A Trisomy 21-linked Hematopoietic Gene Variant in Microglia Confers Resilience in Human iPSC Models of Alzheimer's Disease.

While challenging, identifying individuals displaying resilience to Alzheimer's disease (AD) and understanding the underlying mechanism holds great promise for the development of new therapeutic interventions to effectively treat AD. Down syndrome (DS), or trisomy 21, is the most common genetic cause of AD. Interestingly, some people with DS, despite developing AD neuropathology, show resilience to cognitive decline. Furthermore, DS individuals are at an increased risk of myeloid leukemia due to somatic mutations in hematopoietic cells. Recent studies indicate that somatic mutations in hematopoietic cells may lead to resilience to neurodegeneration. Microglia, derived from hematopoietic lineages, play a central role in AD etiology. We therefore hypothesize that microglia carrying the somatic mutations associated with DS myeloid leukemia may impart resilience to AD. Using CRISPR-Cas9 gene editing, we introduce a trisomy 21-linked hotspot CSF2RB A455D mutation into human pluripotent stem cell (hPSC) lines derived from both DS and healthy individuals. Employing hPSC-based in vitro microglia culture and in vivo human microglia chimeric mouse brain models, we show that in response to pathological tau, the CSF2RB A455D mutation suppresses microglial type-1 interferon signaling, independent of trisomy 21 genetic background. This mutation reduces neuroinflammation and enhances phagocytic and autophagic functions, thereby ameliorating senescent and dystrophic phenotypes in human microglia. Moreover, the CSF2RB A455D mutation promotes the development of a unique microglia subcluster with tissue repair properties. Importantly, human microglia carrying CSF2RB A455D provide protection to neuronal function, such as neurogenesis and synaptic plasticity in chimeric mouse brains where human microglia largely repopulate the hippocampus. When co-transplanted into the same mouse brains, human microglia with CSF2RB A455D mutation phagocytize and replace human microglia carrying the wildtype CSF2RB gene following pathological tau treatment. Our findings suggest that hPSC-derived CSF2RB A455D microglia could be employed to develop effective microglial replacement therapy for AD and other age-related neurodegenerative diseases, even without the need to deplete endogenous diseased microglia prior to cell transplantation.

[Treatment of open fracture bone defect of distal femur with antibiotic cement column and bone graft].

OBJECTIVE: To investigate the efficacy of antibiotic cement column combined with iliac bone graft in the treatment of open fracture with bone defect of distal femur. METHODS: From October 2014 to March 2021, 16 patients of open fracture bone defect of distal femur were treated with antibiotic bone cement column and iliac bone graft, including 12 males and 4 females. The age ranged from 28 to 68 years old. There were 11 cases of traffic accident injury, 5 cases of falling injury, 3 cases as Gustilo type Ⅰ, 5 cases as type Ⅱ and 8 cases as type ⅢA. AO classification was used:9 cases of C2 type and 7 cases of C3 type. The time from injury to final bone grafting ranged from 4 to 119 days. The length of bone defect ranged from 2 to10 cm. Fractures healing time, complications and knee function Merchan score were recorded. RESULTS: All the 16 patients were followed up from 9 to 29 months. The incisions of 16 patients healed in one stage without postoperative infection, plate fracture, limb shortening and valgus and varus deformity. The healing time randed from 4 to 10 months . Knee joint function according to the Merchant scoring standard, showed that 8 cases were excellent, 4 cases were good, 3 cases were fair, and 1 case was poor. CONCLUSION: The use of antibiotic bone cement column combined with iliac bone graft in the treatment of open and complex bone defects of distal femur is an effective surgical method to prevent infection, assist fracture reduction, increase fixation strength and significantly reduce the amount of bone grafting.

Comparison of Locking Plate Alone and Locking Plate Combined with 3D Printed Polymethylmethacrylate Augmentation in Treating Proximal Humerus Fractures in the Elderly.

