T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Biomechanical response of lumbar intervertebral disc in daily sitting postures: a poroelastic finite element analysis.

This study aims to establish and validate a poroelastic L4-L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.

Dynamic changes in mechanical properties of the adult rat spinal cord after injury.

Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.

The origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after spinal cord injury.

Accaumulating studies focus on the effects of C3-positive A1-like phenotypes and S100A10-positive A2-like phenotypes of reactive astrocytes on spinal cord injury (SCI), however the origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after SCI remain poorly understood. Through transgenic mice and lineage tracing, we aimed to determine the origins of C3- and S100A10-positive reactive astrocytes. Meanwhile, the distribution and dynamic changes in C3- and S100A10-positive reactive astrocytes were also detected in juvenile and adult SCI mice models and cultured astrocytes. Combing with bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq) and bioinformatic analysis, we further explored the dynamic transcripts changes of C3- and S100A10-positive reactive astrocytes after SCI. We confirmed that resident astrocytes produced both C3- and S100A10-positive reactive astrocytes, whereas ependymal cells regenerated only S100A10-positive reactive astrocytes in lesion area. Importantly, C3-positive reactive astrocytes were predominantly activated in adult SCI mice, while S100A10-positive reactive astrocytes were hyperactivated in juvenile mice. Furthermore, we observed that C3- and S100A10-positive reactive astrocytes had a dynamic transformation process at different time in vitro and vivo, and a majority of intermediate states of C3- and S100A10-positive reactive astrocytes were found during transformation. RNA-seq and scRNA-seq results further confirmed that the transcripts of C3-positive reactive astrocytes and their lipid toxicity were gradually increased with time and age. In contrast, S100A10-positive reactive astrocytes transcripts increased at early time and then gradually decreased after SCI. Our results provide insight into the origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after SCI, which would be valuable resources to further target C3- and S100A10-positive reactive astrocytes after SCI.

Effect of degenerative factors on cervical spinal cord during flexion and extension: a dynamic finite element analysis.

Spinal cord injury (SCI) is a global problem that brings a heavy burden to both patients and society. Recent investigations indicated degenerative disease is taking an increasing part in SCI with the growth of the aging population. However, little insight has been gained about the effect of cervical degenerative disease on the spinal cord during dynamic activities. In this work, a dynamic fluid-structure interaction model was developed and validated to investigate the effect of anterior and posterior encroachment caused by degenerative disease on the spinal cord during normal extension and flexion. Maximum von-Mises stress and maximum principal strain were observed at the end of extension and flexion. The abnormal stress distribution caused by degenerative factors was concentrated in the descending tracts of the spinal cord. Our finding indicates that the excessive motion of the cervical spine could potentially exacerbate spinal cord injury and enlarge injury areas. Stress and strain remained low compared to extension during moderate flexion. This suggests that patients with cervical degenerative disease should avoid frequent or excessive flexion and extension which could result in motor function impairment, whereas moderate flexion is safe. Besides, encroachment caused by degenerative factors that are not significant in static imaging could also cause cord compression during normal activities.

Effect of Velocity and Contact Stress Area on the Dynamic Behavior of the Spinal Cord Under Different Testing Conditions.

Knowledge of the dynamic behavior of the spinal cord under different testing conditions is critical for our understanding of biomechanical mechanisms of spinal cord injury. Although velocity and contact stress area are known to affect external mechanical stress or energy upon sudden traumatic injury, quantitative investigation of the two clinically relevant biomechanical variables is limited. Here, freshly excised rat spinal-cord-pia-arachnoid constructs were tested through indentation using indenters of different sizes (radii: 0.25, 0.50, and 1.00 mm) at various loading rates ranging from 0.04 to 0.20 mm/s. This analysis found that the ex vivo specimen displayed significant nonlinear viscoelasticity at <10% of specimen thickness depth magnitudes. At higher velocity and larger contact stress area, the cord withstood a higher peak load and exhibited more sensitive mechanical relaxation responses (i.e., increasing amplitude and speed of the drop in peak load). Additionally, the cord became stiffer (i.e., increasing elastic modulus) and softer (i.e., decreasing elastic modulus) at a higher velocity and larger contact stress area, respectively. These findings will improve our understanding of the real-time complex biomechanics involved in traumatic spinal cord injury.

Effects of cortical intermittent theta burst stimulation combined with precise root stimulation on motor function after spinal cord injury: a case series study.

