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Lu Cao,1,* Qian Chen,1,* Li-Bo Jiang,1,* Xiao-Fan Yin,1,2 Chong Bian,1 Hui-Ren Wang,1 Yi-Qun Ma,1 Xiang-Qian Li,1 Xi-Lei Li,1 Jian Dong1 1Department of Orthopaedic Surgery, Zhongshan Hospital, 2Department of Orthopaedic Surgery, Minhang Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Study design: This is an experimental animal study.Objective: The objective of this study was to compare an anterior cervical discectomy and interbody fusion of a novel polylactide/nano-sized β-tricalcium phosphate (PLA/nβ-TCP) bioabsorbable self-retaining cervical fusion cage (BCFC) with an autologous bone graft and polyetheretherketone (PEEK) cages.Background: Although PLA cervical cages have potential advantages compared with traditional materials, they are not currently routinely used in spine surgery because of undesirable effects such as the lack of osteoconductivity and osteolysis around the implant. This study involved the manufacturing of a bioabsorbable cage from PLA/nβ-TCP that was then used as a device for anterior cervical discectomy and fusion (ACDF) on a goat cervical spine fusion model.Materials and methods: Eighteen goats underwent C3/C4 discectomy and were randomly divided into three groups based on the following methods: Group A (n=6), an autologous bone graft; Group B (n=6), PEEK cage filled with an autologous graft; and Group C (n=6), BCFC filled with an autologous iliac bone. Radiography was performed preoperatively and postoperatively and at 1, 4, 8, and 12 weeks after the operation. Disc space height (DSH) was measured at the same time. After 12 weeks, the fused segments were harvested and evaluated with functional radiographic views, biomechanical testing, and histological analyses.Results: Over a 12-week period, the BCFC and PEEK cage groups exhibited significantly higher DSH values than the bone graft group. Additionally, the BCFC group yielded a significantly lower range of motion in axial rotation than both the autologous bone graft and PEEK cage groups. A histologic evaluation revealed an increased intervertebral bone volume/total volume ratio and better interbody fusion in the BCFC group than in the other groups.Conclusion: The BCFC device exhibited better results than the autologous bone graft and PEEK cages in single-level ACDF models in vivo. This device may be a potential alternative to the current PEEK cages. Keywords: goat, cervical spine cages, bioabsorbable, PLA, β-TCP, self-retaining

The use of membrane-based guided bone regeneration techniques has great potential for single-stage reconstruction of critical-sized bone defects. Here, a multifunctional bone regeneration membrane combining flexible elasticity, electrical stimulation (ES) and osteoinductive activity is developed by in situ doping of MXene 2D nanomaterials with conductive functionality and β-TCP particles into a Poly(lactic acid-carbonate (PDT) composite nano-absorbable membrane (P/T/MXene) via electrostatic spinning technique. The composite membrane has good feasibility due to its temperature sensitivity, elastic memory capacity, coordinated degradation profile and easy preparation process. In vitro experiments showed the P/T/MXene membrane effectively promoted the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under ES and enhanced the angiogenic capacity of endothelial cells, which synergistically promoted bone regeneration through neovascularization. In addition, an in vivo rat model of cranial bone defects further confirmed the bone regeneration efficacy of the P/T/MXene membrane. In conclusion, the developed P/T/MXene membrane can effectively promote bone regeneration through their synergistic multifunctional effects, suggesting the membranes have great potential for guiding tissue regeneration and providing guidance for the biomaterials design., (© 2024 Wiley‐VCH GmbH.)

Objective: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed., Methods: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed., Results: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability., Conclusions: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

It is still a great challenge to achieve high selectivity of ethanol in CO 2 electroreduction reactions (CO 2 RR) because of the similar reduction potentials and lower energy barrier of possible other C 2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5 % at -1.0 V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66 mA cm -2 . By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO 2 -to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO 2 -to-EtOH., (© 2024 Wiley-VCH GmbH.)

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E 2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8 + T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge. In this study, a nuclear-targeted photodynamic nanostrategy is developed to establish positive spatiotemporal communication, further activating dual antitumor immunity, namely innate and adaptative immunity. The mSiO 2 -Ion@Ce6-NLS nanoparticles (NPs) are designed, whose surface is modified by ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS: PKKKRKV), and their pores are loaded with the photosensitizer hydrogen chloride e6 (Ce6). Ion-modified NPs enhance intratumoral enrichment, and NLS-modified NPs exhibit nuclear-targeted characteristics to achieve nuclear-targeted photodynamic therapy (nPDT). mSiO 2 -Ion@Ce6-NLS with nPDT facilitate the release of damaged double-stranded DNA from tumor cells to activate macrophages via stimulator of interferon gene signaling and induce the immunogenic cell death of tumor cells to activate dendritic cells via "eat me" signals, ultimately leading to the recruitment of CD8 + T-cells. This therapy effectively strengthens positive communication to reshape the dual antitumor immune microenvironment, further inducing long-term immune memory, and eventually inhibiting tumor growth and recurrence., (© 2023 Wiley-VCH GmbH.)

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the β-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca 2+ release from the endoplasmic reticulum to activate Ca 2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca 2+ homeostasis., (© 2023 Wiley-VCH GmbH.)

