Steroid inhibited Serpina3n expression which was positively correlated with the degrees of spinal cord injury.

Aims: The aim of our project was to identify proteins associated with the extent of spinal cord injury (SCI) and subsequent long-term neurological recovery. Methods: Through proteomic analysis, we identified proteins that are differentially expressed specifically in the acute phase of injury. We analyzed the concentrations of differentially expressed proteins in serum and the injured spinal cord segment by ELISA. Results: Serpina3n protein expression in the injured spinal cord segment was increased 101-fold at 12 h after severe SCI and 89-fold at 12 h after mild SCI, as determined by LC‒MS/MS. In the mild and severe SCI groups, serum Serpina3n levels began to increase at 12 h and peaked at 24 h. At 12 h, 24 h and 3 d after injury, serum Serpina3n protein levels were significantly correlated with the severity of injury (12 h: r = 0.6034, P = 0.008; 24 h: r = 0.7542, P = 0.0003; 3 d: r = 0.862, P < 0.001). Serum Serpina3n levels at 2 h, 24 h and 3 d post injury were significantly correlated with long-term neurological recovery at 28 d after SCI (2 h: r = -0.5781, P = 0.012; 24 h: r = -0.5912, P = 0.0098; 3 d: r = -0.7792, P < 0.0001). Methylprednisolone treatment would decrease the serum Serpina3n levels in mice with mild and severe SCI compared with those in placebo-group mice at 12 h and 24 h after SCI. The serum Serpina3n concentration in the severe SCI group was significantly reduced on the third day after steroid treatment. Conclusion: Taken together, these data suggest that serpina3n may be a circulating biomarker of acute SCI and may be closely associated with injury severity and long-term motor function recovery.

The use of high-resolution SNP arrays to detect congenital cardiac defects.

OBJECTIVE: Copy number variations (CNVs) detected by high-resolution single nucleotide polymorphism microarrays (SNP arrays) have been associated with congenital heart defects (CHDs). The genetic mechanism underlying the development of CHDs remains unclear. METHODS: High-resolution SNP arrays were used to detect CNVs and traditional chromosomal analyses, respectively, were carried out on 60 and 249 fetuses from gestational 12-37 weeks old, having isolated or complex CHDs that were diagnosed using prenatal ultrasound. RESULTS: Twenty of the 60 fetuses (33.5%) had abnormalities, of which 23 CNVs (12 pathogenic, five probable pathogenic and six of undetermined significance) were detected by SNP arrays, and two distinct CNVs were present in three of these fetuses. In addition, in 39 patients with isolated congenital heart disease who had normal karyotypes, abnormal CNVs were present in 28.2% (11/39), and in patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. In patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. CONCLUSIONS: In conclusion, genome-wide high-resolution SNP array can improve the diagnostic rate and uncover additional pathogenic CNVs. The submicroscopic deletions and duplications of Online Mendelian Inheritance in Man (OMIM) genes found in this study have haploinsufficient (deletion) or triplosensitive (duplication) traits, which further clarify the etiology and inheritance of CHDs.

Tendon Repair and Regeneration Using Bioinspired Fibrillation Engineering That Mimicked the Structure and Mechanics of Natural Tissue.

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.

Dynamic changes of oligodendrogenesis in neonatal rats with hypoxic-ischemic white matter injury.

BACKGROUND: White matter injury (WMI) is an important type of preterm brain injury, which may result in severe neurological sequelae and lack of effective treatments. It is ascertained that selective vulnerability of oligodendrocytes is closely related to the WMI in preterm infants. But the alteration of the endogenous oligodendrogenesis over long time after hypoxic-ischemic WMI is still not clearly elucidated. METHODS: We adopted an animal model of hypoxic-ischemic WMI in 3-day-old neonatal Sprague-Dawley rats. Immunofluorescence staining and western blotting were used to detect dynamic changes of oligodendrogenesis in the white matter region on postoperative day (POD) 1, 3, 7, 14, 28, 56 and 84. RESULTS: In the sham group, the oligodendrocyte lineage in the white matter reached a developmental peak from POD 3 to 14. The proliferation and development of oligodendrocyte precursor cells (OPCs) occurred primarily within POD 14. The number of mature oligodendrocytes showed an upward trend and a dynamic change in proliferation over time. While in the WMI group, the oligodendrocyte lineage was upregulated on POD1 and 3 but downregulated on POD 7 and 14. The proliferation of OPCs increased on POD 1 and decreased on POD 3 and 7, with the total number of OPCs significantly reduced from POD 3 to 14. The number of mature oligodendrocytes decreased from POD 3 to 28, and return to the level of the sham group on POD 56 and 84, whereas the MBP expression was still significantly downregulated on POD 56 and 84. CONCLUSIONS: Hypoxia-ischemia can have a long-term dynamic effect on the endogenous oligodendrogenesis of neonatal rat brain white matter. The proliferation of OPCs was promoted on POD 1 but inhibited from POD 3 to 14, which may be an early intervention target to improve oligodendrogenesis. The number of mature oligodendrocytes recover to the normal on POD 56 and 84 but the myelination is still blocked, which suggests it is essential to promote the maturation of oligodendrocyte and its function recovery at the same time within POD 28. Such efforts will provide the opportunity to test new interventions in pre-clinical studies for their promising clinical application.

