Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial.

Background: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. Methods: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. Interpretation: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. Funding: The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.

Nicotinamide phosphoribose transferase facilitates macrophage-mediated pulmonary fibrosis through the Sirt1-Smad7 pathway in mice.

Pulmonary fibrosis is a challenging lung disease characterized by a bleak prognosis. A pivotal element in the progression of this disease is the dysregulated recruitment of macrophages. Nicotinamide phosphoribose transferase (NAMPT), secreted by alveolar epithelial cells and inflammatory cells, has been previously identified to influence macrophage inflammation in acute lung injury through the nicotinamide adenine dinucleotide (NAD) rescue synthesis pathway. Nonetheless, the exact role of NAMPT in the regulation of lung fibrosis is yet to be elucidated. In our research, we employed bleomycin (BLM) to induce pulmonary fibrosis in Namptflox/flox;Cx3cr1CreER mice, using Namptflox/flox mice as controls. Our findings revealed an augmented expression of NAMPT concurrent with a marked increase in the secretion of NAD and inflammatory cytokines such as IL-6, TNF-α, and TGF-ß1 post-BLM treatment. Furthermore, an upsurge in NAMPT-positive macrophages was observed in the lungs of BLM-treated Namptflox/flox mice. Notably, a conditional knockout of NAMPT (NAMPT cKO) in lung macrophages curtailed the BLM-induced inflammatory responses and significantly mitigated pulmonary fibrosis. This was associated with diminished phospho-Sirt1 (p-Sirt1) expression levels and a concomitant rise in mothers against decapentaplegic homolog 7 (Smad7) expression in BLM-treated mouse lungs and murine RAW 264.7 macrophage cells. Collectively, our data suggests that NAMPT exacerbates macrophage-driven inflammation and pulmonary fibrosis via the Sirt1-Smad7 pathway, positioning NAMPT as a promising therapeutic target for pulmonary fibrosis intervention.

Splenic proteome profiling in response to Marek's disease virus strain GX0101 infection.

Marek's disease virus (MDV) strain GX0101 was the first reported field strain of recombinant gallid herpesvirus type 2 (GaHV-2). However, the splenic proteome of MDV-infected chickens remains unclear. In this study, a total of 28 1-day-old SPF chickens were intraperitoneally injected with chicken embryo fibroblast (CEF) containing 2000 PFU GX0101. Additionally, a control group, consisting of four one-day-old SPF chickens, received intraperitoneal equal doses of CEF. Blood and various tissue samples were collected at different intervals (7, 14, 21, 30, 45, 60, and 90 days post-infection; dpi) for histopathological, real-time PCR, and label-free quantitative analyses. The results showed that the serum expressions of MDV-related genes, meq and gB, peaked at 45 dpi. The heart, liver, and spleen were dissected at 30 and 45 dpi, and their hematoxylin-eosin staining indicated that virus infection compromised the normal organizational structure at 45 dpi. Particularly, the spleen structure was severely damaged, and the lymphocytes in the white medulla were significantly reduced. Furthermore, liquid chromatography-mass spectrometry (LC-MS) and label-free techniques were used to analyze the difference in splenic proteome profiles of the experimental and control groups at 30 and 45 dpi. Proteomic analysis identified 1660 and 1244 differentially expressed proteins (DEPs) at 30 and 40 dpi, respectively, compared with the uninfected spleen tissues. According to GO analysis, these DEPs were involved in processes such as organelle organization, cellular component biogenesis, cellular component assembly, anion binding, small molecule binding, metal ion binding, cation binding, cytosol, nuclear part, etc. Additionally, KEGG analysis indicated that the following pathways were linked to MDV-induced inflammation, apoptosis, and tumor: Wnt, Hippo, AMPK, cAMP, Notch, TGF-ß, PI3K-Akt, Rap1, Ras, Calcium, NF-κB, PPAR, cGMP-PKG, Apoptosis, VEGF, mTOR, FoxO, TNF, JAK-STAT, MAPK, Prion disease, T cell receptor, and B cell receptor. We finally screened 674 DEPs that were linked to MDV infection in spleen tissue. This study improves our understanding of the MDV response mechanism in the spleen.

MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

Diabetes-related Screw Loosening: The Distinction of Surgical Sites and the Relationship among Diabetes, Implant Stabilization and Clinical Outcomes.

OBJECTIVES: Diabetes mellitus (DM) is correlated with poor clinical outcomes in spinal surgery. However, the effect of it on screw stabilization has not been investigated. The aim of this study was to evaluate the screw loosening rate and postoperative outcomes in diabetic patients and to identify potential risk factors associated with loosening. METHODS: This was a retrospective study. Two hundred and forty-three patients who received cervical or lumbar internal fixation between 2015 and 2019 were enrolled. Screw loosening was assessed on radiography, and clinical outcomes were evaluated by the improvement of visual analogue scale (VAS), Oswestry disability index (ODI) or Japanese Orthopaedic Association (JOA) scores. The relationship of DM, screw loosening and clinical outcomes were analyzed with chi-square tests and regression analyses. RESULTS: One hundred and twenty-two patients (50.2%) with diabetes were included in this study. Diabetes led to the increase of the rate of screw loosening in the lumbar spine, while the loosening rate did not vary significantly in the cervical spine. The occurrence of screw loosening in the lumbar spine was more likely to be associated with clinical outcomes for motor performance including walking and sitting. However, no significant effect on JOA and VAS scores in the cervical spine of screw loosening was found. Moreover, the history of DM affected the outcomes of the patients who underwent spinal surgery. CONCLUSION: DM had an adverse effect on screw stabilization. The impaired improvement of clinical outcomes in diabetics after spinal surgery was related to screw loosening. In addition to the direct effects on operative wounds and neural function, the impact on the screws due to DM was also worth noting.

Study on the poly(methyl methacrylate-acrylic acid)/calcium phosphate cement composite bound by chelation with enhanced water absorption and biomechanical properties.

Polymethylmethacrylate (PMMA) bone cement has been widely used as a critical material for fixing prostheses and filling bone defects. The shrinkage of PMMA bone cement was addressed by the additives, however, the uneven integral water absorption and expansion performance as well as the deteriorated mechanical properties of the modified bone cement after immersion in phosphate buffered saline (PBS) and simulation body fluid (SBF) affected the long-term stability after implantation. Calcium phosphate cement (CPC) is a biomaterial with promising applications in orthopedics, whose hydration reaction provides an important driving force for the transfer of water. Besides, the mechanical properties of CPC can be enhanced with the curing process. In this study, CPC was utilized to modify the poly(methyl methacrylate-acrylic acid) [P(MMA-AA)] bone cement. The results demonstrated the successful construction of interconnected CPC water delivery networks in the P(MMA-AA)/CPC composite, the water absorption ratio and expansion ratio of the composite were up to 131.18 ± 9.14% and 168.19 ± 5.44%, respectively. Meanwhile, the transformation of CPC water delivery networks into rigid mechanical support networks as well as the chelation interaction between organic-inorganic enhanced the mechanical properties of the composite after immersion, the compressive strength after immersion reached 62.97 ± 0.97 MPa, which was 27.65% higher than that before immersion. The degradation ratio of the composite was up to 13.76 ± 0.23% after 9 days of immersion, which was 16.4% higher than that of CPC. Furthermore, composites exhibited superior biocompatibility as the release of Ca2+. Therefore, P(MMA-AA)/CPC composite serves as a promising medical filling material for clinical use.

Paravertebral vs Epidural Anesthesia for Video-assisted Thoracoscopic Surgery: A Randomized Trial.

BACKGROUND: The choice of postoperative pain management for patients who experience moderate to severe acute pain after thoracoscopic surgery is debatable. This study aimed to determine whether paravertebral block (PVB) provides more benefits than thoracic epidural analgesia (TEA) for thoracoscopic surgery. METHODS: From February 2020 to April 2022, patients without chronic pain who were scheduled to undergo thoracoscopic surgery were randomly assigned to the PVB group or the TEA group. The visual analogue scale score was used to measure the degree of pain when the patients were at rest or coughing. RESULTS: In total, 176 eligible patients were enrolled in this study. No significant difference in the visual analogue scale score was found between the 2 groups at rest (P = .395) or with coughing (P = .157). Additionally, there was no significant difference in the average pain score between these 2 states (P = .221). The median time for catheter placement in the PVB group was 5 minutes, which was shorter than that (14 minutes) in the TEA group (P < .001). Moreover, the catheter placement failure rate in the PVB group was lower than that in the TEA group (P = .038). The incidence of hypotension (P = .016) and urinary retention (P = .006) in the PVB group was lower than that in the TEA group. CONCLUSIONS: PVB can provide pain relief that is similar to that of TEA but with no additional puncture pain, a shorter catheter placement time, and fewer side effects in patients undergoing video-assisted thoracoscopic surgery.

