Revolutionizing medicine: Molecularly imprinted polymers as precision tools in cancer diagnosis and antibiotic detection.

Molecularly imprinted polymers (MIPs) are pivotal in medicine, mimicking biological receptors with enhanced specificity and affinity. Comprising templates, functional monomers, and cross-linkers, MIPs form stable three-dimensional polymer networks. Synthetic templates like glycan and aptamers improve efficiency, guiding the molecular imprinting process. Cross-linking determines MIPs' morphology and mechanical stability, with printable hydrogels offering biocompatibility and customizable properties, mimicking native extracellular matrix (ECM) microenvironments. Their versatility finds applications in tissue engineering, soft robotics, regenerative medicine, and wastewater treatment. In cancer research, MIPs excel in both detection and therapy. MIP-based detection systems exhibit superior sensitivity and selectivity for cancer biomarkers. They target nucleic acids, proteins, and exosomes, providing stability, sensitivity, and adaptability. In therapy, MIPs offer solutions to challenges like multidrug resistance, excelling in drug delivery, photodynamic therapy, photothermal therapy, and biological activity regulation. In microbiology, MIPs serve as adsorbents in solid-phase extraction (SPE), efficiently separating and enriching antibiotics during sample preparation. They contribute to bacterial identification, selectively capturing specific strains or species. MIPs aid in detecting antibiotic residues using fluorescent nanostructures and developing sensors for sulfadiazine detection in food samples. In summary, MIPs play a pivotal role in advancing medical technologies with enhanced sensitivity, selectivity, and versatility. Applications range from biomarker detection to innovative cancer therapies, making MIPs indispensable for the accurate determination and monitoring of diverse biological and environmental samples.

Protective effects of polydatin against bone and joint disorders: the in vitro and in vivo evidence so far.

Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recent in vivo and in vitro progress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesis in vitro, and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account.

Extracellular vesicles from human umbilical cord mesenchymal stem cells reduce lipopolysaccharide-induced spinal cord injury neuronal apoptosis by mediating miR-29b-3p/PTEN.

OBJECTIVE: This study investigated the molecular mechanism of whether hUC-MSCs-EVs repressed PTEN expression and activated the PI3K/AKT pathway through miR-29b-3p, thus inhibiting LPS-induced neuronal injury. METHODS: hUC-MSCs were cultured and then identified. Cell morphology was observed. Alizarin red, oil red O, and alcian blue staining were used for inducing osteogenesis, adipogenesis, and chondrogenesis. EVs were extracted from hUC-MSCs and identified by transmission electron microscope observation and Western blot. SCI neuron model was established by 24h lipopolysaccharide (LPS) induction. After the cells were cultured with EVs without any treatment, uptake of EVs by SCI neurons, miR-29b-3p expression, cell viability, apoptosis, caspase-3, cleaved caspase-3, caspase 9, Bcl-2, PTEN, PI3K, AKT, and p-Akt protein levels, caspase 3 and caspase 9 activities, and inflammatory factors IL-6 and IL-1ß levels were detected by immunofluorescence labeling, RT-qPCR, MTT, flow cytometry, Western blot, caspase 3 and caspase 9 activity detection kits, and ELISA. The binding sites between PTEN and miR-29b-3p were predicted by the database and verified by dual-luciferase assay. RESULTS: LPS-induced SCI cell model was successfully established, and hUC-MSCs-EVs inhibited LPS-induced apoptosis of injured spinal cord neurons. EVs transferred miR-29b-3p into LPS-induced injured neurons. miR-29b-3p silencing reversed EV effects on reducing LPS-induced neuronal apoptosis. miR-29b-3p reduced LPS-induced neuronal apoptosis by targeting PTEN. After EVs-miR-inhi and si-PTEN treatment, inhibition of the PI3K/AKT pathway reversed hUC-MSCs-EVs effects on reducing LPS-induced neuronal apoptosis. CONCLUSION: hUC-MSCs-EVs activated the PI3K/AKT pathway by carrying miR-29b-3p into SCI neurons and silencing PTEN, thus reducing neuronal apoptosis.

A comparison of three bone graft struts for interbody fusion using a posterior approach for lower lumbar spinal tuberculosis in adults: a midterm follow-up study.