Effect of Hypoxia-Ischemia on the Expression of Iron-Related Proteins in Neonatal Rat Brains.

Hypoxic-ischemic white matter injury (WMI) pathogenesis in preterm infants is not well established, and iron-related proteins in the brain may play an important role in imbalanced iron metabolism. We aimed to investigate the iron-related protein changes in neonatal rats after hypoxia-ischemia (HI), clarify the role of iron-related proteins in hypoxic-ischemic WMI, and potentially provide a new target for the clinical treatment of hypoxic-ischemic WMI in preterm infants. We adopted a WMI animal model of bilateral common carotid artery electrocoagulation combined with hypoxia in neonatal 3-day-old Sprague-Dawley rats. We observed basic myelin protein (MBP) and iron-related protein expression in the brain (ferritin, transferrin receptor [TfR], and membrane iron transporter 1 [FPN1]) via Western blot and double immunofluorescence staining. The expression of MBP in the WMI group was significantly downregulated on postoperative days (PODs) 14, 28, and 56. Ferritin levels were significantly increased on PODs 3, 7, 14, and 28 and were most significant on POD 28, returning to the sham group level on POD 56. FPN1 levels were significantly increased on PODs 7, 28, and 56 and were still higher than those in the sham group on POD 56. TfR expression was significantly upregulated on PODs 1, 7, and 28 and returned to the sham group level on POD 56. Immunofluorescence staining showed that ferritin, TfR, and FPN1 were expressed in neurons, blood vessels, and oligodendrocytes in the cortex and corpus callosum on POD 28. Compared with the sham group, the immune-positive markers of three proteins in the WMI group were significantly increased. The expression of iron-related proteins in the brain (ferritin, FPN1, and TfR) showed spatiotemporal dynamic changes and may play an important role in hypoxic-ischemic WMI.

Precise manipulation of circadian clock using MnO2 nanocapsules to amplify photodynamic therapy for osteosarcoma.

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 MnO2 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.

Chronic intermittent hypoxia impaired collagen synthesis in mouse genioglossus via ROS accumulation: A transcriptomic analysis.

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by intermittent and recurrent upper airway collapse during sleep that leads to chronic intermittent hypoxia (CIH). The genioglossus (GG) is the largest dilator muscle, which controls the upper airway and plays an important role in OSA pathology. Elucidating its genetic alterations may help identify potential targets for OSA. However, the genetic aspects of the GG in CIH mice remain unclear. Here, we have conducted an RNA sequencing (RNA-Seq) analysis to assess the differentially expressed genes (DEGs) in the GG between CIH mice and normoxia (NOR) mice. A total of 637 DEGs were identified to be dysregulated in CIH mice compared with control mice. Bioinformatics analysis showed that the DEGs were related to various physiological processes, such as the endogenous stimulus responses, cellular component organization and metabolic processes. Extracellular matrix (ECM)-receptor interaction was the top KEGG pathway in the environmental information processing category with high significance and large fold changes. From the gene weight distributions of collagen (Col)-related biological processes (BPs), we found several significant DEGs, such as Col1a1, Col1a2, Mmp2, Col3a1, Col5a1, Fmod, and Col5a2. A PPI network showed that Col1a1 was linked to ECM-receptor interactions, responses to reactive oxygen species (ROS) and Col-related BPs. It was verified in vivo and in vitro that hypoxia can induce excess ROS and reduce Col expression levels. Moreover, we found NAC can effectively scavenge ROS and restore collagen synthesis. These findings contribute to a better understanding of the mechanisms linking OSA and upper airway muscle injury and may help identify potential therapeutic targets.

Piezoresistive MXene/Silk fibroin nanocomposite hydrogel for accelerating bone regeneration by Re-establishing electrical microenvironment.

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 ß-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 Ca2+/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.