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

Gene editing-based targeted integration for correction of Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from a diversity of mutations distributed across all 12 exons of the WAS gene. WAS encodes a hematopoietic-specific and developmentally regulated cytoplasmic protein (WASp). The objective of this study was to develop a gene correction strategy potentially applicable to most WAS patients by employing nuclease-mediated, site-specific integration of a corrective WAS gene sequence into the endogenous WAS chromosomal locus. In this study, we demonstrate the ability to target the integration of WAS2-12-containing constructs into intron 1 of the endogenous WAS gene of primary CD34+ hematopoietic stem and progenitor cells (HSPCs), as well as WASp-deficient B cell lines and WASp-deficient primary T cells. This intron 1 targeted integration (TI) approach proved to be quite efficient and restored WASp expression in treated cells. Furthermore, TI restored WASp-dependent function to WAS patient T cells. Edited CD34+ HSPCs exhibited the capacity for multipotent differentiation to various hematopoietic lineages in vitro and in transplanted immunodeficient mice. This methodology offers a potential editing approach for treatment of WAS using patient's CD34+ cells.

Regulatory mechanisms of autophagy-related ncRNAs in bone metabolic diseases.

Bone metabolic diseases have been tormented and are plaguing people worldwide due to the lack of effective and thorough medical interventions and the poor understanding of their pathogenesis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that cannot encode the proteins but can affect the expressions of other genes. Autophagy is a fundamental mechanism for keeping cell viability, recycling cellular contents through the lysosomal pathway, and maintaining the homeostasis of the intracellular environment. There is growing evidence that ncRNAs, autophagy, and crosstalk between ncRNAs and autophagy play complex roles in progression of metabolic bone disease. This review investigated the complex mechanisms by which ncRNAs, mainly micro RNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate autophagic pathway to assist in treating bone metabolism disorders. It aimed at identifying the autophagy role in bone metabolism disorders and understanding the role, potential, and challenges of crosstalk between ncRNAs and autophagy for bone metabolism disorders treatment.

Proteomic Analysis Based on TMT Regarding the Therapeutic Action of Rhizoma Drynariae on Rats in an Osteoporosis Model.

BACKGROUND: Primary osteoporosis has increasingly become one of the risk factors affecting human health, and the clinical effect and action mechanism of traditional Chinese medicine in the treatment of primary osteoporosis have been widely studied. Previous studies have confirmed that in traditional Chinese medicine (TCM), Drynaria rhizome has a role in improving bone density. In this study, a tandem mass tag (TMT)-based proteomic analysis was conducted to derive potential targets for Drynaria rhizome treatment in postmenopausal osteoporosis. METHODS: The model group (OVX) and experimental group (OVXDF) for menopausal osteoporosis were established using the universally acknowledged ovariectomy method, and the OVXDF group was given 0.48g/kg Rhizoma Drynariae solution by gavage for 12 weeks. After 12 weeks, femurs of rats selected for this study were examined with a bone mineral density (BMD) test, Micro-CT, ELISABiochemical testing, hematoxylin and eosin (HE) staining, and immunohistochemistry. A certain portion of the bone tissue was studied with a TMT-based proteomic analysis and functional and pathway enrichment analysis. Finally, key target genes were selected for Western blotting for validation. RESULTS: The comparison of the OVXDF and OVX groups indicated that Drynaria rhizome could improve bone density. In the TMT-based proteomic analysis, the comparison of these two groups revealed a total of 126 differentially expressed proteins (DEPs), of which 62 were upregulated and 64 were downregulated. Further, by comparing the differential genes between the OVXDF and OVX groups and between the OVX and SHAM groups, we concluded that the 27 differential genes were significantly changed in the rats selected for the osteoporosis model after Drynaria rhizome intragastric administration. The gene ontology (GO) enrichment analysis of DEPs showed that molecular function was mainly involved in biological processes, such as glucose metabolism, carbohydrate metabolism, immune responses, and aging. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEPs revealed that multiple differential genes were enriched in the estrogen and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Relationships with nitrogen metabolism, glycerophospholipid metabolism, secretion systems, and tumor diseases were also observed. Western blotting was consistent with the analysis. CONCLUSIONS: We used TMT-based proteomics to analyze the positive effects of TCM Drynaria rhizome, which can regulate related proteins through the unique roles of multiple mechanisms, targets, and pathways. This treatment approach can regulate oxidative stress, improve lipid metabolism, reduce the inflammatory response mechanism, and improve bone density. These benefits highlight the unique advantages of TCM in the treatment of primary osteoporosis.

