Spinal cord injury in high-risk complex adult spinal deformity surgery: review of incidence and outcomes from the Scoli-RISK-1 study.

STUDY DESIGN: Clinical case series. OBJECTIVE: To describe the cause, treatment and outcome of 6 cases of perioperative spinal cord injury (SCI) in high-risk adult deformity surgery. SETTING: Adult spinal deformity patients were enrolled in the multi-center Scoli-RISK-1 cohort study. METHODS: A total of 272 patients who underwent complex adult deformity surgery were enrolled in the prospective, multi-center Scoli-RISK-1 cohort study. Clinical follow up data were available up to a maximum of 2 years after index surgery. Cases of perioperative SCI were identified and an extensive case review was performed. RESULTS: Six individuals with SCI were identified from the Scoli-RISK-1 database (2.2%). Two cases occurred intraoperatively and four cases occurred postoperatively. The first case was an incomplete SCI due to a direct intraoperative insult and was treated postoperatively with Riluzole. The second SCI case was caused by a compression injury due to overcorrection of the deformity. Three cases of incomplete SCI occurred; one case of postoperative hematoma, one case of proximal junctional kyphosis (PJK) and one case of adjacent segment disc herniation. All cases of post-operative incomplete SCI were managed with revision decompression and resulted in excellent clinical recovery. One case of incomplete SCI resulted from infection and PJK. The patient's treatment was complicated by a delay in revision and the patient suffered persistent neurological deficits up to six weeks following the onset of SCI. CONCLUSION: Despite the low incidence in high-risk adult deformity surgeries, perioperative SCI can result in devastating consequences. Thus, appropriate postoperative care, follow up and timely management of SCI are essential.

CD31 orchestrates metabolic regulation in autophagy pathways of rheumatoid arthritis.

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

Increased lengthening frequency does not adversely affect the EOSQ scores in magnetically controlled growing rod surgeries in 133 subjects followed to final fusion.

PURPOSE: Magnetically Controlled Growing Rod (MCGR) allows frequent outpatient rod lengthening when treating Early Onset Scoliosis (EOS) patients. But there is lack of expert consensus on the optimal MCGR lengthening interval. EOS 24-Item Questionnaire (EOSQ) is validated for assessing health-related quality of life (HrQOL), family burden, and satisfaction. This is the first study assessing how MCGR lengthening intervals affects patient-perceived outcomes. METHODS: This is a multicentred cohort study with subjects recruited from 2012 to 2018 and followed till fusion. EOS subjects who underwent MCGR surgeries were grouped into high, medium or low lengthening interval subgroups based on 16 and 20 week cut-offs. Repeated measure analysis was performed on EOSQ's specified 12 domains. EOSQ results were taken: before index surgery, after index surgery, and prior to definitive treatment. Demographic, clinical and radiographic data were included in model adjustment. RESULTS: 133 subjects with mean follow-up of 3.5 (± 1.3) years were included, with 60 males and 73 females; 45 idiopathic, 23 congenital, 38 neuromuscular, and 27 syndromic patients. Mean Cobb angle at surgery was 67° (± 22°) with mean age of 8.3 (± 2.5) years. Between groups, clinical and radiographic parameters were comparable. Higher EOSQ scores in medium lengthening interval subgroup was present in fatigue (p = 0.019), emotion (p = 0.001), and parental impact (p = 0.049) domains, and overall score (p = 0.046). Trendline contrast between subgroups were present in general health (p = 0.006) and physical function (p = 0.025) domains. CONCLUSION: Patient-perceived outcome improvements appear similar between lengthening interval subgroups. All MCGR lengthening intervals were tolerated by patients and family, with no negative impact observed. LEVEL OF EVIDENCE: Prognostic Level III.

Opioid Use Prior to Adult Spine Deformity Correction Surgery is Associated With Worse Pre- and Postoperative Back Pain and Prolonged Opioid Demands.