BACKGROUND: This retrospective observational study was conducted to compare midterm outcomes of three bone graft struts for interbody fusion using a posterior approach in adults with lower lumbar spinal tuberculosis. METHODS: A total of 126 lower lumbar spinal tuberculosis patients were treated by one-stage posterior debridement, interbody fusion, and instrumentation. Forty-one patients (group A) were treated with autogenous bone graft for interbody fusion, 45 patients (group B) were treated with allogeneic bone grafting, and the remaining 40 (group C) patients were treated with titanium mesh cage. In addition, clinical and radiographic data were gathered and analyzed. RESULTS: At the final follow-up, all patients were completely cured. The operation period and intraoperative blood loss for groups B and C were significantly less than in group A (P = 0.000). Post-operation, neurological performance and quality of life were remarkably improved at the final follow-up. The preoperative lordosis angles of three groups were significantly improved, as evidenced by the values immediately after the operation or those at the final follow-up. The correction loss of the group C was lower than those of groups A and B (P = 0.000). All the patients obtained bone graft fusion, the fusion period of group B was longer than that of the other two groups (P = 0.000). No significant differences among the three groups in adjacent segment degeneration rates were found at the last visit (P = 0.922). CONCLUSIONS: This midterm follow-up study established that one-stage posterior debridement, interbody fusion, and instrumentation, combined with medical therapy, can effectively treat lower lumbar spinal tuberculosis. In addition, the intervertebral titanium mesh cage bone graft can provide better outcomes with regard to maintaining lordosis and preventing collapse.

Endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion for the treatment of upper cervical spine tuberculosis: a retrospective feasibility study.

BACKGROUND: This retrospective study aimed to determine the feasibility and efficacy of endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion in patients with upper cervical spine tuberculosis. METHODS: Between June 2008 and January 2016, 17 patients (10 men and 7 women) with upper cervical spine tuberculosis underwent endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion. Anti-tuberculosis treatment was administered for 2-4 weeks preoperatively and 12-18 months postoperatively. The clinical and radiographic data of the patients were analyzed. RESULTS: The operation was successfully completed in all patients. Neck pain and stiffness were relieved after the surgery in all patients. The mean operation time was 210.0 ± 21.2 min, and the mean intraoperative blood loss was 364.7 ± 49.6 mL. The mean follow-up duration was 68.1 ± 6.7 months. The erythrocyte sedimentation rate returned to normal by 3 months postoperatively. Visual analog scale scores for neck pain were significantly lower postoperatively than preoperatively. All patients had significant postoperative neurological improvement. Patient-reported outcomes, as measured using the Kirkaldy-Willis criteria, were as follows: excellent, 12 patients; good, 4 patients; fair, 1 patient; and poor, 0 patients. Bone fusion was achieved at 10.9 ± 1.9 months after the surgery; no cases of instrument loosening or fracture occurred. CONCLUSION: Endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion is a feasible and effective surgical method for the treatment of upper cervical spine tuberculosis. It can be used to restore upper cervical spine stability and facilitate spinal healing.

Early surgical intervention for active thoracic spinal tuberculosis patients with paraparesis and paraplegia.

BACKGROUND: To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia. METHODS: Data on 118 active thoracic spinal TB patients with paraparesis and paraplegia who had undergone surgery at an early stage (within three weeks of paraparesis and paraplegia) from January 2008 to December 2014 were retrospectively analyzed. The operation duration, blood loss, perioperative complication rate, VAS score, ASIA grade and NASCIS score of neurological status rating, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb's angle, and duration of bone graft fusion were analyzed to evaluate the therapeutic effects of surgery. RESULTS: The mean operating time was 194.2 minutes, and the mean blood loss was 871.2 ml. The perioperative complication rate was 5.9 %. The mean preoperative VAS score was 5.3, which significantly decreased to 3.2 after the operation and continued decreasing to 1.1 at follow up (P<0.05). All cases achieved an increase of at least one ASIA grade after operation. The rate of full neurological recovery for paraplegia (ASIA grade A and B) was 18.0 % and was significantly lower than the rate (100 %) for paraparesis (ASIA grade C and D) (P<0.05). On the NASCIS scale, the difference in the neurological improvement rate between paraplegia (22.2 % ± 14.1 % in sensation and 52.2 % ± 25.8 % in movement) and paraparesis (26.7 % ± 7.5 % in sensation and 59.4 % ± 7.3 % in movement) was remarkable (P<0.05). Mean preoperative ESR and CRP were 73.1 mm /h and 82.4 mg/L, respectively, which showed a significant increase after operation (P>0.05), then gradually decreased to 11.5 ± 1.8 mm/h and 2.6 ± 0.82 mg/L, respectively, at final follow up (P<0.05). The mean preoperative kyphotic Cobb's angle was 21.9º, which significantly decreased to 6.5º after operation (P<0.05) while kyphotic correction was not lost during follow up (P>0.05). The mean duration of bone graft fusion was 8.6 ± 1.3 months. CONCLUSIONS: Early surgical intervention may be beneficial for active thoracic spinal TB patients with paraparesis and paraplegia, with surgical intervention being more beneficial for recovery from paraparesis than paraplegia.