Comparative Analysis of Structural Composition and Function of Intestinal Microbiota between Chinese Indigenous Laiwu Pigs and Commercial DLY Pigs.

Intestinal microbiota has an important impact on pig phenotypes. Previous studies mainly focused on the microbiota of feces and worldwide farmed commercial pigs, while research on the microbiota of various intestinal sections and indigenous pig breeds is very limited. This study aimed to characterize and compare the biogeography of intestinal microbiota in pigs of one Chinese indigenous breed and one commercial crossbred. In this study, we sequenced the microbiota of six intestinal segments in the grown-up pigs of a Chinese indigenous breed, Laiwu pigs, and the worldwide farmed crossbred Duroc × Landrace × Yorkshire (DLY) pigs by 16S rRNA sequencing, characterized the biogeography of intestinal microbiota, and compared the compositional and functional differences between the two breeds. The results showed that there were obvious differences in microbial structure and abundance between the small and large intestines. Laiwu pigs had higher large intestinal diversity than DLY pigs, while DLY pigs had higher small intestinal diversity than Laiwu pigs. Moreover, some specific bacterial taxa and Kyoto Encyclopedia of Genes and Genomes pathways were found to be related to the high fat deposition and good meat quality of Laiwu pigs and the high growth speed and lean meat rate of DLY pigs. This study provides an insight into the shifts in taxonomic composition, microbial diversity, and functional profile of intestinal microbiota in six intestinal segments of Laiwu and DLY pigs, which would be essential for exploring the potential influence of the host's genetic background on variation in microbiota composition and diversity.

The Wiskott-Aldrich syndrome protein is required for positive selection during T-cell lineage differentiation.

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency caused by a mutation in the WAS gene. This leads to altered or absent WAS protein (WASp) expression and function resulting in thrombocytopenia, eczema, recurrent infections, and autoimmunity. In T cells, WASp is required for immune synapse formation. Patients with WAS show reduced numbers of peripheral blood T lymphocytes and an altered T-cell receptor repertoire. In vitro, their peripheral T cells show decreased proliferation and cytokine production upon aCD3/aCD28 stimulation. It is unclear whether these T-cell defects are acquired during peripheral activation or are, in part, generated during thymic development. Here, we assessed the role of WASp during T-cell differentiation using artificial thymic organoid cultures and in the thymus of humanized mice. Although CRISPR/Cas9 WAS knockout hematopoietic stem and progenitor cells (HSPCs) rearranged the T-cell receptor and differentiated to T-cell receptor (TCR)+ CD4+ CD8+ double-positive (DP) cells similar to wild-type HSPCs, a partial defect in the generation of CD8 single-positive (SP) cells was observed, suggesting that WASp is involved in their positive selection. TCR repertoire analysis of the DP and CD8+ SP population, however, showed a polyclonal repertoire with no bias toward autoreactivity. To our knowledge, this is the first study of the role of WASp in human T-cell differentiation and on TCR repertoire generation.

Correlation Analysis between Residual Pain after Vertebral Augmentation and the Diffusion Distribution of Bone Cement: A Retrospective Cohort Study.