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury. We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral (right only) cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots, five times a week. Bilateral resting motor evoked potential amplitude was increased, central motor conduction time on the side receiving cortical stimulation was significantly decreased, and lower extremity motor score, Berg balance score, spinal cord independence measure-III score, and 10 m-walking speed were all increased after treatment. Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment. These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.

The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis.

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BK Ca ) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BK Ca channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BK Ca currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BK Ca channels, resulting in the TN.

The biomechanical effect of preexisting different types of disc herniation in cervical hyperextension injury.

OBJECTIVE: Preexisting severe cervical spinal cord compression is a significant risk factor in cervical hyperextension injury, and the neurological function may deteriorate after a slight force to the forehead. There are few biomechanical studies regarding the influence of pathological factors in hyperextension loading condition. The aim of this study is to analyze the effects of preexisting different types of cervical disc herniation and different degrees of compression on the spinal cord in cervical hyperextension. METHOD: A 3D finite element (FE) model of cervical spinal cord was modeled. Local type with median herniation, local type with lateral herniation, diffuse type with median herniation, and diffuse type with lateral herniation were simulated in neutral and extention positions. The compressions which were equivalent to 10%, 20%, 30%, and 40% of the sagittal diameter of the spinal cord were modeled. RESULTS: The results of normal FE model were consistent with those of previous studies. The maximum von Mises stresses appeared in the pia mater for all 32 loading conditions. The maximum von Mises stresses in extension position were much higher than in neutral position. In most cases, the maximum von Mises stresses in diffuse type were higher than in local type. CONCLUSION: Cervical spinal cord with preexisting disc herniation is more likely to be compressed in hyperextension situation than in neutral position. Diffuse type with median herniation may cause more severe compression with higher von Mises stresses concentrated at the anterior horn and the peripheral white matter, resulting in acute central cord syndrome from biomechanical point of view.

Effects of a contusion load on spinal cord with different curvatures.

The cervical spine injury is a complicated procedure in the combination of different injury loads and postures. The aim of this study is to investigate the injury mechanism considering different types of cervical curvatures subjected to contusion loads. A finite element model of a cervical spinal cord was constructed. Gray matter, white matter and pia matter were modeled and hyperelastic material properties were assigned. Convergence analysis and validation analysis were carried out. The model was simulated in 3 different spinal curvatures and loaded by 2 directions with 4 compression degrees. The maximum von Mises stress in the whole model was concentrated in the pia matter in all loading cases. When investigating spinal cord injury, the pia matter must be considered. For all three curvatures, the stress in the gray matter and white matter was higher in front-to-back loading condition than that in back-to-front loading condition. The front-to-back impact may cause a larger damage. A back-to-front load damaged the structure around the central canal and a front-to-back contusion load damaged the anterior horn of the spinal cord at most time. From the view of the maximum stress, the lordotic curvature did not show significant buffering effect. However, the pathological curvature had large areas affected and the lordotic curvature showed some benefits to some degree from the view of stress distribution.

Sex-specific associations of prenatal exposure to bisphenol A and its alternatives with fetal growth parameters and gestational age.

BACKGROUND: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. OBJECTIVE: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. METHODS: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose-response associations between exposures and outcomes. RESULTS: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: -0.44, -0.15 and -0.21 cm, 95% CI: -0.36, -0.07 comparing the extreme exposure groups, respectively, both p for trends < 0.01). These associations were more pronounced in girls with inverted U-shaped dose-response relationships. Maternal urinary BPA and BPF were positively related to ponderal index (0.05 g/cm3 × 100, 95% CI: 0.01, 0.09 and 0.04 g/cm3 × 100, 95% CI: 0.01, 0.08 comparing the extreme exposure groups, respectively, both p for trends = 0.02), and maternal urinary BPS was associated with shorter gestational age (-0.20 weeks, 95% CI: -0.37, -0.03 comparing the extreme exposure groups, p for trend = 0.02). These associations were only observed in girls and exhibited a linear dose-response relationship. CONCLUSIONS: Prenatal BPA, BPF, and BPS exposures were associated with detrimental effects on fetal growth parameters, and stronger effects were noted in female infants.

Fixation of distal radius fracture with volar locking palmar plates while preserving pronator quadratus through the minimally invasive approach.