Matrix metalloproteinases-9 deficiency impairs liver regeneration through epidermal growth factor receptor signaling in partial hepatectomy mice.

BACKGROUND: Liver regeneration is a complex process regulated by many complex mechanisms involving cytokines, growth factors, metabolic networks, and so forth. Previous investigations have demonstrated that matrix metalloproteinase-9 (MMP-9) is an essential factor in liver regeneration. The present study aimed to explore the role of MMP-9 in epidermal growth factor receptor (EGFR) signaling and related proliferation signaling factors in a mouse partial hepatectomy (PH) model. MATERIALS AND METHODS: MMP-9 knockout (KO) and wild-type mice were used to establish the PH model. Liver regeneration was analyzed based on proliferation cell nuclear antigen immunohistochemistry and liver weight to body weight ratio. Also, EGFR ligands, EGFR, and downstream factors were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot. RESULTS: MMP-9 KO mice showed a delayed hepatic regenerative response after PH. EGFR ligands, including heparin-binding epidermal growth factor and amphiregulin, were expressed at significantly lower levels between days 1 and 3 posthepatectomy in MMP-9 KO mice. MMP-9 KO mice also inhibited and delayed EGFR activation after PH. After PH, the expression of STAT3, NF-κB, and cyclinD1, all downstream of EGFR, was similar to EGFR activation. CONCLUSIONS: Our data provide new evidence supporting a critical role of MMP-9 in liver regeneration after PH through activation of EGFR signaling.

Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats.

BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia-reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS: Male Sprague-Dawley rats (8-10 weeks) were randomly divided into the control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days. RESULTS: Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P<0.01, 0.01 and 0.05, respectively) and oxidative indices (P<0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine), more severe liver damage (P<0.01) and up-regulated ER stress signal expressions (P<0.01 for GRP78, phos-eIF2alpha1, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12). All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels (P<0.05), increased superoxide dismutase activities (P<0.01), alleviated liver damage (P<0.01), down-regulated ER stress signal expressions (P<0.01) and improved postoperative survivals (P<0.01). CONCLUSIONS: ER stress was involved with DCD liver transplantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.

Long-segment versus short-segment fixation through a posterior approach for tuberculous spondylodiscitis of the mid-thoracic spine in adults: a study of mid- to long-term efficacy.

BACKGROUND: This retrospective study aimed to perform a comparative evaluation of the mid- to long-term efficacy of long-segment and short-segment fixations via the posterior approach as a treatment for tuberculous spondylodiscitis in the mid-thoracic spine. METHODS: A total of 95 patients with tuberculous spondylodiscitis in the mid-thoracic spine underwent surgery via the posterior approach including single-stage posterior debridement, interbody fusion, and pedicle screw fixation. Long-segment fixations were performed for 46 patients (group A), while short-segment fixations were performed for the other 49 patients (group B). Clinical and radiological outcomes were assessed during mid- to long-term follow-up. RESULTS: The average follow-up periods for groups A and B were 75.5±11.8 and 76.8±11.6 months, respectively. The operative time and intraoperative blood loss were lower in group B than in group A (P<0.05). Both management approaches significantly corrected the kyphotic deformity detected either in the early postoperative period or at the final visit after long-term follow-up (P>0.05). Bony fusion was generated after average periods of 10.8±2.1 months and 11.0±2.0 months in groups A and B, respectively. Favorable outcomes were observed on assessment of neurological function and patients' well-being at the final follow-up. CONCLUSIONS: No therapeutic differences were observed between long-segment and short-segment fixation as surgical treatment for mid-thoracic Pott's disease during mid- to long-term follow-up. Kyphotic deformity and neurological impairment were significantly relieved via both posterior fixation approaches, with patients' well-being reaching a favorable level. Moreover, short-segment fixation led to less blood loss and required a shorter operative time.