Objective: To explore the influence and potential factors of the bone cement dispersion state on residual pain after vertebral augmentation. Methods: The cases included in this retrospective cohort study were patients treated with vertebral augmentation (VA) for osteoporotic vertebral compression fractures (OVCFs) between July 2018 and June 2021. According to the type of cement diffusion distribution, the patients were divided into a sufficient diffusion group (Group A) and an insufficient diffusion group (Group B). The differences in the baseline data, visual analog scale (VAS), Oswestry disability index score (ODI), injured vertebral height (IVH), and local kyphosis angle (LKA) between the two groups were analyzed. Assessments were performed preoperatively on the 2nd day postoperation and at the last follow-up. The imaging data of injured vertebrae were accurately reconstructed by a GE AW4.7 workstation, and the differences in the vertebral body volume, bone cement volume, and bone cement volume ratio were compared between the groups. Result: After screening, 36 patients were included. (1) The postoperative VAS and ODI scores of the two groups were significantly improved compared with the preoperative scores. (2) On the 2nd day postoperation and the last follow-up, the VAS and ODI scores of Group A were significantly different from those of Group B, and Group A outperformed Group B. (3) The IVH and LKA of the two groups were improved after the operation, and no significant difference was found between the groups. (4) Significant differences were found in the bone cement volume and bone cement volume ratio between the groups, and Group A was larger than Group B. Conclusions: Sufficient bone cement diffusion can reduce residual pain after vertebral augmentation.

Autophagy: An important target for natural products in the treatment of bone metabolic diseases.

Bone homeostasis depends on a precise dynamic balance between bone resorption and bone formation, involving a series of complex and highly regulated steps. Any imbalance in this process can cause disturbances in bone metabolism and lead to the development of many associated bone diseases. Autophagy, one of the fundamental pathways for the degradation and recycling of proteins and organelles, is a fundamental process that regulates cellular and organismal homeostasis. Importantly, basic levels of autophagy are present in all types of bone-associated cells. Due to the cyclic nature of autophagy and the ongoing bone metabolism processes, autophagy is considered a new participant in bone maintenance. Novel therapeutic targets have emerged as a result of new mechanisms, and bone metabolism can be controlled by interfering with autophagy by focusing on certain regulatory molecules in autophagy. In parallel, several studies have reported that various natural products exhibit a good potential to mediate autophagy for the treatment of metabolic bone diseases. Therefore, we briefly described the process of autophagy, emphasizing its function in different cell types involved in bone development and metabolism (including bone marrow mesenchymal stem cells, osteoblasts, osteocytes, chondrocytes, and osteoclasts), and also summarized research advances in natural product-mediated autophagy for the treatment of metabolic bone disease caused by dysfunction of these cells (including osteoporosis, rheumatoid joints, osteoarthritis, fracture nonunion/delayed union). The objective of the study was to identify the function that autophagy serves in metabolic bone disease and the effects, potential, and challenges of natural products for the treatment of these diseases by targeting autophagy.

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration.

Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.

Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Promotes Forelimb Functional Recovery after Cervical Spinal Cord Injury.

Locomotor function after spinal cord injury (SCI) is critical for assessing recovery. Currently, available means to improve locomotor function include surgery, physical therapy rehabilitation and exoskeleton. Stem cell therapy with neural progenitor cells (NPCs) transplantation is a promising reparative strategy. Along this line, patient-specific induced pluripotent stem cells (iPSCs) are a remarkable autologous cell source, which offer many advantages including: great potential to generate isografts avoiding immunosuppression; the availability of a variety of somatic cells without ethical controversy related to embryo use; and vast differentiation. In this current work, to realize the therapeutic potential of iPSC-NPCs for the treatment of SCI, we transplanted purified iPSCs-derived NPCs into a cervical contusion SCI rat model. Our results showed that the iPSC-NPCs were able to survive and differentiate into both neurons and astrocytes and, importantly, improve forelimb locomotor function as assessed by the grooming task and horizontal ladder test. Purified iPSC-NPCs represent a promising cell type that could be further tested and developed into a clinically useful cell source for targeted cell therapy for cervical SCI patients.