BACKGROUND: The volar locking plate technique with an L-shaped incision of the PQ muscle through the classic volar Henry approach is a popular method for treating distal radius fractures. Recently we revised and improved this traditional technique by performing mini-invasive surgery. OBJECTIVE: The purpose of this study was to evaluate the clinical effects after fixation of distal radius fracture with volar locking palmar plates while preserving the pronator quadratus through minimally invasive approach. METHODS: From May 2014 to March 2017, 58 patients (38 males and 21 females) with an age range of 22-72 years (mean age 44.6 years) and with distal radius fractures underwent open reduction and internal fixation with volar locking palmar plates. The patients were classified as 23A-2 through 23C-2 according to the Orthopedic Trauma Association fracture classification system. All surgeries were completed by one trained team. The group that received volar locking palmar plates of distal radius performed with the traditional method through Henry approach involved 33 patients (21 males and 12 females) and the group that received PQ through minimally invasive approach group involved 25 patients (16 males and 9 females). We compared the two groups for wrist pain, forearm range of motion, grip strength, preoperative complications and wrist functional recovery score. RESULTS: The minimum follow-up for the whole cohort was one year. The differences between the two groups were significant in terms of wrist pain, forearm range of motion, grip strength and wrist function at 1, 2, 6 weeks postoperatively, but insignificant at 3 and 12 months postoperatively. In the minimally invasive group a case of limited extension of the forefinger 3 months postoperatively was found. No significant differences were found for preoperative complications and radiographs postoperatively. CONCLUSION: Fixation with volar locking palmar plates through minimally invasive approach is a satisfactory and optional method in the treatment of distal radius fractures. This technique yields better early wrist function, shortens rehabilitation time and gets high psychological satisfaction.

Solid lipid nanoparticles loading with curcumin and dexanabinol to treat major depressive disorder.

Dexanabinol (HU-211) is an artificially synthesized cannabinoid derivative that exerts neuroprotective effects through anti-inflammatory and antioxidant effects. Curcumin exhibits antidepressant effects in the treatment of major depressive disorder. To investigate the antidepressant effects of solid lipid nanoparticles loaded with both curcumin and dexanabinol, and the underlying mechanisms associated with this combination, we established wild-type (CBR1+/+) and cannabinoid receptor 1 (CBR1) knockout (CBR1-/-) mouse models of major depressive disorder, through the intraperitoneal injection of corticosterone, for 3 successive days, followed by treatment with intraperitoneal injections of solid lipid nanoparticles loading with curcumin (20 mg/kg) and dexanabinol (0.85 mg/kg), for 2 successive days. Our results revealed that solid lipid nanoparticle loading with curcumin and dexanabinol increased the mRNA and protein expression levels of the mature neuronal markers neuronal nuclei, mitogen-activated protein 2, and neuron-specific beta-tubulin III, promoted the release of dopamine and norepinephrine, and increased the mRNA expression of CBR1 and the downstream genes Rasgef1c and Egr1, and simultaneously improved rat locomotor function. However, solid lipid nanoparticles loaded with curcumin and dexanabinol had no antidepressant effects on the CBR1-/- mouse models of major depressive disorder. This study was approved by the Institutional Ethics Committee of Tongji Hospital of Tongji University, China (approval No. 2017-DW-020) on May 24, 2017.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury.

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.

Kindergartens Reopening in the Period of Regular Epidemic Prevention and Control, Benefitial or Harmful?

In the period of regular epidemic prevention and control of Coronavirus disease 2019 (COVID-19) in our country, work resumption has been fully advanced. But there are still new sporadic local cases and imported cases across the country. In this situation, whether kindergartens reopening will increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread still remains uncertain. We reviewed two pediatric patients with moderate COVID-19, collected the epidemiologic information and monitored the cycle threshold value of rectal specimen and the viral loads, and discussed the transmission of SARS-CoV-2 in pediatric patients and the virulence of feces in children with moderate COVID-19, in order to analyze the risk of kindergartens reopening.

Effects of contusion load on cervical spinal cord: A finite element study.

Injury of cervical spine is a common injury of locomotor system usually accompanied by spinal cord injury, however the injury mechanism of contusion load to the spinal cord is not clear. This study aims to investigate its injury mechanism associated with the contusion load, with different extents of spinal cord compression. A finite element model of cervical spinal cord was established and two scenarios of contusion injury loading conditions, i.e. back-to-front and front-to-back loads, were adopted. Four different compression displacements were applied to the middle section of the cervical spinal cord. The distributions of von Mises stress in middle transverse cross section were obtained from the finite element analysis. For the back-to-front loading scenario, the stress concentration was found in the area at and near the central canal and the damage may lead to the central canal syndrome from biomechanical point of view. With the front-to-back load, the maximum von Mises stress located in central canal area of gray matter when subject to 10% compression, whilst it appeared at the anterior horn when the compression increased. For the white matter, the maximum von Mises stress appeared in the area of the anterior funiculus. This leads to complicated symptoms given rise by damage to multiple locations in the cervical spinal cord. The illustrative results demonstrated the need of considering different loading scenarios in understanding the damage mechanisms of the cervical spinal cord, particularly when the loading conditions were given rise by different pathophysiological causes.

