Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT (OFT)) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor (BPTF) to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA-tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24-/-) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

A novel rat model of annulus fibrosus injury for intervertebral disc degeneration.

BACKGROUND CONTEXT: In clinical practice, acute trauma and chronic degeneration of the annulus fibrosus (AF) can promote further degeneration of the intervertebral disc (IVD). Therefore, it is critical to understand the AF repair process and its consequences on IVD. However, the lack of cost-effective and reproducible in vivo animal models of AF injury has limited research development in this field. PURPOSES: The purpose of this study was to establish and evaluate the utility of a novel animal model for full-thickness AF injury. Three foci were proposed: (1) whether this new modeling method can cause full-layer AF damage; (2) the repair processes and pathological changes in the damaged area after AF injury, and (3) the morphological and histological changes in the IVD are after AF injury. STUDY DESIGN/SETTING: In vivo rat AF injury model with characterization of AF damage repair, IVD degeneration. METHODS: A total of 72,300 g male rats were randomly assigned to one of the two groups: experimental or sham. Annulus fibrosus was separated layer by layer under the microscope with a #11 blade up to the AF- nucleus pulpous (NP) junction. The repair process of the horizontal AF and morphological changes in the sagittal IVD were evaluated with HE staining. Sirius red staining under polarized light. Immunofluorescence was conducted to analyze changes in the expression of COL1 and COL3 in the AF injury area and 8-OHdg, IL-6, MMP13, FSP1, and ACAN in the IVD. The disc height and structural changes after AF injury were measured using X-ray and contrast-enhanced micro-CT. Additionally, the resistance of the AF to stretching was analyzed using three-point bending. RESULTS: Annulus fibrosus-nucleus pulpous border was identified to stably induce the full-thickness AF injury without causing immediate NP injury. The AF repair process after injury was slow and expressed inflammation factors continuously, with abundant amounts of type III collagen appearing in the inner part of the AF. The scar at the AF lesion had decreased resistance to small molecule penetration and weakened tensile strength. Full-thickness AF injury induced disc degeneration with loss of disc height, progressive unilateral vertebral collapse, and ossification of the subchondral bone. Inflammatory-induced degeneration and extracellular matrix catabolism gradually appeared in the NP and cartilage endplate (CEP). CONCLUSIONS: We established a low-cost and reproducible small animal model of AF injury which accurately replicated the pathological state of the limited AF self-repair ability and demonstrated that injury to the AF alone could cause further degeneration of the IVD. CLINICAL RELEVANCE: This in vivo rat model can be used to study the repair process of the AF defect and pathological changes in the gradual degeneration of IVD after AF damage. In addition, the model provides an experimental platform for in vivo experimental research of potential clinical therapeutics.

Comparison of Intraoperative Endplate Injury between Mini-Open Lateral Lumbar Interbody Fusion (LLIF) and Transforaminal Lumbar Interbody Fusion (TLIF) and Analysis of Risk Factors: A Retrospective Study.

OBJECTIVE: The study aimed to compare the incidence of intraoperative endplate injury in patients who underwent Transforaminal interbody fusion (TLIF) and mini-open lumbar interbody fusion (LLIF) surgery. The independent risk factors related to endplate injury in LLIF procedure were analyzed. METHODS: A total of 199 patients who underwent LLIF (n = 106) or TLIF (n = 93) surgery from June 2019 to September 2021 were reviewed. The endplate injury was assessed by postoperative sagittal CT scan. A binary logistic analysis model were used to identify independent risk factors related to LLIF endplate injury based on univariate analysis. RESULTS: There was an obvious difference in the occurrence of intraoperative endplate injury between LLIF (42/106, 39.6%) and TLIF group (26/93, 28%), although it did not reach the significant level. L1 CT value (OR = 0.985, 95% CI = 0.972-0.998), cage position (OR = 3.881, 95% CI = 1.398-10.771) and height variance (OR = 1.263, 95% CI = 1.013-1.575) were independent risk factors for endplate injury in LLIF procedure. According to the cage settlement patterns, there 5 types of A to E. The severity of the facet joint degeneration was positively related to the occurrence of endplate injury. CONCLUSIONS: The incidence of intraoperative endplate injury is higher in LLIF than in TLIF procedures. Low bone quantity, cage posterior position and larger height variance are risk factors to induce endplate injury in LLIF surgery. The facet joint degeneration may be related to severe endplate injuries and even fractures.

Thermosensitive hydrogel-based GPR124 delivery strategy for rebuilding blood-spinal cord barrier.