Clinical efficacy of different open approaches in the surgical treatment of thoracolumbar tuberculosis: a single-center retrospective comparative study.

OBJECTIVE: To assess the clinical efficacy of three different surgical approaches in the treatment of thoracolumbar tuberculosis. METHODS: A total of 138 patients with thoracolumbar tuberculosis treated by open surgery were retrospectively analyzed. The surgical methods were divided into anterior, posterior and anterior-posterior combined. The hospital stays, amount of bleeding, operative time, preoperative, postoperative and last follow-up ESR, CRP, Frankel score, ODI, VAS, correction and loss rate of kyphosis, fusion rate and complications were recorded and analyzed. RESULTS: The average follow-up was 66 months. The average hospital stay, operative time and amount of bleeding of the anterior-posterior combined group were higher than other groups (P < 0.05). ESR and CRP of all patients were reduced postoperatively (P < 0.05). No significant difference among the three groups was found in the postoperative correction angle of kyphosis (P < 0.05), while the pre- and postoperative Cobb angle as well as correction rate had significant differences. The posterior approach could achieve better correction, and the loss of correction was more in the anterior group, 40.9 percent of patients performed correction loss. The Frankel score, VAS and ODI were significantly reduced among the three groups, and the incidence rate of complications of the anterior approach was lower than the other groups, with a significant difference (P < 0.05). CONCLUSION: The anterior approach has more advantages and fewer complications, which is supposed to give preference to and could not be replaced by the posterior and anterior-posterior combined approach.

Ellagic acid inhibits CDK12 to increase osteoblast differentiation and alleviate osteoporosis in hindlimb-unloaded and ovariectomized mice.

BACKGROUND: Osteoporosis is a highly prevalent bone disease occurred commonly in astronauts and postmenopausal women due to mechanical unloading and estrogen deficiency, respectively. At present, there are some traditional Chinese medicine compounds for preventing and treating osteoporosis induced by simulated microgravity, but the detailed components of the traditional Chinese medicines still need to be confirmed and osteoporosis is still untreatable due to a lack of effective small-molecule natural medicine. PURPOSE: To explore the role of cyclin-dependent kinase 12 (CDK12) in osteoporosis induced by simulated microgravity and the therapeutic effect of CDK12-targeted Ellagic Acid (EA) on osteoporosis. METHODS: Our previous study has suggested that CDK12 as a potential target for treating and preventing osteoporosis. In this study, the role of CDK12 in osteoblasts and mice bone tissues was further studied under simulated microgravity. And by targeting CDK12, natural small-molecule product EA was screened out based on a large scale through the weighted set similarity (WES) method and the therapeutic effects of EA on osteoporosis was investigated in hindlimb-unloaded (HU) mouse model and ovariectomized (OVX) model. RESULTS: The results demonstrated that simulated microgravity inhibited bone formation and up-regulated the expression of CDK12. Furthermore, CDK12-siRNA or THZ531 (an inhibitor of CDK 12) promoted osteoblast differentiation, while the overexpression of CDK12 inhibited osteoblasts differentiation. And we further proved that CDK12-targeted EA showed a rescue effect on osteoblast differentiation inhibition caused by simulated microgravity. EA (50 mg·kg-1·day-1) daily intragastric administration alleviated the symptoms of osteoporosis and accompanied with the improvement of trabecular bone and cortical bone parameters with significantly overexpression of CDK12. CONCLUSION: EA efficiently improves osteoporosis by targeting CDK12, which is a suppresser of osteoblast differentiation and a novel therapeutic target for treating osteoporosis.

Prognosis and conditional nomogram of cervical spine fracture in patients with severe spinal cord injury: a multicenter retrospective study.