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation.

Spinal cord injury is linked to the interruption of neural pathways, which results in irreversible neural dysfunction. Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury, which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies. Besides the involvement of endogenous stem cells in neurogenesis and neural repair, exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases. However, to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury, appropriate interventional measures (e.g., neuromodulation) should be adopted. Neuromodulation techniques, such as noninvasive magnetic stimulation and electrical stimulation, have been safely applied in many neuropsychiatric diseases. There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system; namely, by exciting, inhibiting, or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury. Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth, encourages the formation of new synaptic connections to promote neural plasticity, and improves motor function recovery in patients with spinal cord injury. With the development of biomaterial technology and biomechanical engineering, several emerging treatments have been developed, such as robots, brain-computer interfaces, and nanomaterials. These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury. However, large-scale clinical trials need to be conducted to validate their efficacy. This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence, to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.

A Near-Infrared Peptide Probe with Tumor-Specific Excretion-Retarded Effect for Image-Guided Surgery of Renal Cell Carcinoma.

Image-guided surgery plays a crucial role in realizing complete tumor removal, reducing postoperative recurrence and increasing patient survival. However, imaging of tumor lesion in the typical metabolic organs, e.g., kidney and liver, still has great challenges due to the intrinsic nonspecific accumulation of imaging probes in those organs. Herein, we report an in situ self-assembled near-infrared (NIR) peptide probe with tumor-specific excretion-retarded (TER) effect in tumor lesions, enabling high-performance imaging of human renal cell carcinoma (RCC) and achieving complete tumor removal, ultimately reducing postoperative recurrence. The NIR peptide probe first specifically recognizes αvß3 integrin overexpressed in renal cancer cells, then is cleaved by MMP-2/9, which is up-regulated in the tumor microenvironment. The probe residue spontaneously self-assembles into nanofibers that exhibit an excretion-retarded effect in the kidney, which contributes to a high signal-to-noise (S/N) ratio in orthotopic RCC mice. Intriguingly, the TER effect also enables precisely identifying eye-invisible tiny lesions (<1 mm), which contributes to complete tumor removal and significantly reduces the postoperative recurrence compared with traditional surgery. Finally, the TER strategy is successfully employed in high-performance identification of human RCC in an ex vivo kidney perfusion model. Taken together, this NIR peptide probe based on the TER strategy is a promising method for detecting tumors in metabolic organs in diverse biomedical applications.

A modified technique for tibial bone sparing in unicompartmental knee arthroplasty.

BACKGROUND: Previously, the authors modified the surgical technique to preserve tibial bone mass for Oxford unicompartmental knee arthroplasty (UKA). The purpose of this study was to determine the clinical outcomes and values of this modified technique. METHODS: Clinical data of 34 consecutive patients who underwent the unilateral modified UKA technique (modified group, 34 knees) were retrospectively analyzed. To compare the outcome, a match-paired control group (conventional group, 34 knees) of an equal number of patients using the conventional technique system in the same period were selected and matched with respect to diagnosis, age, pre-operative range of motion (ROM), and radiological grade of knee arthrosis. Clinical outcomes including knee Hospital for Special Surgery (HSS) score, ROM, and complications were compared between the two groups. Post-operative radiographic assessments included hip-knee-ankle angle (HKA), joint line change, implant position, and alignment. RESULTS: The mean follow-up time was 38.2 ±â€Š6.3 months. There was no difference in baseline between the two groups. The amount of proximal tibial bone cut in the modified group was significantly less than that of the conventional group (4.7 ±â€Š1.1 mm vs. 6.7 ±â€Š1.3 mm, t = 6.45, P < 0.001). Joint line was elevated by 2.1 ±â€Š1.0 mm in the modified group compared with -0.5 ±â€Š1.7 mm in the conventional group (t = -7.46, P < 0.001). No significant differences were observed between the two groups after UKA with respect to HSS score, VAS score, ROM, and HKA. Additionally, the accuracy of the post-operative implant position and alignment was similar in both groups. As for implant size, the tibial implant size in the modified group was larger than that in the conventional group (χ = 4.95, P = 0.035). CONCLUSIONS: The modified technique for tibial bone sparing was comparable with the conventional technique in terms of clinical outcomes and radiographic assessments. It can preserve tibial bone mass and achieve a larger cement surface on the tibial side.