An innovative parameter optimization of Spark Streaming based on D3QN with Gaussian process regression.

Nowadays, Spark Streaming, a computing framework based on Spark, is widely used to process streaming data such as social media data, IoT sensor data or web logs. Due to the extensive utilization of streaming media data analysis, performance optimization for Spark Streaming has gradually developed into a popular research topic. Several methods for enhancing Spark Streaming's performance include task scheduling, resource allocation and data skew optimization, which primarily focus on how to manually tune the parameter configuration. However, it is indeed very challenging and inefficient to adjust more than 200 parameters by means of continuous debugging. In this paper, we propose an improved dueling double deep Q-network (DQN) technique for parameter tuning, which can significantly improve the performance of Spark Streaming. This approach fuses reinforcement learning and Gaussian process regression to cut down on the number of iterations and speed convergence dramatically. The experimental results demonstrate that the performance of the dueling double DQN method with Gaussian process regression can be enhanced by up to 30.24%.

Comparing Bone Graft Techniques for Interbody Fusion through a Posterior Approach for Treating Mid-Thoracic Spinal Tuberculosis: A Retrospective Analysis.

OBJECTIVE: Mid-thoracic spinal tuberculosis is prone to kyphotic deformities and neurologic impairment. Posterior approach can effectively restore the spinal stability by reconstructing the anterior and middle spinal columns. Titanium mesh cages (TMC), allogeneic bone (ALB), and autogenous bone (AUB) are three main bone graft struts. We aimed to compare the therapeutic efficacy of three bone graft struts, for anterior and middle column reconstruction through a posterior approach in cases of mid-thoracic spinal tuberculosis. METHODS: Hundred and thirty seven patients with thoracic spinal tuberculosis who had undergone a posterior approach from June 2010 to December 2018 were enrolled. Of them, 46 patients were treated using a titanium mesh cage (TMC group), 44 with allogenic bone grafts (ALB group), and 47 using autogenous bone grafts (AUB group). The following were analyzed to evaluate clinical efficacy: visual analogue scale (VAS) values, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, kyphotic Cobb's angle, operation duration, intraoperative blood loss, improvement in American Spinal Injury Association (ASIA) grade and in the mental component summary (MCS) and physical component summary (PCS) of Short Form-36 (SF-36), duration of bone graft fusion. The data of the three groups were compared by way of variance analysis, followed by the LSD⁃t test to compare each group. A repeated measures ANOVA was used to analyze the dates of pre-, postoperative and final follow-up. RESULTS: The follow-up duration was at least 3 years. All patients achieved a complete cure for spinal TB. Neurological performance and quality of life were remarkably improved at the final follow-up. The intraoperative blood loss, operation time and VAS values 1 day postoperatively for TMC group and ALB group were significantly lower than those in AUB group (P < 0.05). The duration of bone graft fusion in ALB group (18.1 ± 3.7 months) was longer than that in TMC group and AUB group (9.5 ± 2.8 and 9.2 ± 1.9 months) (P < 0.05). No significant intergroup differences were observed in terms of age or preoperative, 3-months postoperative, and final follow-up indices of ESR and CRP among the three groups (P > 0.05). At the final follow-up, the correction loss was mild (2.1 ± 0.9, 2.2 ± 1.0, 2.1 ± 0.8) and Cobb's angles of the three groups were 20.1 ± 2.9, 20.5 ± 3.2, 20.9 ± 3.4, respectively, which were remarkably rectified in comparison with the preoperative measurements (P < 0.05). CONCLUSIONS: In terms of postoperative recovery and successful fusion rate of bone graft, it seems that posterior instrumentation, debridement, and interbody fusion with titanium mesh cages are more effective and appropriate surgical methods for mid-thoracic spinal tuberculosis.