INTRODUCTION: Cervical spine fractures with severe spinal cord injury (SCI) are common following cervical spine trauma and are associated with a high mortality rate. Understanding the mortality patterns of patients with cervical spine fractures and severe SCI can offer valuable evidence to surgeons and family members who are required to make critical healthcare decisions. The authors aimed to evaluate the instantaneous death risk and conditional survival (CS) of such patients and developed conditional nomograms to account for different periods of survivors and predict the survival rates. METHODS: Their instantaneous death risks were calculated using the hazard function, and the Kaplan-Meier method was used to evaluate the survival rates. Cox regression was used to choose the variables for the construction of the nomograms. The area under the receiver operating characteristic curve and calibration plots were used to validate the performance of the nomograms. RESULTS: The authors finally included 450 patients with cervical spine fractures and severe SCI using propensity score matching. The instantaneous death risk was the highest during the first 12 months after injury. Surgical treatment can help decrease the instantaneous death risk quickly, especially in early-term surgery. The 5-year CS increased constantly from 73.3% at baseline to 88.0% after 2 years of survival. Conditional nomograms were constructed at baseline and in those who survived for 6 and 12 months. The area under the receiver operating characteristic curve and calibration curves indicated that the nomograms had a good performance. CONCLUSION: Their results improve our understanding of the instantaneous death risk of patients in different periods following injury. CS demonstrated the exact survival rate among medium-term and long-term survivors. Conditional nomograms are suitable for different survival periods in predicting the probability of survival. Conditional nomograms help in understanding the prognosis and improve the shared decision-making approaches.

Effects of material nano-topography on the angiogenesis of type H vessels: Size dependence, cell heterogeneity and intercellular communication.

Type H vessel, a vascular subtype in bone, is a critical regulator of osteogenesis, but how material properties affect this organ-specific vessel remains unknown. Here, titania nanotubes were fabricated on bone implant surface to investigate the effects of nano-topography on type H vessels. In vivo, surface nanotubes with 20-100 nm diameters promoted the angiogenesis of type H vessels and bone regeneration in mouse femurs to different extents, with the best effects induced by 70 nm diameter. In vitro, bone-specific endothelial cells (BECs) and artery endothelial cells (AECs) presented significantly different behaviors on the same material. Nanotubes with 20 nm small diameters significantly improved the adhesion, proliferation, type H differentiation of BECs and their paracrine function to regulate pre-osteoblasts (POBs), possibly via binding integrin ß1 on the cell membrane, but these effects weakened when tube diameter increased, which conflicted with the results in vivo. Further study suggested that the better in vivo effects by larger diameters of 70-100 nm might be exerted indirectly through remodeling the regulation from POBs to BECs, highlighting the underappreciated indirect bio-effects of materials via intercellular communication. These suggest that nanoscale material topography makes significant impact on the angiogenesis of type H vessels, directly via binding integrins on the cell membrane of BECs and indirectly via modulating the regulation from osteoblastic cells to BECs, both in a size-dependent manner. Cells of the same type but from different tissues may show different responses to the same material, thus material properties should be tailored to the specific cell population. In research on material-tissue interactions, conclusions from in vitro experiments exposing a single type of cell to material might deviate from the truth in vivo, because materials may indirectly influence the targeted cells through modulating intercellular communication. These provide new insights into material-tissue interactions.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

Bioactive graphene oxide-functionalized self-expandable hydrophilic and osteogenic nanocomposite for orthopaedic applications.

