BACKGROUND:Black phosphorus has a high degree of homology with human bone,so it has been extensively studied in the field of bone tissue engineering in recent years.Since 2014,two-dimensional black phosphorus materials have garned significant attention in the field of biomedicine due to their excellent exceptional physical,chemical,and biological properties. OBJECTIVE:To summarize the advancements made in black phosphorus-based nanomaterials for bone tissue engineering,focus on the synthesis methods,osteogenic characteristics,and applications in biomaterials pertaining to two-dimensional black phosphorus nanomaterials. METHODS:Chinese and English key words were"black phosphorus,bone tissue engineering,bone defect,bone regeneration,osteogenesis."Relevant articles in PubMed and CNKI databases from January 2014 to December 2023 were searched.After exclusion and screening,96 articles were analyzed. RESULTS AND CONCLUSION:Black phosphorus nanomaterials play an important role in bone tissue engineering due to their good biocompatibility,biodegradability,photothermal action,antibacterial ability,drug loading performance,and special osteogenic effect,and are ideal candidate materials for promoting bone regeneration.The preparation of black phosphorus nanomaterials is mainly a top-down top-layer stripping method.The main principle is to weaken the van der Waals force between the black phosphorus layers by physical or chemical means to obtain a single or less layer of phosphanse,that is,black phosphorus nanosheets or quantum dots.Black phosphate-based nanocomposites are mainly divided into hydrogels,3D printing scaffolds,composite scaffolds,electrospinning,bionic periosteum,microspheres,and bionic coatings.The research of nano-black phosphorus in bone tissue engineering is in its infancy,and still faces many challenges:the behavior of black phosphorus in vivo and the interaction mechanism with various biomolecules need to be further studied.The long-term potential toxicity of black phosphorus is unknown.The manufacturing process for black phosphorus is difficult to control.Therefore,how to develop uniform size,safe,reliable,and efficient nano black phosphorus and transform it into clinical application requires interdisciplinary research on modern biomedical technology,physicochemical technology,and precision manufacturing technology.

Lumbosacral radiculopathy refers to the pain syndrome caused by inflammation or mechanical compression of the lumbar nerve root, mainly manifested as low back pain, and radiating to the lower limbs in cutaneous mode, which can be accompanied by numbness, paresthesia, tingling, muscle weakness and loss of specific reflexes and other symptoms, which not only bring physical pain and life inconvenience to the patients, but also bring huge economic burden to the social medical care. Selective nerve root block(SNRB), as a safe, effective, low-cost, precise and minimally invasive clinical technique, can accurately intervene in specific nerve roots and quickly relieve pain symptoms by reducing inflammation and improving the surrounding environment of nerves. However, there are still many challenges and controversies in practice, such as precise targeting requirements, drug selection, potential risks and complications, and differences in efficacy among different patient populations. The purpose of this review is to systematically review and analyze the existing research results on SNRB, so as to provide useful reference and guidance for the further development of this field.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

BACKGROUND:In the treatment strategy of chronic osteomyelitis,the local antibiotic slow-release system has attracted much attention in the clinic due to the long-term release of effective concentrations of antibiotics to control the infection,and at the same time,the ability to repair bone defects caused by debridement. OBJECTIVE:To summarize the research status of antibiotic sustained-release carriers prepared from biodegradable polymer-based materials for the treatment of osteomyelitis,and analyze the limitations and challenges. METHODS:Chinese and English key words were"polymer,composite material,osteomyelitis,infectious bone defect,drug delivery systems,antibiotic sustained-release system,3D printing".Relevant articles were searched in PubMed,Web of Science,CNKI,and WanFang databases from January 2015 to August 2023.4 351 articles were obtained in the initial examination,and 87 articles were analyzed after screening. RESULTS AND CONCLUSION:Polymer-based materials have been widely studied in the preparation of antibiotic sustained-release carriers due to their good biocompatibility,biodegradability,thermal stability,and easy processing.However,the antibiotic slow-release carrier composed of a single polymer material cannot meet the standard of infectious bone defect repair materials due to the lack of biomechanical properties.The organic-inorganic composite material carrier,which simulates the formation of natural bone tissue structure,is expected to meet this standard.3D printing technology can precisely control the size,geometry,and spatial distribution of the interconnecting pores of the carrier,and can load the effective concentration of antibiotics to achieve controlled release.The polymer material is the most suitable for 3D printing because of its good thermal stability and plasticity.Therefore,the author believes that on the basis of new biodegradable organic-inorganic composite materials and combined with 3D printing technology,the material-structure-function integrated composite antibiotic slow-release carrier to simulate the extracellular matrix microenvironment is expected to become a novel research direction in the treatment of chronic osteomyelitis.