TransUFold: Unlocking the structural complexity of short and long RNA with pseudoknots.

The RNA secondary structure is like a blueprint that holds the key to unlocking the mysteries of RNA function and 3D structure. It serves as a crucial foundation for investigating the complex world of RNA, making it an indispensable component of research in this exciting field. However, pseudoknots cannot be accurately predicted by conventional prediction methods based on free energy minimization, which results in a performance bottleneck. To this end, we propose a deep learning-based method called TransUFold to train directly on RNA data annotated with structure information. It employs an encoder-decoder network architecture, named Vision Transformer, to extract long-range interactions in RNA sequences and utilizes convolutions with lateral connections to supplement short-range interactions. Then, a post-processing program is designed to constrain the model's output to produce realistic and effective RNA secondary structures, including pseudoknots. After training TransUFold on benchmark datasets, we outperform other methods in test data on the same family. Additionally, we achieve better results on longer sequences up to 1600 nt, demonstrating the outstanding performance of Vision Transformer in extracting long-range interactions in RNA sequences. Finally, our analysis indicates that TransUFold produces effective pseudoknot structures in long sequences. As more high-quality RNA structures become available, deep learning-based prediction methods like Vision Transformer can exhibit better performance.

Comparison of two surgical interventions for lumbar brucella spondylitis in adults: a retrospective analysis.

This retrospective study aimed to compare the clinical efficacy of the posterior procedure with the combined anterior and posterior procedure in the surgical management of lumbar Brucella spondylitis. From January 2015 to June 2020, a total of 62 patients presenting with lumbar Brucella spondylitis underwent either one-stage posterior pedicle fixation, debridement, and interbody fusion (Group A, n = 33) or anterior debridement, bone grafting, and posterior instrumentation (Group B, n = 29). All patients were followed up for an average of 25.4 ± 1.5 months and achieved complete resolution of lumbar Brucella spondylitis. No significant differences between the groups were observed in terms of age or pre-operative, three-month postoperative and final follow-up indices of the VAS, ESR, CRP, lordosis angle, ODI scores, fusion time, and time of serum agglutination test conversion to negative (P > 0.05). Each patient exhibited notable improvements in neurological function, as assessed by the JOA score rating system. Group A demonstrated significantly shorter operative duration, intraoperative blood loss, and hospital stay compared to Group B (P < 0.05). Superficial wound infection was observed in one case in Group A, whereas Group B experienced one case each of intraoperative peritoneal rupture, postoperative ileus, iliac vein injury, and superficial wound infection. This study supports the efficacy of both surgical interventions in the treatment of lumbar Brucella spondylitis, with satisfactory outcomes. However, the posterior approach demonstrated advantages, including reduced surgical time, diminished blood loss, shorter hospital stays, and fewer perioperative complications. Consequently, the one-stage posterior pedicle fixation, debridement, and interbody fusion represent a superior treatment option.

Comparison of two surgical interventions for advanced stages pubis and pubic symphysis tuberculosis in adults: A retrospective study of 33 cases.

PURPOSE: To compare the clinical efficacy of two surgical interventions in treating advanced stages TB of the pubis and pubic symphysis. METHODS: Between June 2010 and January 2020, 33 cases of the advanced pubis and pubic symphysis TB were treated with a one-stage debridement procedure (debridement only group, n = 15) or a one-stage debridement with bone grafting and plate fixation procedure (debridement + plating group, n = 18). The visual analog scale (VAS) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), operation time, intraoperative blood loss, complications, time of bone graft fusion, and improvement in the mental component summary (MCS) and physical component summary (PCS) of Short Form-36 (SF-36) were compared and analyzed. RESULTS: All patients were followed for 24.9 (SD 1.6) months. All patients were completely cured of the pubis and pubic symphysis TB with no recurrence. There were no significant differences (P >0.05) between the two groups in terms of age, follow-up period and intraoperative blood loss. The post-operative VAS scores, ESR and CRP levels, PCS and MCS scores of two groups significantly improved compared to pre-therapy. The mean operation time in debridement + plating group was 140.9 (43.2) min, which was significantly longer than in debridement only group [94.9(21.8) min, P < 0.01]. The final follow-up (FFU) indices of the VAS score in debridement only group were higher than those in debridement + plating group [1.9 (0.8) vs 1.3 (0.5), P=0.012]. A satisfactory average bony fusion time of 12.2 (3.3) months was achieved in debridement + plating group . CONCLUSIONS: A one-stage debridement, bone grafting, and reconstruction plate fixation procedure achieved reconstruction of the integrity and stability of the pelvic ring, pain relief, and rapid cure of bone TB. This procedure is a safe and effective treatment option for advanced pubis and pubic symphysis TB.