STUDY DESIGN: Prospective multicenter database post-hoc analysis. OBJECTIVES: Opioids are frequently prescribed for painful spinal conditions to provide pain relief and to allow for functional improvement, both before and after spine surgery. Amidst a current opioid epidemic, it is important for providers to understand the impact of opioid use and its relationship with patient-reported outcomes. The purpose of this study was to evaluate pre-/postoperative opioid consumption surrounding ASD and assess patient-reported pain outcomes in older patients undergoing surgery for spinal deformity. METHODS: Patients ≥60 years of age from 12 international centers undergoing spinal fusion of at least 5 levels and a minimum 2-year follow-up were included. Patient-reported outcome scores were collected using the Numeric Rating Scale for back and leg pain (NRS-B; NRS-L) at baseline and at 2 years following surgery. Opioid use, defined based on a specific question on case report forms and question 11 from the SRS-22r questionnaire, was assessed at baseline and at 2-year follow-up. RESULT: Of the 219 patients who met inclusion criteria, 179 (81.7%) had 2-year data on opioid use. The percentages of patients reporting opioid use at baseline (n = 75, 34.2%) and 2 years after surgery (n = 55, 30.7%) were similar (P = .23). However, at last follow-up 39% of baseline opioid users (Opi) were no longer taking opioids, while 14% of initial non-users (No-Opi) reported opioid use. Regional pre- and postoperative opioid use was 5.8% and 7.7% in the Asian population, 58.3% and 53.1% in the European, and 50.5% and 40.2% in North American patients, respectively. Baseline opioid users reported more preoperative back pain than the No-Opi group (7.0 vs 5.7, P = .001), while NRS-Leg pain scores were comparable (4.8 vs 4, P = .159). Similarly, at last follow-up, patients in the Opi group had greater NRS-B scores than Non-Opi patients (3.2 vs 2.3, P = .012), but no differences in NRS-Leg pain scores (2.2 vs 2.4, P = .632) were observed. CONCLUSIONS: In this study, almost one-third of surgical ASD patients were consuming opioids both pre- and postoperatively world-wide. There were marked international variations, with patients from Asia having a much lower usage rate, suggesting a cultural influence. Despite both opioid users and nonusers benefitting from surgery, preoperative opioid use was strongly associated with significantly more back pain at baseline that persisted at 2-year follow up, as well as persistent postoperative opioid needs.

The Fate of The Broken Tether: How Do Curves Treated with Vertebral Body Tethering Behave After Tether Breakage?

STUDY DESIGN: Retrospective, Multicenter. OBJECTIVE: Assess curve progression and occurrence of revision surgery following tether breakage after vertebral body tethering (VBT). SUMMARY OF BACKGROUND DATA: Tether breakage after VBT is common with rates up to 50% reported. In these cases, it remains unknown whether the curve will progress or remain stable. METHODS: Adolescent and juvenile idiopathic scoliosis patients in a multicenter registry with ≥2 year-follow-up after VBT were reviewed. Broken tethers were listed as postoperative complications and identified by increased screw divergence of >5° on serial radiographs. Revision procedures and curve magnitude at subsequent visits were recorded. RESULTS: Of 186 patients who qualified for inclusion, 84 (45.2%) patients with tether breakage were identified with a mean age at VBT of 12.4±1.4 years and mean curve magnitude at index procedure of 51.8°±8.1°. Tether breakage occurred at a mean of 30.3±11.8 months and mean curve of 33.9°±13.2°. Twelve patients (12/84, 14.5%) underwent 13 revision procedures after VBT breakage, including 6 tether revisions and 7 conversions to fusion. All tether revisions occurred within 5 months of breakage identification. No patients with curves <35° after breakage underwent revision. Revision rate was greatest in skeletally immature (Risser 0-3) patients with curves ≥35° at time of breakage (Risser 0-3: 9/17, 53% vs. Risser 4-5: 3/23, 13%, P=0.01).Curves increased by 3.1° and 3.7° in the first and second year, respectively. By two years, 15/30 (50%) progressed >5° and 8/30 (26.7%) progressed greater than 10°. Overall, 66.7% (40/60) reached a curve magnitude >35° at their latest follow-up, and 14/60 (23.3%) reached a curve magnitude greater than 45°. Skeletal maturity did not affect curve progression after tether breakage (P>0.26), but time to rupture did (P=0.048). CONCLUSION: While skeletal immaturity and curve magnitude were not independently associated with curve progression, skeletally immature patients with curves ≥35° at time of rupture are most likely to undergo additional surgery. Most patients can expect progression at least 5° in the first two years after tether breakage, though longer-term behavior remains unknown. LEVEL OF EVIDENCE: III.