Systematic evaluation of the incidence of the knee donor area after autobone cartilage mosaic xentoplasty / 中国骨伤

OBJECTIVE@#To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty.@*METHODS@#A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed.@*RESULTS@#A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7).@*CONCLUSION@#Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

Related factors of abnormal body posture among urban primary school students in Yinchuan / 中国学校卫生

Objective@#To investigate the incidence and influencing factors of abnormal body posture among urban primary school students in Yinchuan City, and to provide evidence for the prevention and treatment of abnormal body posture.@*Methods@#A multi stage stratified cluster random sampling method was adopted to select 1 947 urban primary school students aged 7-12 years from 9 schools in Yinchuan City. Body Style(Model.S-8.0) instrument was used to screen abnormal body posture and questionnaire was designed to investigate related factors.@*Results@#The comprehensive body posture score of urban primary school students in Yinchuan City was(22.07±2.87), and the detection rate of abnormal posturing was 71.29%；which varied significantly by gender, age, body mass index (BMI)( χ 2=9.84, 13.47, 6.46, P <0.05). Specially, the rate of girls (73.54%) was higher than that of boys( 69.07 %); the abnormal rate of children aged 7-8(68.24%) was lower than that of 9-10(72.17%) and 11-12(73.54%); obese children (74.91%) was higher than that of overweight (72.64%) and normal weight children(70.28%). The high and low shoulders (40.73%), pelvis forward (39.39%) and X/O legs (38.57%) were the most common indicators of abnormal posture; the composition of the overall body posture abnormalities was higher in mild (54.32%) than moderate (37.82%) and severe (7.85%).Multivariate Logistic regression analysis showed that girls( OR =1.23), being older(9-10 years old OR =1.89, 11-12 years old OR = 2.48 ), overweight ( OR =1.39) and obesity( OR =2.34), occasionally participate in physical exercise ( OR =2.96), exercise duration <30 minutes daily ( OR =2.77), video duration ≥2 h daily ( OR =2.84), almost no dairy products ( OR =1.79), almost no food Fish consumption ( OR =1.77), almost no vegetables ( OR =2.14), drinking carbonated beverages daily ( OR =2.97), and sleeping time <6 h daily ( OR =2.56) were the related factors of body posture development of urban primary school students( P <0.05).@*Conclusion@#The abnormal body posture of urban primary school students in Yinchuan City is prevalent, which is related to the timely length of physical exercise, nutrition, video screen and sleep duration, and should be paid enough attention.

Physical activity of middle school students in January 2023 in Ningxia / 中国学校卫生

Objective@#To investigate physical activity status and associated factors of middle school students in Ningxia in January 2023, and to provide references for the better development of physical activity among middle school students.@*Methods@#In February 1-7,2023, a convenient sampling method was used to select 6 593 middle school students in 5 prefectural cities of Ningxia. Online questionnaires were used to investigate physical activity and its influencing factors in the previous month.@*Results@#The detection rates of sedentary behavior, light physical activity, moderate physical activity and vigorous physical activity was 92.25%, 4.66%, 2.72% and 0.38%, respectively. Multivariate Logistic regression analysis showed that being female, older age, overweight, obesity, COVID-19 infection, low to moderate family support, low to moderate level knowledge of physical activity, insufficient physical activity skills, insufficient physical activity equipment, long distance (>2.5 km or above) were associated with less physical activity ( OR=1.22, 2.47, 1.89, 1.39, 2.32, 1.20, 2.61, 1.85, 1.45, 1.23, 1.26, 1.11, 2.05, 1.77, 1.14, 1.43, P <0.05).@*Conclusion@#The poor physical activity performance of middle school students in Ningxia is related to BMI, COVID-19 infection, physical activity knowledge and skills, distance from activity places, etc. The influencing factors should be actively controlled to promote students physical health.

Mechanochemically synthesized zeolitic imidazolate framework-8 as sorbent for dispersive solid-phase extraction of benzophenone-type ultraviolet filters in aqueous samples.

Benzophenone-type ultraviolet filters (BP-UVFs) are a group of emerging contaminants, which found in various environmental aqueous samples raising potential risks for public health concern and could bioaccumulate in the food chain. This study describes a simple and "green" method to rapidly analyze five BP-UVFs that are frequently found in surface water and in seawater samples. Dispersive solid-phase extraction (DSPE) using a zeolitic imidazolate framework­8 (ZIF-8) as the sorbent was applied to efficiently extract the BP-UVFs from aqueous samples, and they were then detected and quantified by UHPLC-electrospray ionization (+)-quadrupole time-of-flight mass spectrometry (UHPLC-ESI (+)-QTOF-MS). The ZIF-8 sorbent was synthesized by a green one-step mechanochemical process using water-assisted grinding and a stoichiometric reaction. The Box-Behnken Design coupled with the response surface method was applied to optimize the main DSPE extraction factors. The developed method was fully validated, showing low limits of quantification (LOQs; 0.3-20 ng L-1), satisfactory mean spiked recoveries (72-105%), and a high level of precision (3-9%). A preliminary analysis of the surface water and seawater samples revealed that 2-hydroxy-4-methoxybenzophenone (BP-3) was the most common BP-UVF present in our aquatic environment, likely due to its widespread applications and slow rate of degradation.