Effect of Rhizoma Drynariae on differential gene expression in ovariectomized rats with osteoporosis based on transcriptome sequencing.

Osteoporosis is increasingly becoming a serious problem affecting the quality of life of the older population. Several experimental studies have shown that Chinese medicine has a definite effect on improving osteoporosis. Based on transcriptome sequencing, we analyzed the differential gene expression and mechanism of the related signaling pathways. Fifteen rats were randomly divided into an experimental group, a model group, and a sham surgery group. The rat model for menopausal osteoporosis was established using an ovariectomy method. One week after modeling, the experimental group was administered(intragastric administration)8.1 g/kg of Rhizoma drynariae, whereas the model and sham groups received 0.9% saline solution twice daily for 12 weeks. Subsequently, the rats were sacrificed, and the left femur of each group was removed for computerized tomography testing, while right femurs were used for hematoxylin and eosin staining. High-throughput RNA sequencing and functional and pathway enrichment analyses were performed. Comparing the gene expression between the experimental and model groups, 149 differential genes were identified, of which 44 were downregulated and 105 were upregulated. The criteria for statistical significance were |log2 Fold Change| > 1 and P < 0.05. Gene ontology analysis showed that the differentially expressed genes were enriched in cell component terms such as cell part and outer cell membrane part, and the genes were associated with cell process, biological regulation, metabolic processes, DNA transcription, and catalytic activity. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed significantly enriched pathways associated with systemic lupus erythematosus, herpes simplex infection, circadian rhythm, vascular smooth muscle contraction, the AGE-RAGE signaling pathway in diabetic complications, and the TNF, Apelin, and Ras signaling pathways. Our results revealed that the Npas2, Dbp, Rt1, Arntl, Grem2, H2bc9, LOC501233, Pla2g2c, Hpgd, Pde6c, and Dner genes, and the circadian rhythm, lipid metabolism, inflammatory signaling pathway, and immune pathways may be the key targets and pathways for traditional Chinese medicine therapy of Rhizoma Drynariae in osteoporosis.

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review).

Osteoporosis is a common metabolic bone disorder typically characterized by decreased bone mass and an increased risk of fracture. At present, the detailed molecular mechanism underlying the development of osteoporosis remains to be elucidated. Accumulating evidence shows that non­coding (nc)RNAs, such as microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), play significant roles in osteoporosis through the post­transcriptional regulation of gene expression as regulatory factors. Previous studies have demonstrated that ncRNAs participate in maintaining bone homeostasis by regulating physiological and developmental processes in osteoblasts, osteoclasts and bone marrow stromal cells. In the present review, the latest research investigating the involvement of miRNAs, lncRNAs and circRNAs in regulating the differentiation, proliferation, apoptosis and autophagy of cells that maintain the bone microenvironment in osteoporosis is summarized. Deeper insight into the aspects of osteoporosis pathogenesis involving the deregulation of ncRNAs could facilitate the development of therapeutic approaches for osteoporosis.

Clinical Observations of Kümmell Disease Treatment Through Percutaneous Fixation Combined with Vertebroplasty.