Spinal cord injury (SCI) causes blood-spinal cord barrier (BSCB) disruption, leading to secondary damage, such as hemorrhagic infiltration, inflammatory response, and neuronal cell death. It is of great significance to rebuild the BSCB at the early stage of SCI to alleviate the secondary injury for better prognosis. Yet, current research involved in the reconstruction of BSCB is insufficient. Accordingly, we provide a thermosensitive hydrogel-based G protein-coupled receptor 124 (GPR124) delivery strategy for rebuilding BSCB. Herein, we firstly found that the expression of GPR124 decreased post-SCI and demonstrated that treatment with recombinant GPR124 could partially alleviate the disruption of BSCB post-SCI by restoring tight junctions (TJs) and promoting migration and tube formation of endothelial cells. Interestingly, GPR124 could also boost the energy metabolism of endothelial cells. However, the absence of physicochemical stability restricted the wide usage of GPR124. Hence, we fabricated a thermosensitive heparin-poloxamer (HP) hydrogel that demonstrated sustained GPR124 production and maintained the bioactivity of GPR124 (HP@124) for rebuilding the BSCB and eventually enhancing functional motor recovery post-SCI. HP@124 hydrogel can encapsulate GPR124 at the lesion site by injection, providing prolonged release, preserving wounded tissues, and filling injured tissue cavities. Consequently, it induces synergistically efficient integrated regulation by blocking BSCB rupture, decreasing fibrotic scar formation, minimizing inflammatory response, boosting remyelination, and regenerating axons. Mechanistically, giving GPR124 activates energy metabolism via elevating the expression of phosphoenolpyruvate carboxykinase 2 (PCK2), and eventually restores the poor state of endothelial cells. This research demonstrated that early intervention by combining GPR124 with bioactive multifunctional hydrogel may have tremendous promise for restoring locomotor recovery in patients with central nervous system disorders, in addition to a translational approach for the medical therapy of SCI.

Controlled extracellular vesicles release from aminoguanidine nanoparticle-loaded polylysine hydrogel for synergistic treatment of spinal cord injury.

Pharmaceutical treatments are critical for the acute and subacute phases of spinal cord injury (SCI) and significantly impact patients' prognoses. However, there is a lack of a precise, multitemporal, integrated drug delivery system for medications administered in both phases. In this study, we prepare a hybrid polylysine-based hydrogel (PBHEVs@AGN) comprising short-term release of pH-responsive aminoguanidine nanoparticles (AGN) and sustained release of extracellular vesicles (EVs) for synergistic SCI treatment. When AGN is exposed to the acidic environment at the injury site, it quickly diffuses out of the hydrogel and releases the majority of the aminoguanidine within 24 h, reducing oxidative stress in lesion tissues. Enriched EVs are gradually released from the hydrogel and remain in the tissue for weeks, providing a long-term anti-inflammatory effect and further ensuring axonal regeneration. Fast-releasing aminoguanidine can cooperate with slow-release EVs to treat SCI more effectively by reducing the production of proinflammatory cytokines and blocking the TLR4/Myd88/NF-κB inflammatory pathway, creating a sustained anti-inflammatory microenvironment for SCI recovery. Our in vivo experiments demonstrate that PBHEVs@AGN reduces the occurrence of scar tissue, encourages remyelination, and speeds up axonal regeneration. Herein, this multi-drug delivery system, which combines the acute release of aminoguanidine and the sustained release of EVs is highly effective for synergistically managing the challenging pathological processes after SCI.

Silicate Nanoplatelets Promotes Neuronal Differentiation of Neural Stem Cells and Restoration of Spinal Cord Injury.

Neural stem cell (NSC) transplantation has been suggested as a promising therapeutic strategy to replace lost neurons after spinal cord injury (SCI). However, the low survival rate and neuronal differentiation efficiency of implanted NSCs within the lesion cavity limit the application. Furthermore, it is difficult for transplanted cells to form connections with host cells. Thus, effective and feasible methods to enhance the efficacy of cell transplantation are needed. In this study, the effect of Laponite nanoplatelets, a type of silicate nanoplatelets, on stem cell therapy is explored. Laponite nanoplatelets can induce the neuronal differentiation of NSCs in vitro within five days, and RNA sequencing and protein expression analysis demonstrated that the NF-κB pathway is involved in this process. Moreover, histological results revealed that Laponite nanoplatelets can increase the survival rate of transplanted NSCs and promote NSCs to differentiate into mature neurons. Finally, the formation of connections between transplanted cells and host cells is confirmed by axon tracing. Hence, Laponite nanoplatelets, which drove neuronal differentiation and the maturation of NSCs both in vitro and in vivo, can be considered a convenient and practical biomaterial to promote repair of the injured spinal cord by enhancing the efficacy of NSC transplantation.

Postural deformities in Parkinson's disease: A bibliometric analysis based on web of science.