Governing cross-border healthcare in mainland China: a scoping review of national policies from 2002 to 2022.

This study reviews national-level policies regulating cross-border healthcare in mainland China after it acceded to the World Trade Organization (WTO). Policy documents from official websites of the State Council and 19 ministries were screened, from which 487 policy documents were analyzed. WTO's five modes of trade and WHO's six building blocks of healthcare system were used to guide the analysis of policymaking patterns, charting of policy evolution process, identification of key policy areas, differentiation of 29 detailed policy themes, and identification of major countries/regions involved in cross-border healthcare. The findings lead to four policy recommendations: (1) to establish a national-level committee to govern cross-border healthcare, (2) to build an information system to comprehensively integrate various information on cross-border healthcare consumption and provision, (3) to take more proactive policy actions in healthcare internationalization, and (4) to carry out reform experiments in key sub-national regions to fully explore various possibilities in developing and regulating cross-border healthcare.

Elasticity and cross-sectional thickness of paraspinal muscles in progressive adolescent idiopathic scoliosis.

Objectives: (1) Compare the cross-sectional thickness (CST) and shear wave speed (SWS) of paraspinal muscles (PSM) in adolescent idiopathic scoliosis (AIS) with and without curve progression; (2) investigate the relationship between CST/SWS and radiographic characteristics in AIS with curve progression; (3) compare the CST/SWS between AIS and non-scoliosis controls. Methods: This cross-sectional study analyzed the CST and SWS of PSM in 48 AIS with mild to moderate curvature and 24 non-scoliosis participants. Participants with scoliosis greater than 45° of Cobb angles were excluded. The Change of Cobb angles within the last 6-months was retrieved to allocate AIS into progression and non-progression groups. The SWS and CST of multifidus; longissimus and iliocostalis of the major curve were measured using B-mode ultrasound image with an elastography mode. Discrepancies of the SWS (SWS-ratio: SWS on the convex side divided by SWS on the concave side) and CST (CST-ratio: CST on the convex side divided by CST on the concave side) at the upper/lower end and apical vertebrae were studied. Results: A higher SWS at the apical vertebrae on the concave side of the major curve (multifidus: 3.9 ± 1.0 m/s vs. 3.1 ± 0.6 m/s; p < 0.01, longissimus: 3.3 ± 1.0 m/s vs. 3.0 ± 0.9 m/s; p < 0.01, iliocostalis: 2.8 ± 1.0 m/s vs. 2.5 ± 0.8 m/s; p < 0.01) was observed in AIS with curve progression. A lower SWS-ratio at apical vertebrae was detected with a greater vertebral rotation in participants with curve progression (multifidus [grade II]: 0.7 ± 0.1 vs. grade I: 0.9 ± 0.2; p = 0.03, longissimus [grade II]: 0.8 ± 0.2 vs. grade I: 1.1 ± 0.2; p < 0.01). CST was not different among the progressive, non-progressive AIS and non-scoliosis controls. Conclusions: Increased SWS of PSM without change of CST was observed on the concave side of the major curve in participants with progressive AIS.

Ultralight, strong, and self-reprogrammable mechanical metamaterials.