OBJECTIVE: To explore the safety and efficacy of percutaneous pedicle screw fixation combined with vertebroplasty for the treatment of stage III Kümmell disease. METHODS: The clinical data and follow-up results of 22 patients with Kümmell disease who were admitted to our department from 2014 to 2018 were analyzed. There were 14 females and eight males, and the Age range was 58-81 years. All patients were followed up for 24 months. The treatment method was percutaneous pedicle screw fixation combined with vertebroplasty. The patient general information such as age, gender, bedrest time and location of fracture vertebrae were recorded. The clinical symptoms and imaging data of visual analogue scale (VAS), bone cement leakage, Oswestry Disability Index (ODI), Cobb angle, anterior, middle and posterior height of the diseased vertebral body, and complications were recorded before operation and during follow-up. RESULTS: For patients enrolled, no bone cement leakage was observed during the operation; no patients developed infections after operation. The operation was safe and resulted in a short bedrest time. The VAS score and ODI index at 3 and 24 months postoperative (2.86 ± 0.83, 31.68% ± 6.21%; 3.0 ± 0.82, 32.78% ± 6.05%) were significantly lower than that recoded preoperatively (7.59 ± 0.59, 71.5% ± 8.84%) (P < 0.05). Additionally, there was no significant difference between the records at 3 and 24 months after operation (P > 0.05). Imaging data showed that the bone cement and screws were in good position and did not move during postoperative and follow-up. The anterior, middle and posterior height of the diseased vertebral body measured 2 days after surgery (23.46 ± 4.72, 23.12 ± 3.05, 25.81 ± 2.22) and at last follow-up (20.83 ± 4.48, 21.78 ± 2.74, 24.74 ± 1.93) were higher than that recorded preoperatively (13.08 ± 4.49, 12.93 ± 3.53, 19.32 ± 2.73) (P < 0.05), and the Cobb angle measured 2 days and 24 months after operation (9.57 ± 4.63, 10.68 ± 3.97) were lower than that recorded preoperatively (28.24 ± 8.95) (P < 0.05), and no significant difference was found between the values recorded at 2 days and 24 months after operation (P > 0.05). Follow-up for 24 months, there was no re-fracture of the diseased vertebrae and internal fixation loosening, but two cases of adjacent vertebral refracture complications occurred, and the effect was good after PVP treatment. CONCLUSION: Short-segment percutaneous pedicle screw fixation combined with vertebroplasty in the treatment of stage III Kümmel disease can effectively restore the height of the diseased vertebrae, kyphosis correction, reduce trauma, prevent the diseased vertebral body from collapsing again, and effectively improves clinical symptoms.

Application of enhanced recovery after surgery in total knee arthroplasty in patients with haemophilia A: A pilot study.

Aim: To identify the effect of enhanced recovery after surgery (ERAS) and rapid rehabilitation concepts on the outcomes of patients with haemophilia A undergoing total knee arthroplasty. Design: Randomized controlled trial. Methods: The primary endpoint was postoperative hospital stay. The secondary endpoints were pain scores, joint function scores, haemoglobin levels at 3 and 7 days after surgery and satisfaction with hospitalization. Results: Thirty-two patients were enrolled. Compared with the routine nursing group, the ERAS group showed shorter postoperative hospital stay (14.2 SD 0.8 vs. 16.6 ± 1.3 days, p < .001), smaller amounts of blood transfusion (924 SD 317 vs. 1,263 SD 449 ml, p = .020) and coagulation factors (37,325 SD 5,996 vs. 48,475 SD 8,019 U, p < .001), lower pain scores at 3 (3.3 SD 0.7 vs. 4.3 SD 0.7, p = .002) and 7 (2.3 SD 0.7 vs. 2.8 ± 0.5, p = .015) days, lower hospital for special surgery knee scores at 3 (59.9 SD 7.8 vs. 53.6 SD 5.9, p = .016) and 7 (77.9 SD 6.9 vs. 71.1 ± 7.1, p = .009) days and higher satisfaction with hospitalization (94.3 SD 1.4 vs. 92.7 SD 1.6, p = .004).

Combined use of tranexamic acid and rivaroxaban in posterior lumbar interbody fusion safely reduces blood loss and transfusion rates without increasing the risk of thrombosis-a prospective, stratified, randomized, controlled trial.