Objective: Postural deformities are common debilitating conditions during the progression of Parkinson's disease (PD). However, the underlying pathophysiology and optimal treatment strategy are unclear. In this study, we aimed to identify primary research fields, important achievements and emerging trends in postural deformities in PD. Methods: Web of Science Core Collection database was searched to retrieve all literature related to postural deformities in PD over the past 20 years. Data such as annual numbers of publications, countries of origin, publication journals, cooperation between countries, citation index and keywords were retrieved from the selected publications. Bibliometrix Package in R software were used for bibliometric analysis and visualization. Results: In total, 211 publications that met the criteria were collected. Analyses had shown that the annual numbers of publications increased gradually with fluctuations. Japan was the most prolific country (n = 59). Italy participated in international cooperation the most frequently. Parkinsonism & related disorders (n = 25) took a prominent lead among all journals, and the most productive institution in this area was University of Verona (n = 27). The most local cited author was Tinazzi Michele. According to the thematic map, "scoliosis", "fusion", and "balance" have rapidly become research hot spots in related fields. Conclusions: Articles pertaining to postural deformities in PD are still being published, in which the etiology is a combination of peripheral plus central involvement. Treatment approaches include rehabilitative exercises, oral medication, botulinum toxin injection, deep brain stimulation and spine surgery, which is getting current attention and would be a hot topic of future research.

Long-term measles antibody profiles following different vaccine schedules in China, a longitudinal study.

Characterizing the long-term kinetics of maternally derived and vaccine-induced measles immunity is critical for informing measles immunization strategies moving forward. Based on two prospective cohorts of children in China, we estimate that maternally derived immunity against measles persists for 2.4 months. Following two-dose series of measles-containing vaccine (MCV) at 8 and 18 months of age, the immune protection against measles is not lifelong, and antibody concentrations are extrapolated to fall below the protective threshold of 200 mIU/ml at 14.3 years. A catch-up MCV dose in addition to the routine doses between 8 months and 5 years reduce the cumulative incidence of seroreversion by 79.3-88.7% by the age of 6 years. Our findings also support a good immune response after the first MCV vaccination at 8 months. These findings, coupled with the effectiveness of a catch-up dose in addition to the routine doses, could be instrumental to relevant stakeholders when planning routine immunization schedules and supplemental immunization activities.

Metabolic Glycoengineering: A Promising Strategy to Remodel Microenvironments for Regenerative Therapy.

Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called "microenvironments." Among the various factors in the microenvironment, the cell-surface glycan acts as a mediator of cell-matrix and cell-cell interactions and manipulates the behavior of cells. Herein, metabolic glycoengineering (MGE) is an easy but powerful technology for remodeling the structure of glycan. By presenting unnatural glycans on the surface, MGE provides us an opportunity to reshape the microenvironment and evoke desired cellular responses. In this review, we firstly focused on the determining role of glycans on cellular activity; then, we introduced how MGE influences glycosylation and subsequently affects cell fate; at last, we outlined the application of MGE in regenerative therapy, especially in the musculoskeletal system, and the future direction of MGE is discussed.

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering.

Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells. Bioscaffolds fabricated based on the ECM synthesis functions of NPCs have possible roles in cell transplantation and differentiation induction, but it has not been studied. In this study, we first aggregated NPCs into pellets, and then, NPC-derived efficient microcarriers (NPCMs) were fabricated by pellet cultivation under specific conditions and optimized decellularization. Thirdly, we evaluated the microstructure, biochemical composition, biostability and cytotoxicity of the NPCMs. Finally, we investigated the NP-specific differentiation of ADSCs induced by the NPCMsin vitroand NP regeneration induced by the ADSC-loaded NPCMs in a rabbit model. The results indicated that the injectable NPCMs retained maximal ECM and minimal cell nucleic acid after optimized decellularization and had good biostability and no cytotoxicity. The NPCMs also promoted the NP-specific differentiation of ADSCsin vitro. In addition, the results of MRI, x-ray, and the structure and ECM content of NP showed that the ADSCs-loaded NPCMs can partly restored the degenerated NPin vivo. Our injectable NPCMs regenerated the degenerated NP and provide a simplified and efficient strategy for treating IVD degeneration.

Surgical technique modification of circumferential decompression for thoracic spinal stenosis and clinical outcome.

Progressive thoracic myelopathy caused by ossification of posterior longitudinal ligament (OPLL) responds poorly to conservative therapy. The most direct decompression is extirpation of ossified posterior longitudinal ligament (PLL). Surgical outcomes of posterior approaches to remove ossified PLL are not always satisfactory because of the risk of neurological deterioration. In this study, we modified the conventional anterior decompression technique via a posterior approach for thoracic OPLL. From an anterior approach, the posterior cortex of vertebral body was exposed and the ossified PLL was removed. Then kyphosis correction was done via posterior instrumentation to reduce cord compression between dura under tension and the anterior canal wall. From the back, the distal end of the ossified PLL was displaced anteriorly to create a gap between ossified PLL and dura, remaining adhesions were divided and the ossified PLL was manipulated through this gap under direct vision. The surgical technique was applied in 20 patients with thoracic myelopathy caused by OPLL. One case of postoperative neurological deterioration was encountered but this recovered fully. Our outcomes were relatively favorable.