Background: In this study, we aimed to analyze the clinical characteristics and prognosis of children with retinoblastoma (RB) in a single center in China with a large sample collection spanning 17 years., Methods: The clinical data of 2790 children with RB treated in Beijing Tongren Hospital from 2005 to 2021 were collected, and a retrospective analysis was conducted., Results: The median age of the participants was 28.3 months. There were 3624 affected eyes, 12.4% of which were in groups A-C, 67.1% in groups D-E and 16.2% were not specified. The primary symptom observed in most cases was a white pupil, accounting for 66.5%, followed by strabismus (12.8%). The median follow-up time was 59.7 months. The enucleation rate was 71.3% (703/986) in a single left eye and 72.5% (702/968) in a single right eye. The overall survival (OS) rate was 95.8% (2444/2552) because 237 patients dropped out, and 109 died. Kaplan‒Meier survival analysis showed that the median survival time (MST) was 125.92 months [95% confidence interval (CI) = 124.83-127.01]. Cox multivariate survival analysis showed that trilateral RB (P = 0.017), metastasis site (P = 0.001), and combined distant tissue metastasis (P = 0.001) were independent prognostic factors for RB. The OS of 44 cases of familial RB was 93.2% (41/44), with an MST of 80.62 months (95% CI = 67.70-93.54)., Conclusions: The timing of eye protection treatment and enucleation should be comprehensively judged to avoid worsening prognosis due to operation time delay. More importantly, the promotion and popularization of diagnosis and treatment technologies are necessary to further improve RB prognosis., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors. Previous studies proposed that NLRP3 was activated by translocation to the mitochondria. However, a recent authoritative study has challenged this model and proved that the Golgi apparatus might be a prerequisite for the activation of NLRP3. In this study, we first developed a Golgi apparatus-targeted photodynamic strategy to induce the activation of NLRP3 by precisely locating organelles. We found that Golgi apparatus-targeted photodynamic therapy could significantly upregulate NLRP3 expression to promote the subsequent release of intracellular proinflammatory contents such as IL-1β or IL-18, creating an inflammatory storm to enhance innate immunity. Moreover, this acute NLRP3 upregulation also activated its downstream classical caspase-1-dependent pyroptosis to enhance tumor immunogenicity, triggering adaptive immunity. Pyroptosis eventually led to immunogenic cell death, promoted the maturation of dendritic cells, and effectively activated antitumor immunity and long-lived immune memory. Overall, this Golgi apparatus-targeted strategy provided molecular insights into the occurrence of immunogenic pyroptosis and offered a platform to remodel the tumor microenvironment.

Replicating the controlled nanofibrillar architecture of collagenous tissue represents a promising approach in the design of tendon replacements that have tissue-mimicking biomechanics─outstanding mechanical strength and toughness, defect tolerance, and fatigue and fracture resistance. Guided by this principle, a fibrous artificial tendon (FAT) was constructed in the present study using an engineering strategy inspired by the fibrillation of a naturally spun silk protein. This bioinspired FAT featured a highly ordered molecular and nanofibrillar architecture similar to that of soft collagenous tissue, which exhibited the mechanical and fracture characteristics of tendons. Such similarities provided the motivation to investigate FAT for applications in Achilles tendon defect repair. In vitro cellular morphology and expression of tendon-related genes in cell culture and in vivo modeling of tendon injury clearly revealed that the highly oriented nanofibrils in the FAT substantially promoted the expression of tendon-related genes combined with the Achilles tendon structure and function. These results provide confidence about the potential clinical applications of the FAT.

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Papilledema refers to the swelling of the optic disk due to increased intracranial pressure. In clinical practice, papilledema is often confused with optic disc edema. Idiopathic intracranial hypertension (IIH) is a major cause of papilledema and there are still misconceptions about the etiology of IIH, the classification and examination of papilledema, and the treatment of IIH. This article elaborates on the misunderstandings that may exist in the diagnosis and treatment of papilledema, in order to lay a foundation for the standardized diagnosis and treatment of papilledema in China.

Due to the limited self-repairing capacity after peripheral nerve injuries (PNI), artificial nerve conduits are widely applied to facilitate neural regeneration. Exogenous electrical stimulation (ES) that is carried out by the conductive conduit regulates the biological behavior of Schwann cells (SCs). Meanwhile, a longitudinal surface structure counts to guide axonal growth to accelerate the end-to-end connection. Currently, there are no conduits equipped with both electrical conduction and axon-guiding surface structure. Herein, a biodegradable, conductive poly(l-lactide-co-caprolactone)/graphene (PLCL/GN) composite conduit is designed. The conduit with 20.96 ± 1.26 MPa tensile strength has a micropatterned surface of 20 µm groove fabricated by microimprint technology and self-assembled polydopamine (PDA). In vitro evaluation shows that the conduits with ES effectively stimulate the directional cell migration, adhesion, and elongation, and enhance neuronal expression of SCs. The rat sciatic nerve crush model demonstrates that the conductive micropatterned conduit with ES promotes the growth of myelin sheath, faster nerve regeneration, and 20-fold functional recovery in vivo. These discoveries prove that the PLCL(G)/PDA/GN composite conduit is a promising tool for PNI treatment by providing the functional integration of physical guidance, biomimetic biological regulation, and bioelectrical stimulation, which inspires a novel therapeutic approach for nerve regeneration in the future., (© 2023 Wiley-VCH GmbH.)