BACKGROUND:In the past,it was necessary to cut off the pronator quadratus muscle in the treatment of distal radius fractures.Failure to repair the pronator quadratus muscle can lead to a series of complications. OBJECTIVE:To explore the clinical efficacy of different methods of preserving the pronator quadratus muscle combined with a palmar steel plate in the treatment of distal radius fractures. METHODS:Clinical data of 66 patients with distal radius fractures were retrospectively included,divided into the traditional Henry approach group(group A),the split brachioradialis tendon approach group(group B),and the posterior pronator quadratus muscle approach group(group C),with 22 patients in each group.Postoperative internal fixation,fracture healing,and postoperative complications were observed in the three groups.The visual analog scale score of postoperative wrist pain and forearm rotation angle were compared among the three groups.The Dienst Joint Scale was used to evaluate the wrist function of patients. RESULTS AND CONCLUSION:(1)The surgical time,intraoperative blood loss,and fracture healing time of groups B and C were significantly lower than those of group A(P<0.01).There was no significant difference in intraoperative blood loss and fracture healing time between groups B and C,but the surgical time was shorter in group B.(2)The anteroposterior and lateral wrist X-ray examination 3 days and 1 and 3 months after surgery exhibited that there were no significant differences in radial height,palm angle,and ulnar deviation angle among the three groups(P>0.05).No significant difference was detected in various indicators during the same phase among the three groups(P>0.05).(3)At a follow-up of 12 months after surgery,there were no significant differences in visual analog scale scores and forearm rotation angle among the three groups.However,the evaluation results at 1 and 3 months after surgery demonstrated significant differences in visual analog scale scores and forearm rotation angle among the three groups(P<0.05).Among them,group C had a lower visual analog scale score and a larger forearm rotation angle.(4)According to the Dienst joint scoring standard,the excellent and good rate of wrist joint function evaluation was 86%(19/22),91%(20/22),and 95%(21/22)in groups A,B,and C,respectively 12 months after surgery.(5)All patients did not experience any postoperative vascular or neurological damage or surgical site infection.Group A had three cases of tendon irritation,two cases of traumatic arthritis,and two cases of carpal tunnel syndrome.In group B,tendon irritation occurred in 1 case and joint stiffness in 1 case.There was 1 case of traumatic arthritis and 1 case of carpal tunnel syndrome in group C.(6)It is suggested that different surgical methods for treating distal radius fractures have achieved good clinical results.Placing a steel plate under the pronator muscle can alleviate early postoperative pain,promote early activity,and restore normal life.The brachioradialis tendon approach has more advantages in exposing intraoperative fractures and can shorten the surgical time.

BACKGROUND:Yougui Pill is a famous formula of the Chinese traditional medicine,which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE:To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology,and verified by animal experiments. METHODS:(1)Network pharmacological analysis:We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases,collected genes related to lumbar disc herniation from GeneCards database,and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets.Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software.(2)Molecular docking:Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets.(3)Animal experiments:Eighteen Sprague-Dawley rats were randomly divided into a control group,a degeneration group and a Yougui Pill group,with 6 rats in each group.A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups.At 2 weeks after modeling,Yougui Pill was given by gavage in the Yougui Pill group,once a day for 2 consecutive weeks.The level of tumor necrosis factor-α in serum was detected by the ELISA method,and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION:There were 90 active ingredients and 64 targets,and the main active ingredients were found to be quercetin,kaempferol,β-carotene,soybean flavonoid,and 4'-O-methylnyasol.The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6,tumor necrosis factor-α,AKT1,interleukin 1B,and vascular endothelial growth factor A.Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,and other signaling pathways to improve intervertebral disc degeneration.The molecular docking test verified that quercetin,kaempferol,and β-carotene had strong binding ability to the core targets.Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group(P<0.05),and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group(P<0.05).Hematoxylin-eosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed,and the number of nucleus pulposus cells was reduced;there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group,and the number of nucleus pulposus cells increased compared with the degeneration group.To conclude,Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin,kaempferol,beta-carotene and other key active ingredients on core targets such as tumor necrosis factor.

This paper aims to review treatment delay in first-episode schizophrenia,depression,and bipolar disorder,and to compare related factors of treatment delay in the three first-episode mental disorders.It is found that increased patient responsibility,stigma,lack of disease-related knowledge,lack of access to resources,and insuffi-cient medical support lead to delay treatment,and making patients to have longer course,heavier symptoms,and lower social functions.