Direct Reprogramming in Bone and Joint Degenerative Diseases: Applications, Obstacles and Directions.

With a booming aging population worldwide, bone and joint degenerative diseases have gradually become a major public health focus, attracting extensive scientific attention. However, the effective treatments of these degenerative diseases have been confined to traditional medications and surgical interventions, which easily lead to the possibility of drug abuse or loss of physiological function to varying degrees. Recently, given that the development of reprogramming has overcome shackles in the field of degenerative diseases, direct reprogramming would provide a new concept to accelerate progress in the therapy of bone and joint degenerative diseases. The process of direct reprogramming would directly induce ordinary somatic cells to the desired targeted cells without passing through pluripotent cell states. In this review, we summarize some direct reprogramming of cells that has been attempted for the repair of common bone and joint degenerative diseases, such as osteoarthritis, osteoporosis-related fracture and intervertebral disc degeneration. However, it is inevitable that some obstacles, such as accurate transcription factors, an appropriate extracellular microenvironment and efficient delivery carriers in vivo, need to be resolved. In addition, developmental and promising directions associated with direct reprogramming have attracted public attention. Investigation of the regulation of the transient genome, metabolic conversion and cellular skeleton would provide superior potential candidates for the revolution of direct reprogramming. The aim of direct reprogramming is to directly provide target cells for cell therapy and even tissue reconstruction in bone and joint degenerative diseases. Moreover, the development of direct reprogramming have potential to achieve repair and even reconstruct in situ, which would be breakthrough effect for the repair of bone and joint degenerative diseases. The advance of direct reprogramming has opened numerous opportunities for new therapeutic strategies in regenerative medicine.

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels.

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide-co-acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.

An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration.

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Transmission Pattern of Measles Virus Circulating in China During 1993-2021: Genotyping Evidence Supports That China Is Approaching Measles Elimination.

BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.

Collagen Niches Affect Direct Transcriptional Conversion toward Human Nucleus Pulposus Cells via Actomyosin Contractility.

Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs). Next, tunable physical properties of collagen niches are fabricated based on various crosslinking degrees. Collagen niches significantly affect actomyosin cytoskeleton and then influence the maturation of iNPLCs. Using gain- and loss of function approaches, the appropriate physical states of collagen niches are found to significantly enhance the maturation of iNPLCs through actomyosin contractility. Moreover, in a rat model of degenerative disc diseases, iNPLCs with collagen niches are transplanted into the lesion to achieve significant improvements. As a result, overexpression of transcription factors in human dermal fibroblasts are efficiently converted into iNPLCs and the optimal collagen niches affect cellular cytoskeleton and then facilitate iNPLCs maturation toward human nucleus pulposus cells. These findings encourage more in-depth studies toward the interactions of niches and direct conversion, which would contribute to the development of direct conversion.

Importation and circulation of rubella virus lineages 1E-L2 and 2B-L2c between 2018 and 2021 in China: Virus evolution and spatial-temporal transmission characteristics.

To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018-9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide.

Cervical rotational osteotomy for correction of axial deformity in a patient with ankylosing spondylitis.

PURPOSE: Severe cervical axial deformity associated with ankylosing spondylitis (AS) is rare in clinic, and there are little concerns about surgical treatment of axial deformity associated with AS. The case study aims to show the surgical technique to perform cervical rotational osteotomy. METHODS: We present the case of a young AS patient whose neck was fixed in a left-rotational posture at 18°, requiring his trunk to be turned to the right to look forward visually. This made his gait appear to be limping, inconveniencing him with great difficulty. In order to correct this deformity, we performed a novel cervical rotational osteotomy through a one-stage posterior-anterior-posterior approach. Firstly, we performed laminectomies of C7 and T1, followed by a C7/T1 facetectomy with release of the bilateral C8 nerve roots. Next, we performed C7/T1 discectomy, bony resection of the lateral body and uncovertebral joints. The head of the patient was then rotated manually, so that both his face and torso were simultaneously facing frontward. Finally, rods spanning the screws from C6 to T2 were fixed. RESULTS: Postoperatively, the patient's axial malalignment was significantly improved, and he was able to walk normally. Surgical outcomes were well maintained at a 3-year follow-up. CONCLUSION: Through this case, we hope to draw the attention to spinal axial deformity and provide a reference point in the surgical treatment of spinal axial deformity.