Circadian rhythm (CR) disruption contributes to tumor initiation and progression, however the pharmacological targeting of circadian regulators reversely inhibits tumor growth. Precisely controlling CR in tumor cells is urgently required to investigate the exact role of CR interruption in tumor therapy. Herein, based on KL001, a small molecule that specifically interacts with the clock gene cryptochrome (CRY) functioning at disruption of CR, we fabricated a hollow MnO 2 nanocapsule carrying KL001 and photosensitizer BODIPY with the modification of alendronate (ALD) on the surface (H-MnSiO/K&B-ALD) for osteosarcoma (OS) targeting. The H-MnSiO/K&B-ALD nanoparticles reduced the CR amplitude in OS cells without affecting cell proliferation. Furthermore, nanoparticles-controlled oxygen consumption by inhibiting mitochondrial respiration via CR disruption, thus partially overcoming the hypoxia limitation for photodynamic therapy (PDT) and significantly promoting PDT efficacy. An orthotopic OS model demonstrated that KL001 significantly enhanced the inhibitory effect of H-MnSiO/K&B-ALD nanoparticles on tumor growth after laser irradiation. CR disruption and oxygen level enhancement induced by H-MnSiO/K&B-ALD nanoparticles under laser irradiation were also confirmed in vivo. This discovery first demonstrated the potential of CR controlling for tumor PDT ablation and provided a promising strategy for overcoming tumor hypoxia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Peripapillary hyper-reflective ovoid mass-like structure (PHOMS) is a newly discovered optical coherence tomography (OCT) sign of optic disc in recent years, which can be presented in a variety of optic nerve diseases. At present, the OCT structural characteristics and pathological manifestations of PHOMS have been initially understood. This paper summarizes the related literature published recently. The relationship and the latest research progress between PHOMS and some optic neuropathy were mainly focused, hoping to further deepen the understanding and facilitate its wider clinical application.

The pyrolysis effect of aviation kerosene is common in the regenerative cooling process of hypersonic aircraft scramjets. To find out the effect of inclination variation on the characteristics of aviation kerosene RP-3 considering thermal cracking in a regenerative cooling rectangular channel, a detailed chemical mechanism of RP-3 pyrolysis is introduced to construct a numerical model. The results indicate that the pyrolytic reaction begins at the junction of the heating wall and the side walls, and the main products of pyrolysis are light olefins and alkanes. The thermal cracking reaction slows down the velocity of the main flow on account of the increased density and increased viscosity resulting from the decrease in RP-3 temperature. With the decrease in inclination, thermal cracking is enhanced and the average heat transfer coefficient is decreased, which leads to an increase in wall temperature., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment-specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca 2+ /CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo . Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Optical coherence tomography angiography (OCTA) is a new vascular imaging technology based on high-resolution optical coherence tomography image analysis. It can scan the moving red blood cells in blood vessels for three-dimensional imaging of human retinal and choroidal vessels. Since the close connection of vascular endothelial cells of the blood-retinal barrier is similar to that of the blood-brain barrier, the role of OCTA in the research of pathogenesis and course monitoring of a variety of central system diseases such as Alzheimer's disease, Parkinson's disease, stroke, migraine, multiple sclerosis and optic neuromyelitis has been widely discussed. This article reviews the application and progress of OCTA in central nervous system diseases.

Narrowing the mechanical and electrical mismatch between tissue and implantable microelectronics is essential for reducing immune responses and modulating physioelectrical signals. Nevertheless, the design of such implantable microelectronics remains a challenge due to the limited availability of suitable materials. Here, the fabrication of an electrically and mechanically biocompatible alginate hydrogel ionotronic fiber (AHIF) is reported, which is constructed by combing ionic chelation-assisted wet-spinning and mechanical training. The synergistic effects of these two processes allow the alginate to form a highly-oriented nanofibril and molecular network, with a hierarchical structure highly similar to that of natural fibers. These favourable structural features endow AHIF with tissue-mimicking mechanical characteristics, such as self-stiffening and soft tissue-like mechanical properties. In addition, tissue-like chemical components, i.e. , biomacromolecules, Ca 2+ ions, and water, endow AHIF with properties including biocompatibility and tissue-matching conductivity. These advantages bring light to the application of AHIFs in electrically-conductive implantable devices. As a prototype, an AHIF is designed to perform physioelectrical modulation through noncontact electromagnetic induction. Through experimental and machine learning optimizations, physioelectrical-like signals generated by the AHIF are used to identify the geometry and tension state of the implanted device in the body. Such an intelligent AHIF system has promising application prospects in bioelectronics, IntelliSense, and human-machine interactions.

Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, CUR-BMS1166@ZIF-8@PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity. After entering tumor cells, the pH-sensitive nanoparticles induced autophagy and decreased the intracellular pH, which in turn further facilitated the release of CUR to enhance autophagic activity. Transferring CBZP to orthotopic OS tumor-bearing mice showed powerful antitumor effects and established long-term immunity against tumor recurrence, accompanied by enhanced dendritic cell maturation and tumor infiltration of CD8 + T lymphocytes. Collectively, CBZP exhibited synergistic effects in treating OS by combining ICD induction with checkpoint blockade, thereby shedding light on the use of autophagy control as a potential clinical therapy for OS., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The present study aims to analyse the clinical presentation, treatment and prognosis of a group of patients with orbital cavernous venous malformation (OCVM) with an insidious onset., Method: The clinical data of 35 patients with OCVM treated at our centre between 2003 and 2020 were retrospectively analysed. The OCVMs were classified as one of six types (I-VI) according to the orbital position of the tumour. The clinical characteristics, treatment methods and follow-up results were recorded., Results: A total of 35 patients with OCVM under the optic nerve sheath in the orbital apex area or the common tendon ring (Types I and II) were included in the present study. In 20 cases (57.1%), patients were misdiagnosed with optic neuritis, and in 20 cases (57.1%), the tumour was not identified based on imaging. The presentation was acute or subacute in 23 cases (65.7%). All patients underwent surgery: transnasal surgery in 22 cases (62.9%) and craniotomy in 13 cases (37.1%). A total of 9 patients (25.7%) experienced postoperative complications, and 17 patients (48.6%) experienced vision improvement. The average patient age at first diagnosis was 43.3 ± 10.3 years, and the median follow-up period was 64.5 months. Overall, 14 patients (40%) experienced postoperative complications: postoperative blindness in 6 cases, postoperative vision loss in 8 cases and orbital apex syndrome in 7 cases., Conclusion: Patients with Type I and Type II OCVMs are the most complex cases. They have an insidious onset and are associated with a high rate of misdiagnosis and missed diagnosis. Acute and subacute decreases in visual acuity are mainly caused by OCVM haemorrhage. The difficulty of surgical treatment and the poor prognosis of postoperative vision are characteristics of this tumour. Transnasal surgery and craniotomy can be used to remove OCVMs located in the common tendon ring or optic canal as well as those involving the intracranial area through the supraorbital fissure. Meanwhile, the orbital approach (orbitotomy) has proven to be an effective method of treating OCVMs not involving the deep orbital apex and intracranial area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor, JZ, has declared a shared parent affiliation with the authors at the time of review., (Copyright © 2022 Yang, Li, Liu, Qiu, Zhang, Ren, Jiang, Liu and Kang.)

Vaccination is one of the most effective intervention for the containment and elimination of infectious diseases. Recently, the world's first malaria vaccine RTS, S/AS01 was approved by WHO for use among children living in moderately and highly malaria endemic areas of Africa, which brings a hope for the research and development of malaria vaccines. Here, we review the current status of malaria vaccines development and provide a perspective on the development of next-generation malaria vaccines, so as to provide insights into the successful development of malaria vaccines.

Background: After peripheral nerve injury, Schwann cells proliferate and migrate to the injured site, thereby promoting peripheral nerve regeneration. The process is regulated by various factors. Endothelial cells participate in the process via angiogenesis. However, the effects of endothelial cells on Schwann cells are not yet known. The present study sought to evaluate whether endothelial cells accelerate Schwann cell proliferation and migration., Methods: We established a co-culture model of rat Schwann cells (RSC96s) and rat aortic endothelial cells (RAOECs), and studied the effects of endothelial cells on Schwann cells by evaluating changes in Schwann cell proliferation and migration and related multiple genes and their protein expressions in the co-culture model., Results: The results showed that increasing the proportion of endothelial cells in the co-culture model enhanced the proliferation. At days 1 and 3 following the co-culturing, the relative growth rates of the co-cultured cells were 122.87% and 127.37%, respectively, which showed a significant increase in the viability compared to that of the RSC96s (P<0.05). In this process, the expression of Ki67 increased. The migration ability of Schwann cells was also enhanced. The migration capacity of Schwann cells was detected by wound-healing and Transwell assays. The results of the group with 15% of endothelial cells was significantly higher than the results of the other groups (P<0.0001 and P<0.05, respectively). Further, neuregulin 1 and glial fibrillary acidic protein increased the process of Schwann cell migration., Conclusions: The results showed that endothelial cells can promote the proliferation and migration of Schwann cells and participate in peripheral nerve regeneration., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-81/coif). All authors report that the research was supported by the National Science Foundation of China (No. 81870965). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Night shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers., (© 2021. The Author(s).)