Polymethyl methacrylate (PMMA) bone cement (PBC) is commonly used in orthopaedic surgery. However, polymerization volumetric shrinkage, exothermic injury, and low bioactivity prevent PBC from being an ideal material. The developed expandable P(MMA-AA-St) well overcomes the volumetric shrinkage of PBC. However, its biomechanical properties are unsatisfactory. Herein, graphene oxide (GO), a hydrophilic material with favourable biomechanics and osteogenic capability, was added to P(MMA-AA-St) to optimize its biomechanics and bioactivity. The GO-modified self-expandable P(MMA-AA-St)-GO nanocomposite (PGBCs) exhibited outstanding compressive strength (>70 â€‹MPa), water absorption, and volume expansion, as well as a longer handling time and a reduced setting temperature. The cytocompatibility of PGBCs was superior to that of PBC, as demonstrated by CCK-8 assay, live-dead cell staining, and flow cytometry. In addition, better osteoblast attachment was observed, which could be attributed to the effects of GO. The improved level of osteogenic gene and protein expression further illustrated the improved cell-material interactions between osteoblasts and PGBCs. The results of an in vivo study performed by filling bone defects in the femoral condyles of rabbits with PGBCs demonstrated promising intraoperative handling properties and convenient implantation. Blood testing and histological staining demonstrated satisfactory in vivo biosafety. Furthermore, bone morphological and microarchitecture analyses using bone tissue staining and micro-CT scanning revealed better bone-PGBCs contact and osteogenic capability. The results of this study indicate that GO modification improved the physiochemical properties, cytocompatibility, and osteogenic capability of P(MMA-AA-St) and overcame the drawbacks of PBC, allowing its material derivatives to serve as effective implantable biomaterials.

Effects of Chemical Composition on the Shape Memory Property of Poly(dl-lactide-co-trimethylene carbonate) as Self-Morphing Small-Diameter Vascular Scaffolds.

Smart materials have great potential in many biomedical applications, in which biodegradable shape memory polymers (SMPs) can be used as surgical sutures, implants, and stents. Poly(dl-lactide-co-trimethylene carbonate) (PDLLTC) represents one of the promising SMPs and is widely used in biomedical applications. However, the relationship between its shape memory property and chemical structure has not been fully studied and needs further elaboration. In this work, PDLLTC copolymers in different compositions have been synthesized, and their shape memory properties have been investigated. It has been found that the shape memory property is related to the chemical composition and polymeric chain segments. The copolymer with a DLLA/TMC ratio of 75:25 (PDLLTC7525) has been demonstrated with great shape fixation and recovery ratio at human body temperature. Furthermore, PDLLTC7525-based self-morphing small-diameter vascular scaffolds adhered with inner electrospun aligned gelatin/hyaluronic acid (Gel/HA) nanofibers have been constructed, as a merit of its shape memory property. The scaffolds have been demonstrated to facilitate the proliferation and adhesion of endothelial cells on the inner layer. Therefore, PDLLTC with tailorable shape memory properties represents a promising candidate for the development of SMPs, as well as for small-diameter vascular scaffolds construction.

Black phosphorous-based biomaterials for bone defect regeneration: a systematic review and meta-analysis.

Critical-sized bone defects are always difficult to treat, and they are associated with a significant burden of disease in clinical practice. In recent decades, due to the fast development of biomaterials and tissue engineering, many bioinspired materials have been developed to treat large bone defects. Due to the excellent osteoblastic ability of black phosphorous (BP), many BP-based biomaterials have been developed to treat bone defects. Therefore, there are abundant studies as well as a tremendous amount of research data. It is urgent to conduct evidence-based research to translate these research data and results into validated scientific evidence. Therefore, in our present study, a qualitative systematic review and a quantitative meta-analysis were performed. Eighteen studies were included in a systematic review, while twelve studies were included in the meta-analysis. Our results showed that the overall quality of experimental methods and reports of biomaterials studies was still low, which needs to be improved in future studies. Besides, we also proved the excellent osteoblastic ability of BP-based biomaterials. But we did not find a significant effect of near-infrared (NIR) laser in BP-based biomaterials for treating bone defects. However, the quality of the evidence presented by included studies was very low. Therefore, to accelerate the clinical translation of BP-based biomaterials, it is urgent to improve the quality of the study method and reporting in future animal studies. More evidence-based studies should be conducted to enhance the quality and clinical translation of BP-based biomaterials.

Instantaneous death risk, conditional survival and optimal surgery timing in cervical fracture patients with ankylosing spondylitis: A national multicentre retrospective study.

