p > 0.05) in each screw classification grade was observed between the free-hand and "pointingdrilling" template groups; however, a significant difference was observed (p=0.048) between these two groups. A significant difference (p < 0.05) in fluoroscopy times was observed between the free-hand and "pointing-drilling" template groups. Conversely, no significant differences were observed in bleeding (p=0.491) and operative time (p=0.309) between the free-hand and "pointingdrilling" template groups. CONCLUSION: The 3D-printed "pointing-drilling" guide template technique promoted more secure C1 and C2 pedicle screw placement compared with the free-hand technique in clinics.

Enantio- and diastereodivergent synthesis of fused indolizines enabled by synergistic Cu/Ir catalysis.

Highly diastereo-/enantioselective assembly of 2,3-fused indolizine derivatives could be easily available through a cascade allylation/Friedel-Crafts type reaction enabled by a synergistic Cu/Ir catalysis. This designed protocol provides an unprecedented and facile route to enantioenriched indolizines bearing three stereogenic centers in moderate to high yields with excellent stereoselective control, which also featured broad substrate generality. Remarkably, four stereoisomers of the 2,3-fused indolizine products could be efficiently constructed in a predictable manner through the pairwise combination of copper and iridium catalysts. The synthetic utility of this method was readily elaborated by a gram-scale reaction, and synthetic transformations to other important chiral indolizine derivatives. Quantum mechanical explorations constructed a plausible synergetic catalytic cycle, revealed the origins of stereodivergence, and rationalized the protonation-stimulated stereoselective Friedel-Crafts type cyclization to form the indolizine products.

Biomechanical Properties of Novel Lateral Hole Pedicle Screws and Solid Pedicle Screws: A Comparative Study in the Beagle Dogs.

OBJECTIVE: Although pedicle screws are widely used to reconstruct the stability of the spine, screw loosening is a common complication after spine surgery. The main objective of this study was to investigate whether the application of the hollow lateral hole structure had the potential to improve the stability of the pedicle screw by comparing the biomechanical properties of the novel lateral hole pedicle screws (LHPSs) with those of the solid pedicle screws (SPSs) in beagle dogs. METHODS: The cancellous bone of the distal femur, proximal femur, distal tibia, and proximal tibia were chosen as implantation sites in beagle dogs. In each of 12 dogs, four LHPSs, and four SPSs were implanted into both lower limbs. At 1, 2, and 3 months after surgery, four dogs were randomly sampled and sacrificed. The LHPS group and SPS group were subdivided into four subgroups according to the length of their duration of implantation (0, 1, 2, 3 months). The biomechanical properties of both pedicle screws were evaluated by pull-out and the cyclic bending tests. RESULTS: The results of the study showed that no significant difference was found between LHPSs (276.62 ± 50.11 N) and SPSs (282.47 ± 42.98 N) in pull-out tests at time 0 (P > 0.05). At the same time point after implantations, LHPSs exhibited significantly higher maximal pullout strength than SPSs (month 1: 360.51 ± 25.63 vs 325.87 ± 28.11 N; month 2: 416.59 ± 23.78 vs 362.12 ± 29.27 N; month 3: 447.05 ± 38.26 vs 376.63 ± 32.36 N) (P < 0.05). Moreover, compared with SPSs, LHPSs withstood more loading cycles (month 2: 592 ± 21 vs 534 ± 48 times; month 3: 596 ± 10 vs 543 ± 59 times), and exhibiting less displacement before loosening at month 2 (1.70 ± 0.17 vs 1.96 ± 0.10 mm) and 3 (1.69 ± 0.19 vs 1.92 ± 0.14 mm) (P < 0.05), but no significant difference in time 0 and month 1 (P > 0.05). CONCLUSIONS: The pedicle screw with the hollow lateral hole structure could allow bone to grow into the inner architecture, which improved biomechanical properties by extending the contact area between screw and bone tissue after implantation into the cancellous bone. It indicated that LHPS could reduce loosening of the pedicle screws in long term after surgery.

Clinical characteristic and surgical treatment of traumatic lumbar spondylolisthesis: A series of 28 patients.

OBJECTIVE: To explore the clinical characteristics and the short-term efficacy of posterior operation for traumatic lumbar spondylolisthesis. METHODS: All 28 patients (between January 2013 and June 2018) were treated with lumbar pedicle screw fixation combined with posterior intervertebral fusion. The clinical data and imaging materials of these patients were retrospectively analyzed. RESULTS: The mean follow-up period was 24.3 months (12-36 months). The average VAS score and JOA score were significantly improved after surgery, and the difference was statistically significant (P<0.05).The last follow-up X-ray showed that 16 cases were degree 0 and 12 cases were degree I according to Meyerding grading, which were statistically improved compared with preoperative. Postoperative CT indicated lumbar internal fixation well, and the lumbar fusion rate was 100%. The Frankel grading of neurological function was significantly improved compared with preoperative. CONCLUSION: Acute traumatic lumbar spondylolisthesis is caused by severe trauma and mostly occurred at L4/L5 and L5/S1 level. Early posterior reduction, decompression and intervertebral fusion can achieve satisfactory clinical and radiological outcome.