PURPOSE: This prospective, stratified, randomized, single-blind, placebo-controlled multicentre study investigated the safety and effectiveness of reducing blood loss and preventing venous thromboembolism (VTE) during posterior lumbar interbody fusion (PLIF) in patients with stenosis or spondylolisthesis using the combination of tranexamic acid (TXA) and rivaroxaban. METHODS: The Autar score was evaluated in patients after admission. Patients with an Autar score ≤ 10 were randomized to group A or B. Group A was the placebo-controlled group. Patients in group B were treated with 1 g TXA via intravenous injection and 1 g TXA for external use. Patients with an Autar score > 10 were randomized to group C or D. Patients in group C were treated with 10-mg rivaroxaban qd for 35 days after surgery. Patients in group D received the same treatment as those in group B intra-operatively and as those in group C post-operatively. RESULTS: A total of 599 patients from eight hospitals participated in this clinical trial. The total blood loss, intra-operative blood loss, and drainage volume were reduced by the administration of TXA (group A vs group B, P < 0.01; group C vs group D, P < 0.01), and the blood transfusion rate was also decreased (group A vs group B, P < 0.01; group C vs group D, P < 0.01). There were no significant differences (P > 0.05) in the VTE incidence rates among group A and group B. In patients with high-risk thrombosis, the number of patients with VTE was only three and seven after the application of rivaroxaban. Epidural haematoma was not discovered in any patients in our trial. CONCLUSION: The combined application of tranexamic acid and rivaroxaban significantly reduced the amount of blood loss and the transfusion rate during PLIF surgery and avoided an increase in the probability of thrombosis and the occurrence of epidural haematoma. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ChiCTR-1800016430 2018-06-01.

Author Correction: Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome.

Down syndrome (DS) is a common neurodevelopmental disorder, and cognitive defects in DS patients may arise from imbalances in excitatory and inhibitory neurotransmission. Understanding the mechanisms underlying such imbalances may provide opportunities for therapeutic intervention. Here, we show that human induced pluripotent stem cells (hiPSCs) derived from DS patients overproduce OLIG2+ ventral forebrain neural progenitors. As a result, DS hiPSC-derived cerebral organoids excessively produce specific subclasses of GABAergic interneurons and cause impaired recognition memory in neuronal chimeric mice. Increased OLIG2 expression in DS cells directly upregulates interneuron lineage-determining transcription factors. shRNA-mediated knockdown of OLIG2 largely reverses abnormal gene expression in early-stage DS neural progenitors, reduces interneuron production in DS organoids and chimeric mouse brains, and improves behavioral deficits in DS chimeric mice. Thus, altered OLIG2 expression may underlie neurodevelopmental abnormalities and cognitive defects in DS patients.

[Clinical outcomes of buttress plating in treating posterior Pilon fractures through modified posteromedial approach].

OBJECTIVE: To explore clinical outcomes of buttress plating in treating posterior Pilon fracture by amodified posteromedial approach. METHODS: From July 2014 to January 2015, 10 patients with posterior Pilon fracture were respectively analyzed, including 7 females and 3 males, aged from 31 to 54 years old. One patient were type , 3 patients were type IIand 6 patients were type III according to classification of Pilon fracture by YU Guang-rong. All patients were treated by buttress plating through amodified posteromedial approach. Postoperative complications, fracture healing and reduction were observed, AOFAS score were used to evaluate function recovery at 1 year after operation. RESULTS: All patients were followed up for 12 to 18 months with an average of(14.1±3.2) months. All incisions were primarily healed at stage I without wound complication, neurovascular injuries or musculus flexor contracture. According to Burwell-Charnley imaging scoring, 8 patients got anatomical reduction and 2 patients got moderate reduction. All fracture got healing from 12 to 16 weeks with an average of(13.2±1.8) weeks. According to AOFAS score at 1 year after operation, 8 got excellent results and 2 moderate. All patients returned to work at about(4.7±1.4) months (ranged from 3 to 6 months) after operation. CONCLUSIONS: Buttress plating using a modified posteromedial approach in treating posterior Pilon fractures is an effective method, has less complications, and could recovery early weight-bearing functional exercise.