In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although autophagy may be beneficial for maintaining the metabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) and its vitality under inflammation, the underlying mechanism still remains unclear. A previous study found that autophagy activation stimulated the release of exosomes in normal chondrocytes, which are located in a similar avascular environment and share many common features with those of nucleus pulposus cells (NPCs). This study explored the protective effect on matrix degradation in the NP by exosomes derived from autophagy-activated NPCs and exosomal microRNAs. NPCs-derived exosomes (NPCs-Exos) were isolated from culture medium of either normal NPCs or rapamycin-treated NPCs and quantified by nanoparticle tracking analysis. The effect of rapamycin-treated NPC-derived exosomes on NPCs were assessed by coculture with interleukin 1β (IL-1β)-stimulated NPCs. After examination of six major proteinases of the ECM, matrix metalloproteinase 13 (MMP-13) was chosen for further study. miR-27a, which targets MMP-13, was investigated through previous studies and bioinformatics tool. The levels of miR-27a were upregulated in both rapamycin-treated NPCs and their exosomes, compared to the control. When exosomal miR-27a was transferred into NPCs, it alleviated IL-1β-induced degradation of the NPC ECM by targeting MMP-13. Autophagy activation may promote the release of NPCs-derived exosomes and thereby prevent the NPC matrix from degradation. Autophagy activation also alleviates intervertebral disc degeneration (IDD), at least partly via exosomal miR-27a, which restrains MMP-13 expression under IL-1β stimulation. Our work elucidates a new mechanism for how autophagy may participate in preventing IDD, which may be a promising therapeutic strategy., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism., Methods: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs., Results: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings., Conclusions: The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-227). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Decorin (Dcn) is a member of the class I small leucine-rich proteoglycans, whose expression in the nucleus pulposus (NP) of intervertebral discs (IVDs) has been shown to increase with aging in humans and sheep. Dcn induces autophagy in endothelial cells; however, its precise role in NP and IVD degeneration during aging is not well understood. We addressed this question in the present study by treating rat nucleus pulposus cells (NPCs) with different concentrations of Dcn. The Western blot analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling assay results showed that Dcn treatment induced autophagy and decreased apoptosis caused by interleukin (IL)-1β application. This effect was dependent on the protein kinase B/mechanistic target of rapamycin (mTOR)/p70 S6 kinase signaling. Dcn treatment also decreased the expression of matrix metalloproteinase-3 and -13 and decreased the IL-1β-induced attenuation of collagen type II and aggrecan levels. The role of Dcn in stimulating autophagy was further supported by the fact that the observed effects were abrogated by knocking down autophagy-related protein 7 with Atg7 small interfering RNA. Thus, Dcn protects NPCs in IVDs from IL-1β-induced apoptosis and degeneration by promoting autophagy through mTOR signaling., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: This study analyzes two kinds of surgical methods for the treatment of optic pathway gliomas (OPGs) in the intraorbital segment, as well as the surgical outcomes of OPGs., Methods: The clinical data of 86 patients with OPGs treated in our center was analyzed retrospectively, and the clinical symptoms, treatment methods, and follow-up results were recorded., Results: For OPGs in the intraorbital segment, the optic nerve sheath incision was performed to remove a tumor while retaining the optic nerve sheath in Group 1 (n=36). The optic nerve sheath and the tumor were simultaneously removed without retaining the optic nerve sheath in group 2 (n=50). The effects of the design of the surgical methods on the post-surgical outcome are: One patient (1/36, 2.8%) had recurrence in Group 1 and one patient (1/50, 2.0%) had recurrence in group 2. The differences in the surgical outcomes of the two groups regarding exophthalmos, conjunctiva swelling, eye movement disorder, and ptosis were found to be statistically significant (P<0.05). Compared with group 2, the surgical outcomes in the postoperative phase of Group 1 were more satisfactory., Conclusions: The two surgical methods do not increase the recurrence rate of tumors. The resection of OPGs through an optic nerve sheath incision was found to be an ideal surgical method for reducing complications in the postoperative phase and for providing better surgical outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-451). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Mitochondrial optic neuropathy (MON) describes a group of optic neuropathies that exhibit mitochondrial dysfunction in retinal ganglion cells. Pathogenesis of MON includes genetic factors, such as Leber hereditary optic neuropathy and dominant optic atrophy, or acquired factors, such as drug intoxication and nutritional deficiencies, or the combination of both genetic factors and acquired factors. Regardless of different causes, MON shares similar features including bilateral central visual acuity loss, equally normal or slightly sluggish reaction of pupils to light and so on. Many novel therapies, such as pharmacological strategies, genetic therapy and stem cell therapy, are being widely studied in order to limit or reverse the damage of retinal ganglion cells. This article review the pathogenesis, clinical manifestations, ancillary testing, differential diagnosis and treatment progress of MON. (Chin J Ophthalmol, 2021, 57: 386-390) .

Background: This study analyzed the clinical features, imaging manifestations, histopathology, immunohistochemistry, and surgical approaches of the orbital solitary fibrous tumor (OSFT), as well as the factors for postoperative recurrence of such disease., Methods: The clinical data of 16 patients with OSFT treated in our center from 2003 to 2020 were analyzed retrospectively, and the clinical symptoms, treatment methods, and follow-up results were recorded., Results: Of the 16 patients, 8 were females (50.0 %) and 8 were males (50.0 %); the average age of treatment was 37 ± 7 years and the median follow-up time was 74 (8, 228) months. Sixteen patients with OSFT underwent a total of 29 operations, of which 12 were transorbital approach operations and 17 were transfronto-orbital approach operations. Ten patients (10/16, 62.5 %) had recurrence. The recurrence rate of transorbital approach operations was 83.3 % (10/12), and the recurrence rate of transfronto-orbital approach operations was 17.6 % (3/17). No patients had treatment-related complications., Conclusions: The main pathological feature of OSFT is a benign tumor. OSFT has a tendency to grow toward the cranio-orbital junction. The postoperative recurrence rate of OSFT is relatively high, so complete tumor resection is very important for prognosis. Inappropriate surgical approaches can lead to incomplete removal of the tumor and cause recurrence. Choosing the correct operation approach according to the position of the OSFT in the orbit and complete removal of the dura mater and bone affected by the tumor is crucial for the prognosis. Nevertheless, regular long-term follow-up after complete resection is necessary.