Cu-Catalyzed Dehydrogenative Olefinsulfonation of Alkyl Arenes.

A copper-catalyzed reaction protocol for the dehydrogenation of ethylbenzenes into styrene derivatives has been developed. This reaction procedure proceeded well under mild reaction conditions, providing a practical and efficient strategy for the rapid assembly of biologically and pharmaceutically significant molecules, such as vinyl sulfone. Simple alkyl arenes were functionalized via consecutive ß-elimination in the presence of N-sulfonylbenzo[d]imidazole with broad substrate scope and good functional group tolerance.

Mapping the Scientific Research on Healthcare Workers' Occupational Health: A Bibliometric and Social Network Analysis.

In the last few years, the occupational health (OH) of healthcare workers (HCWs) has been shown increasing concern by both health departments and researchers. This study aims to provide academics with quantitative and qualitative analysis of healthcare workers' occupational health (HCWs+OH) field in a joint way. Based on 402 papers published from 1992 to 2019, we adopted the approaches of bibliometric and social network analysis (SNA) to map and quantify publication years, research area distribution, international collaboration, keyword co-occurrence frequency, hierarchical clustering, highly cited articles and cluster timeline visualization. In view of the results, several hotspot clusters were identified, namely: physical injuries, workplace, mental health; occupational hazards and diseases, infectious factors; community health workers and occupational exposure. As for citations, we employed document co-citation analysis to detect trends and identify seven clusters, namely tuberculosis (TB), strength training, influenza, healthcare worker (HCW), occupational exposure, epidemiology and psychological. With the visualization of cluster timeline, we detected that the earliest research cluster was occupational exposure, then followed by epidemiology and psychological; however, TB, strength training and influenza appeared to gain more attention in recent years. These findings are presumed to offer researchers, public health practitioners a comprehensive understanding of HCWs+OH research.

MiR-9 functions as a tumor suppressor in acute myeloid leukemia by targeting CX chemokine receptor 4.

MicroRNAs (miRNAs) play key roles in the pathogenesis of many cancers, including acute myeloid leukemia (AML). Although miRNA-9 (miR-9) is involved in the leukemogenesis of AML, the underlying mechanisms remain to be elucidated. In this study, we found that miR-9 and C-X-C chemokine receptor 4 (CXCR4) were differentially expressed in myeloid leukemia, particularly in AML. The inverse correlation between miR-9 and CXCR4 was identified in AML samples and cell lines. The AML patients simultaneously with high levels of CXCR4 and low expression of miR-9 possessed poor prognosis. In vitro, miR-9 inhibited the proliferation, apoptosis resistance, migration, and invasion of AML cells. Dual luciferase assays verified CXCR4 as a direct target of miR-9. The suppressive effects of miR-9 on AML cells were counteracted or mimicked by CXCR4 overexpression or depletion, respectively. Overall, this study reveals that miR-9 retards the aggressive behaviors of AML cells by repressing CXCR4. Thus, miR-9/CXCR4 axis may represent a potential therapeutic target for AML.

A Comparison Study of Three Posterior Fixation Strategies in Transforaminal Lumbar Interbody Fusion Lumbar for the Treatment of Degenerative Diseases.

BACKGROUND: There are various posterior fixations utilized with transforaminal lumbar interbody fusion (TLIF). Previous studies have focused on the comparison of two fixation techniques. MATERIALS AND METHODS: Sixty five patients with single-level lumbar disease were included in this retrospective study. Group A was treated by TLIF with bilateral pedicle screw (BPS), Group B treated by TLIF with unilateral pedicle screw (UPS), and Group C treated by TLIF with UPS plus contralateral translaminar facet screw (UPSFS). The operative time, blood loss, Oswestry disability index (ODI), Japanese Orthopaedic Association Scores (JOA), and visual analog scores (VAS) were recorded. Radiographic examination was used to assess fusion rates and incidence of screw failure. RESULTS: The blood loss and operative times were 188.69 ± 37.69 ml and 132.96.5 ± 8.69 min in BPS group, 117.27 ± 27.11 ml and 99.32 ± 12.94 min in UPS group, and 121.50 ± 22.54 ml and 112.55 ± 9.42 min in UPSFS group; UPS and UPSFS were better than BPS (P < 0.05). The mean followup time was 38.2 months. Fusion rates were - BPS group: 95.6%, UPS group: 90%, UPSFS: 95% (P > 0.05). Screw and/or rod failures were found in three groups (BPS group: 1, UPS group: 2 and UPSFS: 1, P > 0.05). The average postoperative VAS, ODI, and JOA scores of BPS, UPS, and UPSFS were improved significantly in each group compared to preoperative scores (P < 0.05); there were no significant differences between any two groups at each followup time point (P > 0.05). CONCLUSION: UPSFS with TLIF is a viable treatment option that provides satisfactory clinical results; the clinical outcome and the complication rate were comparable to BPS. In addition, the invasive of UPSFS cases was comparable to UPS and better than BPS cases. For UPS, it could be used in suitable patients.