Posterior transforaminal debridement and interbody fusion with instrumentation for multi-segment thoracic spinal tuberculosis: a midterm follow-up study.

This retrospective study aimed to evaluate midterm outcomes of surgical management of multi-segment thoracic spinal tuberculosis by single-stage posterior transforaminal debridement and interbody fusion with instrumentation. From January 2007 to October 2015, 42 adult patients with thoracic spinal tuberculosis involving three or more levels underwent single-stage posterior transforaminal debridement, interbody fusion and instrumentation At a mean follow-up of 73.5 ± 9.6 months, all patients were eligible for final evaluation. All displayed improved biochemical markers and pain scores at 3 months and improved physiologic levels at the end of treatment. Visual analogue and 36-Item Short-Form Health Survey scores were significantly improved compared with preoperative values. All 30 patients with preoperative neurological deficits experienced neurologic improvement. Thoracic kyphosis angle decreased significantly from 34.4° ± 4.5° to 22.0° ± 2.6°. A mean kyphotic angle loss of 1.7° ± 1.1° was recorded at the final follow-up, and bone fusion was observed at a mean of 10.6 ± 2.1 months, with no instrumentation failures. One patient experienced delayed incisional healing and five patients suffered postoperative intercostal neuralgia that were cured by conservative treatment. There were no graft failures or implant breakages. This study showed the utility of a single-staged procedure combining posterior transforaminal debridement and interbody fusion with instrumentation, and demonstrated promising results.

Macrophage responses to selective laser-melted Ti-6Al-4V scaffolds of different pore geometries and the corresponding osteoimmunomodulatory effects toward osteogenesis.

Following recent advances in osteoimmunology, there is growing recognition of the vital role of immune cells in the osteogenesis process. The 3D-printed scaffold, as a substitute for injured and/or diseased bone tissues, has demonstrated satisfactory pro-osteogenetic performance. However, whether immune cells prompt the above pro-osteogenetic performance has not been elucidated in detail. In the present study, highly controllable Ti-6Al-4V scaffolds with different pore geometries were fabricated using a selective laser-melting technique, to reveal their osteoimmunological functions with macrophages. The results showed that macrophages displayed characteristics of M2 phenotype in response to scaffolds. As a result, an anti-inflammatory microenvironment was generated. When the pore geometry was considered, such observations were more apparent with the hexagonal pore scaffold than with the triangular one. In addition, inhibition of the toll-like receptor signaling pathway in macrophages has been proposed to cause the above phenomenon. Upon applying conditioned media derived from macrophages on pre-osteoblasts, the hexagonal pore scaffold group was found to significantly enhance osteoblastic differentiation, via macrophage-to-implant interactions. However, the effect of triangular pore scaffold was not statistically significant compared to that of hexagonal pore scaffolds or nonporous samples. In an attempt to quantify scaffold pore geometries, it was suggested that pores with higher circularity values tended to induce M2 polarization of macrophages, promote an anti-inflammatory milieu, and therefore, achieve better osteogenetic performance via immunomodulation.

Preparation and Biocompatibility of Core-Shell Microspheres for Sequential, Sustained Release of BMP-2 and VEGF.