Objective: To observe the effects of intravenous methylprednisolone pulse (IVMP) therapy on the recovery of visual acuity and its influencing factors in patients with the relapse of aquaporin (AQP) 4 antibody positive neuromyelitis optica related optic neuritis (NMO-ON). Methods: Retrospective case series. Forty-eight eyes of 35 patients diagnosed as NMO-ON in the Neuro-ophthalmology Clinic of Beijing Tongren Hospital from September 2012 to April 2018 were included in this research. All patients were AQP4 antibody seropositive, and had clinical manifestations of acute optic neuritis, with a history of optic neuritis treated with glucocorticoids effectively. They received the treatment of IVMP 500 mg/d or 1 000 mg/d for 3 to 5 days. The post-treatment and pre-treatment visual acuities were compared. Improving four lines or more was considered as markedly effective, improving two or three lines as effective, and improving one line or no change or a decline as no effect. The impacts of age, visual acuity at onset, relapse rate and dosage on the acute exacerbation of NMO-ON were analyzed. Mann-Whitney U test and Kruskal-Wallis test were used for statistical analysis. Results: Among the 35 patients, there were 2 males and 33 females, aged from 15 to 73 years (median, 36 years). In the 48 eyes of recurrence, the treatment was effective 41.7% (20/48), effective 20.8% (10/48), and ineffective 37.5% (18/48). The IVMP therapy was effective in 25 of 34 eyes with one recurrence and 5 of 14 eyes with two or more recurrences, and the difference was statistically significant ( Z= 2.315, P= 0.021). The efficacy in 13 eyes with preoperative visual acuity not lower than 0.05 (10/13) was better than 35 eyes with preoperative visual acuity lower than 0.05 (20/35), and the difference was statistically significant ( Z= 1.994, P= 0.046). Different ages and doses (1 000 mg/d and 500 mg/d) made no significant difference in the efficacy ( P =0.273,0.105). Conclusions: The IVMP therapy is effective for the NMO-ON relapse in patients who were AQP4 antibody seropositive. The effect of IVMP treatment at doses of 500 mg/d and 1 000 mg/d is similar. Furthermore, visual acuity less than 0.05 and more relapses reduce the efficacy in relapsed NMO-ON patients. (Chin J Ophthalmol, 2020, 56: 509-513) .

There is one circadian clock in the central nervous system and another in the peripheral organs, and the latter is driven by an autoregulatory molecular clock composed of several core clock genes. The height, water content, osmotic pressure and mechanical characteristics of intervertebral discs (IVDs) have been demonstrated to exhibit a circadian rhythm (CR). Recently, a molecular clock has been shown to exist in IVDs, abolition of which can lead to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Autophagy is a fundamental cellular process in eukaryotes and is essential for individual cells or organs to respond and adapt to changing environments; it has also been demonstrated to occur in human NPCs. Increasing evidence supports the hypothesis that autophagy is associated with CR. Thus, we review the connection between CR and autophagy and the roles of these mechanisms in IDD.

The idiopathic optic neuritis (ION) which is related to neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) is called optic neuritis related to neuromyelitis optica (NMO-ON). Because of the high rates of blindness, disability and fatality of NMO, the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic responses, reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed. Currently, detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum is employed as the major supporting approach for the diagnosis of seropositive NMO, however, AQP4-IgG seronegativity in 10% to 25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis. Collaborative international studies hold great promise for establishing and validating biomarkers of NMO. This article discusses known and potential biomarkers for NMO. The biomarkers of NMO maybe the potential biomarkers of NMO-ON, for ION is the initial presentation and the earliest stage. (Chin J Ophthalmol, 2019, 55:228-233) .

Objective: To observe the effect of intravenous methylprednisolone pulse (IVMP) therapy on the recovery of visual acuity and its influencing factors in patients with the first attack of optic neuritis associated with aquaporin-4(AQP4) antibody seropositive neuromyelitis optica. Methods: Retrospective case series study. A total of 165 eyes of 120 patients diagnosed as optic neuritis related to neuromyelitis optica for the first time in the Neuro-ophthalmology Clinic of Beijing Tongren Hospital from September 2012 to December 2017 were selected in this research. All patients had AQP4 antibody seropositivity and clinical manifestations of acute optic neuritis, excluding other diagnoses. All the patients received the treatment of IVMP 500 mg/d or 1 000 mg/d for 3 days, followed by a slowly tapering course of oral glucocorticoids. The post-treatment and pre-treatment visual acuities were compared. Improving four lines or more was considered as effective markedly, improving two or three lines as effective, and improving one line or no change or a decline as no effect. The onset age, visual acuity before treatment and doses in the acute exacerbation were analyzed. The Mann-Whitney U test and Kruskal-Wallis test were used for statistical analyses. Results: Among the 120 patients, there were 17 males and 103 females, with age ranging from 16 to 80 years (median, 44 years). There were 17.6% (29/165) of the eyes with conspicuous therapy, 33.3% (55/165) of the eyes with effective therapy and 49.1% (81/165) of the eyes with ineffective therapy. The effect of IVMP decreased obviously when the age of onset was over 50 years old [41.1%(23/56) vs . 56.0%(61/109), Z= 2.645, P= 0.008]. Patients with no light perception and light perception before treatment had better therapeutic effect than those with counting fingers-0.3 before treatment [72.2%(26/36), 72.7%(24/33) vs . 30.1%(25/83), Z= 2.726, 2.967; P= 0.006, 0.003]. Although the efficacy of patients with visual acuity of onset over 0.3 (9/13) was better than patients with counting fingers-0.3, but the difference was not statistically significant ( Z= 1.743, P= 0.081). Different doses, including IVMP 1 000 mg/d and 500 mg/d, had no significant difference in the effect ( Z= 1.115, P= 0.265). Conclusions: IVMP therapy is only valid for a half of eyes with optic neuritis associated with AQP4 antibody seropositive neuromyelitis optica. The effect of IVMP treatment at doses of 500 mg/d and 1 000 mg/d is similar. Furthermore, the visual acuity from finger counting to 0.3 and age of onset over 50 years old have an influence on the treatment effect. (Chin J Ophthalmol, 2019, 55: 180 - 185) .