A comparative study on the accuracy of pedicle screw placement assisted by personalized rapid prototyping template between pre- and post-operation in patients with relatively normal mid-upper thoracic spine.

PURPOSE: The aim of this study was to assess the accuracy of rapid prototyping drill template technique for placing pedicle screws in the mid-upper thoracic vertebrae in clinics. METHODS: 151 consecutive patients underwent thoracic instrumentation and fusion for a total of 582 pedicle screws placed in the mid-upper thoracic vertebrae. Using computer software, the authors constructed drill templates that fit onto the posterior elements of the mid-upper thoracic vertebrae with drill guides designed to instrument the pedicles. The start point and three dimensional location of the planned and inserted screws were measured and compared. RESULTS: Grading of the CT scans revealed 559 (96.1 %) out of 582 screws completely within the desired pedicle. The direction of pedicle violation included 5 medial, 2 airball, and 16 lateral. The paired t test suggested that these results were statistically significant in more than half of the locations (T1-left-TA(P = 0.024), T2-left-SA(P = 0.031), T3-left-SA(P = 0.014), T4-left-TA(P = 0.004), T5-left-TA(P = 0.034), T7-left-TA(P = 0.000). T1-right-TA(P = 0.049), T2-right-TA(P = 0.044), T3-right-TA(P = 0.014), T5-right-TA(P = 0.013)). The paired t-test suggested that these results were statistically significant at several locations (T4-left-Δy(P = 0.041), T5-left-Δx(P = 0.016), T3-right-Δy(P = 0.015)). CONCLUSION: Use of a rapid prototyping drill template to assist in the placement of mid and upper thoracic pedicle screws may lead to increased accuracy. This patient specific technology must be combined with an understanding of the patients' anatomy and carefully secured to the posterior elements intraoperatively to avoid nerve or vascular complications.

The LIM domain protein FHL1C interacts with tight junction protein ZO-1 contributing to the epithelial-mesenchymal transition (EMT) of a breast adenocarcinoma cell line.

FHL1C is a LIM domain protein that has been implied in transcription regulation through interacting with other proteins, such as RBP-J, the critical transcription factor of the Notch signaling pathway. The LIM domain is a protein-protein interaction interface, suggesting that FHL1C could bind other proteins to enable its functions. In order to explore the interacting proteins with FHL1C, in this study we screened FHL1C-interacting proteins by using immunoprecipitation and mass spectrometric analysis. ZO-1, a member of the Zonula occludens proteins that constitute tight junctions, was sorted out as one candidate by using these techniques. Furthermore, we confirmed the interaction between FHL1C and ZO-1 in cells by using the mammalian two-hybrid assay and the co-immunoprecipitation assay, and verified that ZO-1 could interact with FHL1C through the PDZ domains of ZO-1. Moreover, with immunofluorescence staining, we found that FHL1C could induce ZO-1 translocating into nucleus. With a breast adenocarcinoma cell line MCF7, we showed that the interaction between FHL1C and ZO-1 could contribute to the epithelial-mesenchymal transition (EMT). Taken together, our study might provide new insight into the function of FHL1C on the regulation of EMT in cancer cells.

Soluble extracellular domains of human SIRPα and CD47 expressed in Escherichia coli enhances the phagocytosis of leukemia cells by macrophages in vitro.

Signal regulatory protein (SIRP) α, a transmembrane protein belonging to the immunoglobulin superfamily, is a receptor for CD47. The interaction between SIRPα and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages. Here, we consider an alternative way to interrupt the interaction between CD47 and SIRPα. We expressed the extracellular domains of the human SIRPα (hSIRP(ext)) and the human CD47 (hCD47(ext)) in Escherichia coli as Trx fusion proteins, and purified them by using affinity chromatography. We show that the purified fusion protein Trx-SIRP(ext) could interact in vitro with Trx-hCD47(ext). Moreover, Trx-SIRP(ext) could effectively bind to Jurkat T-ALL cells, which expressed CD47 at a high level. CD47(ext), on the other hand, bound to human macrophages. In vitro phagocytosis assay showed that these fusion proteins could enhance the phagocytosis of Jurkat cells by macrophage, with Trx-hSIRP(ext) showed a higher efficiency than Trx-CD47(ext). These results indicated that the soluble Trx-hSIRP(ext) and Trx-CD47(ext) polypeptides could be alternative molecules to interrupt CD47-SIRPα interaction between leukemia cells and macrophages, and might be potentially useful for the targeted therapy of leukemia.