Versatile programmable materials have long been envisioned that can reconfigure themselves to adapt to changing use cases in adaptive infrastructure, space exploration, disaster response, and more. We introduce a robotic structural system as an implementation of programmable matter, with mechanical performance and scale on par with conventional high-performance materials and truss systems. Fiber-reinforced composite truss-like building blocks form strong, stiff, and lightweight lattice structures as mechanical metamaterials. Two types of mobile robots operate over the exterior surface and through the interior of the system, performing transport, placement, and reversible fastening using the intrinsic lattice periodicity for indexing and metrology. Leveraging programmable matter algorithms to achieve scalability in size and complexity, this system design enables robust collective automated assembly and reconfiguration of large structures with simple robots. We describe the system design and experimental results from a 256-unit cell assembly demonstration and lattice mechanical testing, as well as a demonstration of disassembly and reconfiguration. The assembled structural lattice material exhibits ultralight mass density (0.0103 grams per cubic centimeter) with high strength and stiffness for its weight ( 11.38 kilopascals and 1.1129 megapascals, respectively), a material performance realm appropriate for applications like space structures. With simple robots and structure, high mass-specific structural performance, and competitive throughput, this system demonstrates the potential for self-reconfiguring autonomous metamaterials for diverse applications.

Incidence of back pain from initial presentation to 3 years of follow-up in subjects with untreated adolescent idiopathic scoliosis.

BACKGROUND: Although back pain may be present in subjects with adolescent idiopathic scoliosis (AIS), its natural history is unknown. Therefore, this study evaluated the incidence of back pain in scoliotic adolescents longitudinally. METHODS: This retrospective analysis examined prospectively collected pain subscale data of the Scoliosis Research Society questionnaire between the initial presentation and up to 3 years of follow-up. Consecutive subjects with AIS aged 10-18 at baseline managed by observation within the study period were included. Study subjects with at least one time point of follow-up data were considered. Alternatively, a group with physiotherapy-treated was also included for comparison. RESULTS: We enrolled 428 subjects under observation. The incidence of back pain among study subjects was 14.7%, 18.8%, and 19.0% for the first year, second year, and third year of follow-up, respectively. Most experienced mild pain (1 out of 5 points) throughout the study. Neither incidence nor intensity of pain significantly differed between subjects under observation and received physiotherapy. Additionally, study subjects with a new onset of back pain had poorer function, self-image, and mental health scores than those without pain. CONCLUSION: We investigated the incidence of back pain longitudinally in subjects suffering from AIS. Further validation of the current results is warranted.

Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients.

BACKGROUND: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. METHODS: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. RESULTS: In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9-16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°-25°), 40 (13.8%) moderate (25°-50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07-1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4-3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23-40) postoperatively. CONCLUSION: The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

Impact of mental health components on the development of back pain in young adults with adolescent idiopathic scoliosis.

BACKGROUND: Back pain occurs commonly in adults and is multifactorial in nature. This study aimed to assess the prevalence and intensity of back pain during young adulthood in subjects with adolescent idiopathic scoliosis (AIS), as well as factors that may be associated with its prognosis. METHODS: Subjects with AIS aged 20-39 treated conservatively were included in this study. Patient-reported outcome measures in adulthood involved episodes of back pain, and scales of self-image, depression, anxiety, and stress. Additionally, pain, self-image, and mental health scores were retrieved at the first clinic consultation. Occurrence of back pain was defined as a numeric pain rating scale ≥ 6. RESULTS: 101 participants were enrolled. The prevalence of back pain in the lifetime, past 12 months, past 6 months, past 1 month, past 7 days, and past 24 h were 37%, 35%, 31%, 27%, 23%, and 20%, respectively. Male, self-image, and depression were significant associated factors for the development of back pain at all time points. Furthermore, the analyses of the initial presentation of participants have shown that participants with back pain in adulthood were characterised by poor self-image and mental health during their adolescence. CONCLUSION: The present study addressed the natural history of back pain in young adults with conservatively treated AIS. Psychological makeup has been shown to constitute the development of back pain and is strongly hinted as an early sign of having back pain in adulthood among subjects with AIS.

Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis.

Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic peroxisome proliferator-activated receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.

An intelligent composite model incorporating global / regional X-rays and clinical parameters to predict progressive adolescent idiopathic scoliosis curvatures and facilitate population screening.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) affects up to 5% of the population. The efficacy of school-aged screening remains controversial since it is uncertain which curvatures will progress following diagnosis and require treatment. Patient demographics, vertebral morphology, skeletal maturity, and bone quality represent individual risk factors for progression but have yet to be integrated towards accurate prognostication. The objective of this work was to develop composite machine learning-based prediction model to accurately predict AIS curves at-risk of progression. METHODS: 1870 AIS patients with remaining growth potential were identified. Curve progression was defined by a Cobb angle increase in the major curve of ≥6° between first visit and skeletal maturity in curves that exceeded 25°. Separate prediction modules were developed for i) clinical data, ii) global/regional spine X-rays, and iii) hand X-rays. The hand X-ray module performed automated image classification and segmentation tasks towards estimation of skeletal maturity and bone mineral density. A late fusion strategy integrated these domains towards the prediction of progressive curves at first clinic visit. FINDINGS: Composite model performance was assessed on a validation cohort and achieved an accuracy of 83.2% (79.3-83.6%, 95% confidence interval), sensitivity of 80.9% (78.2-81.9%), specificity of 83.6% (78.8-84.1%) and an AUC of 0.84 (0.81-0.85), outperforming single modality prediction models (AUC 0.65-0.78). INTERPRETATION: The composite prediction model achieved a high degree of accuracy. Upon incorporation into school-aged screening programs, patients at-risk of progression may be prioritized to receive urgent specialist attention, more frequent follow-up, and pre-emptive treatment. FUNDING: Funding from The Society for the Relief of Disabled Children was awarded to GKHS.

Mechanical characterization and design of biomaterials for nucleus pulposus replacement and regeneration.

Biomaterials for nucleus pulposus (NP) replacement and regeneration have great potential to restore normal biomechanics in degenerated intervertebral discs following nucleotomy. Mechanical characterizations are essential for assessing the efficacy of biomaterial implants for clinical applications. While traditional compression tests are crucial to quantify various modulus values, relaxation behaviors and fatigue resistance, rheological measurements should also be conducted to investigate the viscoelastic properties, injectability, and overall stability upon deformation. To recapitulate the physiological in vivo environment, the use of spinal models is necessary to evaluate the risk of implant extrusion and the restoration of biomechanics under different loading conditions. When designing devices for NP replacement, injectable materials are ideal to fully fill the nucleus cavity and prevent implant migration. In addition to achieving biocompatibility and desirable mechanical characteristics, biomaterial implants should be optimized to avoid implant extrusion or re-herniation post-operatively. This review discusses the most commonly used testing protocols for assessing mechanical properties of biomaterial implants and serves as reference material for enabling researchers to characterize NP implants through a unified approach whereby newly developed biomaterials may be compared and contrasted to existing devices.

Assessment of reliability and validity of a handheld surface spine scanner for measuring trunk rotation in adolescent idiopathic scoliosis.