Objective: A retrospective study was designed to evaluate the effectiveness of CT-guided core needle biopsy in diagnosing spinal lesions through comparison with C-arm guidance., Methods: From April 2013 to July 2017, a total of 188 patients, who suffered from spinal lesions or had malignant tumor history with a new spinal fracture, were included in this study. There were 96 men and 92 women, with an average of 57.1 years. A total of 238 core needle biopsies were performed. A total of 140 core needle biopsies were carried out under C-arm guidance in 102 patients (group 1); 98 core needle biopsies were carried out under CT guidance in 86 patients (group 2); 108 core needle biopsies were performed in thoracic vertebrae, 116 were in lumbar vertebrae, and 14 were in sacral vertebrae. Seventy-eight patients accepted surgical treatment after biopsies. For these patients, the histological pathologies of the biopsy and surgery were compared to evaluate the accuracy of the biopsy. For the other 110 patients who did not receive surgical treatment, the treatment response and the clinical course were used to evaluate the accuracy of the biopsy. The success rate, the diagnostic accuracy rate, the true positive/negative rate, and complications of the two groups were calculated and compared., Results: There were no significant differences in sex, age, and lesion sites between the C-arm guidance group (group 1) and the CT guidance group (group 2). There were no complications in the two groups. Pathological diagnoses were established in 232 of 238 biopsies. They revealed that 52 were primary malignant tumors, 12 were benign tumors, 70 were metastatic tumors, 4 were tuberculosis, and 94 were classified as "other." The success rate of group 2 was higher than that of group 1, but it was not statistically significant (95.7% vs 100%; P = 0.098). According to the final diagnosis, the diagnostic accuracy rates were calculated and compared. There was no significant difference between the two groups (95.5% vs 96.9%; P = 0.835). The kappa coefficient was used to analyze the concordance between the histological pathologies of the biopsy and the final diagnosis in the two groups. The kappa values of the two group were 0.909 and 0.939, respectively. The results showed good consistency in both groups, but seemed better for group 2., Conclusion: CT-guided core needle biopsy is a relatively safe and effective procedure for diagnosing spinal lesions with a high diagnostic accuracy rate and few complications., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To observe the effect of Guben Zenggu Decoction on the expressions of calmodulin ( CaM ) and calcium/calmodulin-dependent protein kinase Ⅱ ( CaMK Ⅱ) mRNA in the hypothalamus, pituitary, spleen, adrenal gland and femur in ovariectomized rats. To explore the mechanism of Guben Zenggu Decoction regulating and controlling osteoporosis through neuro-endocrine-immune (NEI) network., Methods: The osteoporosis model was established by ovariectomy and randomly divided into model control group, Estradiol valerate group, Guben Zenggu Decoction high, medium and low concentration group. Selected the same age rats as the blank control group, after intervention, 10 rats were randomly selected at the time of 4th, 8th, 12th and 16th weeks from each group, After the success of the model and the successful intervention of Guben Zenggu Decoction for 4, 8, 12 and 16 weeks, the blood were taken from the heart, the serum bone alkaline phosphatase (BALP) levels was measured by the enzyme-linked immunosorbent assay (ELISA), and the thalamus, pituitary, spleen, adrenal, femoral tissue of rats were collected to detected the expressions of CaM and CaMKⅡ mRNA by using real-time fluorescence quantitative polymerase chain reaction (RT-PCR)., Results: At different time points (4 weeks, 8 weeks, 12 weeks, 16 weeks), the expressions of serum BALP and CaM and CaMKⅡ mRNA in NEI network in model group were significantly different from those in blank control group ( P <0.05). Compared with the model control group, serum BALP concentration and CaM mRNA expression in hypothalamus and pituitary tissue were significantly increased in estradiol valerate and Guben Zenggu Decoction groups ( P <0.05). However, the expression of CaM mRNA in adrenal gland, spleen and femur and the expression of CaMKⅡ mRNA in hypothalamus, pituitary, adrenal gland, spleen and femur were significantly decreased ( P <0.05); compared with estradiol valerate group, the effect of Guben Zenggu Decoction on the expressions of CaM mRNA and CaMKⅡ mRNA in femoral and adrenal tissues was significantly different ( P <0.05)., Conclusion: Guben Zenggu Decoction can increase the serum concentration of BALP, regulate the expression of CaM mRNA and CaMKⅡ mRNA in hypothalamus, pituitary, adrenal gland, spleen and femur, thus play a role in prevention and treatment of osteoporosis by regulating NEI network., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Objective: To explore whether bone marrow stem cells (MSCs)-derived exosomes extracted from osteoporosis patients could inhibit osteogenesis via microRNA-21/SMAD7., Patients and Methods: MSCs from osteoporosis patients were isolated and cultured. MSCs morphology was observed, and the specific surface antigens were identified by flow cytometry. The osteogenic ability of MSCs was detected by alizarin red staining and oil red staining. Exosomes were collected from MSCs suspension by ultracentrifugation, and microRNA-21 expression in MSCs derived-exosomes was detected. Moreover, protein and mRNA levels of ALP, Bglap, and Runx2 in MSCs treated with different sources of MSCs-derived exosomes were detected by qRT-PCR (quantitative real-time polymerase chain reaction) and Western blot, respectively. ALP activity in MSCs was accessed by a relative commercial kit. Furthermore, binding sites of microRNA-21 and SMAD7 were predicted by Targetscan, miRWalk, and miRDB, and were further verified by luciferase reporter gene assay. SMAD7 expression in MSCs derived-exosomes was also detected., Results: MSCs extracted from healthy adults, and osteoporosis patients were in adherent growth and exhibited elongated morphology, which could differentiate into osteoblasts and lipoblasts after different inductions. MicroRNA-21 expression in MSCs-derived exosomes extracted from osteoporosis patients was remarkably higher than those extracted from healthy adults. Decreased Runx2 expression and ALP activity were found after treatment of MSCs-derived exosomes extracted from osteoporosis patients. SMAD7 was confirmed to bind to microRNA-21 and was downregulated in osteoporosis patients in comparison with healthy adults. Overexpression of SMAD7 resulted in downregulated ALP, Bglap, and Runx2., Conclusions: MicroRNA-21 inhibits osteogenesis through regulating MSCs-derived exosomes extracted from osteoporosis patients via targeting SMAD7.