Bone defect repair remains a challenge in orthopedics. This study describes the development and potential effectiveness of vascular endothelial growth factor (VEGF)/bone morphogenetic protein-2 (BMP-2) shell-core microspheres for promoting bone regeneration. Poly(L-lactic acid)/polylactic-co-glycolic acid (PLLA/PLGA) core-shell microspheres loaded with VEGF and BMP-2 were prepared by a coaxial electrospray technique, and their surface morphology, core-shell distribution, and particle size were examined. Different groups of microspheres were prepared with different placement of the growth factors, and the encapsulation efficiency and in vitro release curves were measured. Additionally, the effects of the different groups of microspheres on the proliferation and differentiation of osteoblasts and vascular endothelial cells were investigated. The prepared microspheres had a core-shell structure with good homogeneity and dispersion, a clear boundary, and a smooth surface. On scanning electron microscopy, the mean diameter of the microspheres was similar for all six preparations (P > 0.05). During in vitro release, growth factor was initially released via a brief burst release from the outer shell of the microsphere followed by a slower sustained release. The release of growth factors from the inner core remained relatively slow and sustained. Sequential release of different growth factors was achieved through the inconsistent release rates from the microsphere shell and inner core. All groups of microspheres showed no cytotoxicity, good biocompatibility, and the ability to promote osteoblast proliferation. The microspheres loaded with BMP-2 also promoted osteoblast differentiation, and VEGF-loaded microspheres promoted the proliferation and differentiation of vascular endothelial cells. The BMP-2 (core)/VEGF (shell) microsphere group best promoted osteoblast differentiation. The microspheres prepared in this study exhibited slow sequential release of BMP-2 and VEGF and showed good biocompatibility along with the ability to promote osteoblast differentiation and vascular endothelial cell proliferation.

Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system.

The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro. Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo. The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation (p < 0.05) compared to pure titanium alloy scaffolds in vitro. Furthermore, the composite scaffold can exhibit significant osteogenic differentiation (p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds (p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups (p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration.

In Vitro and In Vivo Analysis of the Effects of 3D-Printed Porous Titanium Alloy Scaffold Structure on Osteogenic Activity.

The effect of titanium scaffold geometry on the bone regeneration ability of the scaffold remains unclear. Here, selective laser melting as a 3D printing technology was used to create porous titanium alloy scaffolds with two unit structures: a hollow hexagonal prism (group A) and a hollow triangular prism (group B). The structures and morphologies of the scaffolds were characterized before mechanical properties were simulated. Cell adhesion behaviors, osteoblast activity and proliferation, and alkaline phosphatase (ALP) activity were evaluated, in addition to in vivo testing in an animal model. The results showed that the two scaffolds made of Ti6Al4V had compression moduli similar to that of human cortical bone (116.91 ± 0.01 and 174.29 ± 2.21 MPa vs. 89-164 MPa). The two scaffolds were nontoxic to cells and had good biocompatibility, while group A scaffolds facilitated cell adhesion. The number of cells increased gradually in culture. The ALP activity of cells on group A scaffolds demonstrated higher osteogenic ability than that of group B scaffolds. The in vivo tests showed that all scaffolds retained their shape well after implantation, and no obvious inflammatory reaction or infection in surrounding tissues was found. Based on fluorescence staining, mature new bone formation was found at week 12. Group A scaffolds showed better bone integration ability compared with group B scaffolds. The percentage of new bone area in group A (7.5%) was higher than that in group B (6.5%). This research suggests that the hollow hexagonal prism structure of porous scaffolds can promote osteogenic differentiation and osseointegration better than the triangular prism structure.

Long non-coding RNA GAS6-AS1 enhances breast cancer cell aggressiveness by functioning as a competing endogenous RNA of microRNA-215-5p to enhance SOX9 expression.

Long non-coding (lnc) RNAs play crucial functions in human cancer. However, until recently, the involvement of the lncRNA GAS6-AS1 in breast cancer (BCa) malignancy has not been studied exhaustively. The roles and underlying mode of action of GAS6-AS1 action in BCa progression were examined through functional experiments. A decline in GAS6-AS1 level led to a significant decrease in BCa cell proliferation, and the ability for colony formation. Here, GAS6-AS1 competed as endogenous RNA by sequestering microRNA-215-5p (miR-215-5p) causing an enhanced expression of SRY-box transcription factor 9 (SOX9). The effects of silencing GAS6-AS1 on BCa malignant phenotypes could be ameliorated by inhibiting miR-215-5p or restoring SOX9. Thus, GAS6-AS1 acted as a lncRNA that drives tumor in BCa, and enabled progression of BCa through miR-215-5p /SOX9 axis regulation. These outcomes show that the GAS6-AS1/miR-215-5p/SOX9 axis is a potentially effective target for cancer treatment and management.