PURPOSE: To assess the reliability and validity of a handheld scanner (SpineScan3D) for trunk rotation measurement in adolescent idiopathic scoliosis (AIS) subjects, as compared with Scoliometer. METHODS: This was a cross-sectional study with AIS subjects recruited. Biplanar spine radiographs were performed using an EOS imaging system with coronal Cobb angle (CCA) determined. The angle of trunk rotation (ATR) was measured using Scoliometer. SpineScan3D was employed to assess the axial rotation of subjects' back at forward bending, recorded as surface tilt angle (STA). Intra- and inter-examiner repeats were conducted to evaluate the reliability of SpineScan3D. RESULTS: 97 AIS patients were recruited. Intra- and inter-examiner reliability of STA measures were good to excellent in major thoracic and lumbar curves (p < 0.001). A strong correlation was found between STA and ATR measures in both curve types (p < 0.001) with a standard error of the ATR estimate of between 1 and 2 degrees from linear regression models (R squared: 0.8-0.9, p < 0.001). A similar correlation with CCA was found for STA and ATR measures (r: 0.5-0.6, p < 0.002), which also demonstrated a similar sensitivity (72%-74%) and specificity (62%-77%) for diagnosing moderate to severe curves. CONCLUSION: SpineScan3D is a handheld surface scanner with a potential of wide applications in subjects with AIS. The current study indicated that SpineScan3D is reliable and valid for measuring trunk rotation in AIS subjects, comparable to Scoliometer. Further studies are planned to investigate its measurements in coronal and sagittal planes and the potential of this device as a screening and monitoring tool. TRIAL REGISTRATION NUMBER (DATE OF REGISTRATION): HKUCTR-2288 (06 Dec 2017). LEVEL OF EVIDENCE: Level III.

Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis.

Bile acids (BAs) play a crucial role in nutrient absorption and act as key regulators of lipid and glucose metabolism and immune homeostasis. Through the enterohepatic circulation, BAs are synthesized, metabolized, and reabsorbed, with a portion entering the vascular circulation and distributing systemically. This allows BAs to interact with receptors in all major organs, leading to organ-organ interactions that regulate both local and global metabolic processes, as well as the immune system. This review focuses on the whole-body effects of BA-mediated metabolic and immunological regulation, including in the brain, heart, liver, intestine, eyes, skin, adipose tissue, and muscle. Targeting BA synthesis and receptor signaling is a promising strategy for the development of novel therapies for various diseases throughout the body.

A new osteogenic protein isolated from Dioscorea opposita Thunb accelerates bone defect healing through the mTOR signaling axis.

Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named 'HKUOT-S2' protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.

Application of silver nanoparticles for improving motor recovery after spinal cord injury via reduction of pro-inflammatory M1 macrophages.

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.

A solitary osteolytic lesion with pathological fracture in the cervical spine - a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder. The treatment options vary depending on how many organs are involved and how extensive the disease is. In this report, a case of LCH with isolated 6th cervical vertebra (C6) collapse was presented. This case was treated with anterior corpectomy and instrumented fusion, followed by local radiotherapy (RT), with a good clinical outcome up to postoperative six months. CASE PRESENTATION: This was a 47-year-old female patient with a complaint of neck pain and bilateral shoulder pain for two months before consultation. She was initially treated with analgesics, but the pain was persistent. Further radiological evaluations revealed an osteolytic lesion within the C6 vertebral body with a pathological fracture. Magnetic resonance imaging (MRI) with contrast of the cervical spine revealed diffused hypointense signal changes on the T1-weighted images and hyperintense signal changes on the T2-weighted images in the C6 vertebral body, with significant contrast-enhanced infiltration signals. Furthermore, in positron emission tomography-computed tomography (PET-CT), focal hypermetabolism and abnormal uptake signals were seen only in the C6 vertebral body. The patient underwent an anterior cervical corpectomy with instrumented fusion. The histopathological results confirmed the diagnosis of LCH. The patient reported significant pain relief on postoperative day one. Moreover, she was treated by local RT at postoperative one month. Good clinical outcomes were achieved in the form of no pain and recovery in neck mobility up to postoperative six months. No evidence of recurrence was observed at the final follow-up. CONCLUSIONS: This case report describes a treatment option for a solitary C6 collapse with LCH managed by anterior corpectomy and instrumented fusion, followed by local RT, with a good clinical outcome at postoperative six months. More studies are needed to elucidate whether such a treatment strategy is superior to surgery or RT alone.