Objective: Nowadays, it is still questionable whether denatured collagen (DCol) can replace the native collagen (Col) as a bioactive protein in cartilage engineering. We sought to study the advantages of Col with a triple-helical structure in the collagen-based composite materials for cartilage engineering., Methods: We presented new three-dimensional (3D) Col and DCol scaffolds with shape memory properties. The effects of Col and DCol scaffolds on rabbit chondrocytes' proliferation, adhesion, differentiation and interaction with matrix were investigated. Tissue compatibility was performed in a subcutaneous Sprague Dawley (SD) rat model. The repair ability of different scaffolds with chondrocytes for full-thickness articular cartilage defects in knee joints of New Zealand white rabbits were investigated., Results: The results indicated that the Col scaffolds (with concentration 1.6wt% and 0.8wt%, respectively) promoted the proliferation, adhesion and redifferentiation of chondrocytes, as well as chondrocyte-matrix interaction, to a greater degree than the DCol scaffolds. In the animal experiment, the Col scaffolds filled in the defect hole significantly maintained chondrocytes function, promoted cartilage and subchondral bone regeneration, compared with the DCol scaffolds, and the scaffolds loaded with chondrocytes were better than the cell-free scaffolds, especially in the case of the Col scaffolds (1.6 wt%)., Conclusions: Taken together, these insights suggest that the better proliferation, adhesion and redifferentiation of chondrocytes in Col scaffolds with the triple-helical structure may contribute to the greater cartilage repair ability. Col scaffolds may be more appropriate for repairing cartilage defects than DCol scaffolds, and DCol cannot as an alternative when using collagen-based materials for cartilage engineering applications., (Copyright © 2018. Published by Elsevier Ltd.)

Trauma remains a tremendous medical burden partly because of increased expenditure for the management of multiple organ dysfunction syndrome (MODS) developed during hospital stay. The intestinal barrier injury continues to be a second insult resulting in MODS which currently lacks efficient strategies for prevention. Recent studies have uncovered multi-organ protective benefits of atrial natriuretic peptide (ANP) in cardiovascular disease. However, the role of ANP in the prevention of MODS following severe trauma has not been understood. In our laboratory study, 1-h infusion of exogenous ANP during hemorrhagic shock following severe trauma induced high-level expression of endogenous serum ANP after 24 h, this effect was related to the improved level of functional biomarkers in multiple organs. Such phenomenon has not been found in other laboratories. A thorough literature review consequently was performed to uncover the potential mechanisms, to appraise therapy safety, and to propose uncertainties. In severe trauma, short-term exogenous ANP therapy during hemorrhagic shock may promote sustained endogenous expression of ANP from intestinal epithelium through activating a positive feedback loop mechanism involving phospholipase C-γ1 and reactive oxygen species crosstalk. This feedback loop may prevent MODS through multiple signaling pathways. Administration of ANP during hemorrhagic shock is thought to be safe. Further studies are required to confirm our proposed mechanisms and to investigate the dose, duration, and timing of ANP therapy in severe trauma.