Precisely Targeted Nano-Controller of PD-L1 Level for Non-Small Cell Lung Cancer Spinal Metastasis Immunotherapy.

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin ß3 (ß3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles (ZnPP@MSN-RGDyK) are fabricated. The ZnPP@MSN-RGDyK nanoparticles precisely target ß3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that ZnPP@MSN-RGDyK is a promising immunotherapeutic agent for treating NSCLC-SM.

Siglec15 Checkpoint Blockade for Simultaneous Immunochemotherapy and Osteolysis Inhibition in Lung Adenocarcinoma Spinal Metastasis via a Hollow Nanoplatform.

Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp8 ), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp8 exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.

Multidata Analysis Based on an Artificial Neural Network Model for Long-Term Pain Outcome and Key Predictors of Microvascular Decompression in Trigeminal Neuralgia.

OBJECTIVE: To investigate use of multidata analysis based on an artificial neural network (ANN) to predict long-term pain outcomes after microvascular decompression (MVD) in patients with trigeminal neuralgia (TN) and to explore key predictors. METHODS: Perioperative and long-term follow-up multidata of 1041 patients with TN who received MVD surgery at Hangzhou First People's Hospital from March 2013 to May 2018 were collected to construct an ANN model for prediction. The prediction results were compared with the actual follow-up outcomes, and the variables in each input layer were changed to test the effectiveness of ANN and explore the factors that had the greatest impact on prediction accuracy. RESULTS: The ANN model could predict the long-term pain outcomes after MVD in patients with TN with an accuracy rate of 95.2% and area under the curve of 0.862. Four factors contributed the most to the predictive performance of the ANN: whether the neurovascular offending site of the trigeminal nerve corresponded the region of facial pain, immediate postoperative pain remission after MVD, degree of nerve compression by culprit vessels, and the type of culprit vessels. After these factors were sequentially removed, the accuracy of the ANN model decreased to 74.5%, 78.6%, 87.2%, and 90.1%, while the area under the curve was 0.705, 0.761, 0.793, and 0.810. CONCLUSIONS: The ANN model, constructed using multiple data, predicted long-term pain prognosis after MVD in patients with TN objectively and accurately. The model was able to assess the importance of each factor in the prediction of pain outcome.

Siglec15 facilitates the progression of non-small cell lung cancer and is correlated with spinal metastasis.

Background: Non-small cell lung cancer (NSCLC) frequently metastasizes to bone, leading to poor prognosis. Siglec15 has been identified as a newly discovered immune checkpoint and exists in a variety of tumors. However, the expression and function of Siglec15 in NSCLC and bone metastasis remains largely unclear. Methods: Siglec15 expression in NSCLC and the correlation between Siglec15 expression and the clinicopathological factors of patients with NSCLC were analyzed using The Cancer Genome Atlas (TCGA) dataset. Correlation analysis between Siglec15 and bone metastasis-related genes expression was based on the Molecular Signatures Database (MSigDB). Western blotting and immunohistochemistry were applied to detect Siglec15 expression in NSCLC and spinal metastasis. Human A549 and mouse CMT167 cells were transfected with Siglec15 siRNA to investigate its biological functions in NSCLC proliferation, migration, and invasion. The immune-related signaling pathways and correlations between Siglec15 and tumor-infiltrating immune cells and different immune checkpoints in the NSCLC tumor microenvironment (TME) were analyzed using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and gene set enrichment analysis (GSEA). To demonstrate Siglec15 in NSCLC cell-mediated T cell suppression and investigate the potential mechanism of Siglec15 silencing in antitumor immunity, we used a T cell killing assay in vitro and the high­throughput sequencing approach. Results: Siglec15 expression was positively associated with the tumor stage and lymph node metastasis, and was markedly up-regulated in NSCLC bone metastasis. Functionally, Siglec15 knockdown inhibited the proliferation, migration, and invasion of NSCLC cells (A549 and CMT167 cell lines). A total of eight kinds of tumor-infiltrating immune cells were found to have a strong association with the Siglec15 expression in NSCLC cases. The expression of previously discovered immune checkpoints was higher in the high Siglec15 expression NSCLC group. Furthermore, an in vitro T cell killing assay showed that the down-regulation of Siglec15 in tumor cells could enhance the antitumor immune responses of CD8+ T cells. High­throughput sequencing revealed the potential molecular mechanisms underlying the Siglec15-mediated immunosuppression effect of tumor cells on immune cells. Conclusions: Siglec15 may be involved in the pathogenesis of spinal metastasis in NSCLC and provide a new potential therapeutic target for the treatment of NSCLC and bone metastasis.