Background: The mortality rate in patients with ankylosing spondylitis (AS) and cervical fracture is relatively high. Objectives: This study aimed to investigate the instantaneous death risk and conditional survival (CS) in patients with AS and cervical fracture. We also studied the relationship between surgical timing and the incidence of complications. Methods: This national multicentre retrospective study included 459 patients with AS and cervical fractures between 2003 and 2019. The hazard function was used to determine the risk of instantaneous death. The five-year CS was calculated to show the dynamic changes in prognosis. Results: The instantaneous death risk was relatively high in the first 6 months and gradually decreased over time in patients with AS and cervical fracture. For patients who did not undergo surgery, the instantaneous risk of death was relatively high in the first 15 months and gradually decreased over time. For patients with American Spinal Injury Association impairment scale (ASIA) A and B, the 5-year CS was 55.3% at baseline, and improved steadily to 88.4% at 2 years. Odds ratios (ORs) for pneumonia, electrolyte disturbance, respiratory insufficiency, and phlebothrombosis decreased as the surgery timing increased. Conclusion: Deaths occurred mainly in the first 6 months after injury and gradually decreased over time. Our study highlights the need for continued surveillance and care in patients with AS with cervical fractures and provides useful survival estimates for both surgeons and patients. We also observed that early surgery can significantly increase functional recovery, and decrease the incidence of complications and rehospitalisation.

Closing-opening wedge osteotomy for the treatment of congenital kyphosis in children.

BACKGROUND: To evaluate the safety and effectiveness of posterior closed-open wedge osteotomy for treatment of congenital kyphosis in children. METHODS: Imaging and clinical data from January 2010 to December 2019 of posterior closed-open wedge osteotomy of congenital kyphosis with at least 2-year follow up was analyzed retrospectively. Perioperative indicators such as operation time, osteotomy site, osteotomy method and occurrence of complications, and imaging indicators were observed. The 3D printed models were used to measure the expanded distance of anterior edge vertebra and closed length of spinal canal line. The clinical effect was evaluated through SRS-22 questionnaires. RESULTS: There were 15 CK patients in this study. The osteotomy segments and details are as follows: 1 case each for T6-9 and L2, 2 cases at T11, 3 cases at T12, and 6 cases at L1. The average operation time was 314 min, the average blood loss was 970 mL, the average fusion range was 6.3 segments, and the average time of follow up was 70.5 months. The Cobb angle of local kyphosis was corrected from 65.6 ± 18.8° to 11.3 ± 7.1°(p < .001). The range of kyphosis correction was 40-90°, and average correction rate was 83.2% (67.7-95.7%). The correction was stable in follow-up, and the kyphotic angle was 11.0 ± 7.6 (p = .68). The preoperative SVA was 31.5 ± 21.8 mm, and the postoperative recovery was 18.0 ± 15.5, while the last follow-up was 9.1 ± 7.9. The p values were 0.02 and 0.07 respectively. By using 3D printed models, the expanded distance of anterior edge vertebra and closed length of spinal canal line were 14.5 ± 7.5 mm and 24.5 ± 8.0 mm respectively. Self-image and satisfaction in SRS-22 improved significantly. There was no recurrence of deformity and junctional kyphosis. CONCLUSIONS: The posterior closing-opening wedge osteotom for treatment of congenital kyphosis in children is satisfactory, if selected appropriately. During the longitudinal follow-up, the patients could achieve solid fusion and the correction could be well maintained.Evidence of Confidence: IVa.

LOX and Its Methylation Impact Prognosis of Diseases and Correlate with TAM Infiltration in ESCA.

Background: ESCA is one of the digestive tract tumors with a high fatality. It is implicated in an intricate gene regulation process, but the pathogenesis remains ambiguous. Methods: The study used the packages of Limma from R software to analyze DEGs of ESCA in the GEO database and TCGA database. We employed the DAVID website for enrichment analysis, and the string database constructed the PPI network. Hub genes were identified from ESCA DEGs with Cytoscape MCODE. We evaluated the clinical relevance of LOX expression and its DNA methylation in the cBioPortal database and explored the roles of LOX in ESCA immunity, especially immune cell infiltration levels and immune checkpoint expression, by immunedeconv package of R software. Conclusions: The overexpression of LOX in ESCA is regulated by DNA hypomethylation; LOX overexpression or LOX hypomethylation can predict a worse prognosis in patients with ESCA. Besides, LOX may be involved in TIME regulation, promoting the infiltration levels and function of TAM. Hence, high LOX expression affected by DNA hypomethylation has an essential role in patients with ESCA, which may become an effective prognostic marker and therapeutic target.