Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. METHODS: Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. RESULTS: From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. CONCLUSIONS: Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

Global trends in the research on Legg-Calve-Perthes disease in Web of Science.

Background: Legg-Calve-Perthes disease (LCPD) is a form of idiopathic femoral head necrosis that can lead to permanent femoral head deformities and premature osteoarthritis in children under the age of 15. Its pathogenesis is utterly and remains to be clarified. Although many research publications on LCPD have emerged during the last few decades, few systematic bibliometric analyses of these articles have been reported. Methods: A bibliometric analysis was performed to investigate the development processes and hotspots, as well as the collaboration and influence among countries, institutions, authors, journals, and keywords of papers relevant to LCPD from the Web of Science Core Collection (WoSCC) during the period from 1 January 2000 to 30 June 2023. Results: A total of 2,205 researchers from 916 institutions across 53 countries/regions have contributed to 673 papers published in 199 academic journals. The research on LCPD has shown significant fluctuations but a gradual increase in the number of articles published over the last two decades. The United States leads in the number of publications of LCPD, with the Texas Scottish Rite Hospital for Children being the most productive institution. English, as the most widely used language in the world, was undoubtedly the most popular language. Herring JA, who acted as both the corresponding and first author, has contributed to the most co-cited papers published. The most number of LCPD papers are published in the Journal of Pediatric Orthopaedics, whereas the Journal of Bone and Joint Surgery American Volume garnered the highest total citations, indicating the great importance of these two journals in the field of orthopedics. The most frequently used keywords in published articles were related to the symptoms, mechanisms, and prognosis, revealing the research focus of most scholars. Conclusion: Our research described the development trends and hotspots in the research field of LCPD and will help researchers make better decisions.

Analysis of the Genetic Model of the Extremely Narrow Channel Shallow Water Delta in DL-A Oilfield, Bohai Bay Basin.

In recent years, the oil and gas reserves discovered in shallow water deltas in China have continued to grow. The research on shallow water delta deposition models and depositional genesis is becoming more and more mature. In this latest discovery, a unique type of extremely narrow channel shallow water delta deposit was found at the top of the V oil group in the lower part of the Minghuazhen Formation during the Neogene period at DL-A Oilfield, located in the Bohai Bay Basin. The width of most single channels in this deposit measures between 100 and 200m, which is relatively rare and differs from existing research. To better understand this unique narrow channel shallow water delta deposit, a range of analysis methods were conducted including trace element analysis, major element analysis, grain size analysis, core observation, casting thin section observation, 3D seismic analysis, and other methods. These analyses were used to determine the sedimentary environment and sedimentary genesis of the deposit in the study area. The results show the following: (1) The top of the V oil group in the lower part of Minghuazhen Formation was deposited with a strong oxidizing environment. In the early stage, the climate was dry and cold, and gradually changed to warm and humid in the late stage. (2) Due to the frequent exposure to the surface, obvious weathered surfaces and sedimentary discontinuities were observed on the cores; the particle size analysis shows that the lamina types developed in the study area are clastic-clay laminae and clay-clastic laminae, which are mostly developed in shallow lakes area. (3) Observations of cores and thin sections also indicated that the hydrodynamic conditions frequently changed in the study area, alternating between strong and weak hydrodynamic conditions in a short period due to the alternating occurrence of flood and dry periods during the rainy season. Weak hydrodynamic conditions and slow water flow result in insufficient undercutting and sidecutting of rivers. The alternating occurrence of flood periods and dry periods has led to the development of crevasse splays and frequent river channel diversions, resulting in the inability of long-term stable development of the river channel. Besides, the change of water level has also led to the rebuilding of the river. Therefore, the multiple effects led to the formation of an extremely narrow channel shallow water delta. The accuracy of the sedimentary model is verified by a comparative study of the Shaliu River and Buha River in the modern Qinghai Lake. The new extremely narrow channels deposition model proposed this time further improves the deposition theory. At the same time, the modern depositional characteristics of the Shaliu River and Buha River also reveal the reservoir deposition between channels that cannot be distinguished by seismic data, providing guidance for the development of oil and gas in the study area.

A new insight of immunosuppressive microenvironment in osteosarcoma lung metastasis.

The lung is the primary organ for the metastasis of osteosarcoma. Although the application of neoadjuvant chemotherapy and surgery has remarkably improved the survival rate of patients with osteosarcoma, prognosis is still poor for those patients with metastasis. In this study, we performed further bioinformatics analysis on single-cell RNA sequencing (scRNA-seq) data published before, containing 75,317 cells from two osteosarcoma lung metastasis and five normal lung tissues. First, we classified 17 clusters, including macrophages, T cells, endothelial cells, and so on, indicating highly intratumoral heterogeneity in osteosarcoma lung metastasis. Next, we found macrophages in osteosarcoma lung metastasis did not have significant M1 or M2 polarizations. Then, we identified that T cells occupied the most abundant among all cell clusters, and found CD8+ T cells exhibited a low expression level of immune checkpoints in osteosarcoma lung metastasis. What is more, we identified C2_Malignant cells, and found CD63 might play vital roles in determining the infiltration of T cells and malignant cells in conventional-type osteosarcoma lung metastasis. Finally, we unveiled C1_Therapeutic cluster, a subcluster of malignant cells, was sensitive to oxfendazole and mevastatin, and the potential hydrogen-bond position and binding energy of oxfendazole-KIAA0907 and mevastatin-KIAA0907 were unveiled, respectively. Our results highlighted the power of scRNA-seq technique in identifying the complex tumor microenvironment of osteosarcoma lung metastasis, making it possible to devise precision therapeutic approaches.

High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification.

Background: Guanine nucleotide binding (G) protein subunit γ 4 (GNG4) is closely related to the malignant progression and poor prognosis of various tumours. However, its role and mechanism in osteosarcoma remain unclear. This study aimed to elucidate the biological role and prognostic value of GNG4 in osteosarcoma. Methods: Osteosarcoma samples in the GSE12865, GSE14359, GSE162454 and TARGET datasets were selected as the test cohorts. The expression level of GNG4 between normal and osteosarcoma was identified in GSE12865 and GSE14359. Based on the osteosarcoma single-cell RNA sequencing (scRNA-seq) dataset GSE162454, differential expression of GNG4 among cell subsets was identified at the single-cell level. As the external validation cohort, 58 osteosarcoma specimens from the First Affiliated Hospital of Guangxi Medical University were collected. Patients with osteosarcoma were divided into high- and low-GNG4 groups. The biological function of GNG4 was annotated using Gene Ontology, gene set enrichment analysis, gene expression correlation analysis and immune infiltration analysis. Kaplan-Meier survival analysis was conducted and receiver operating characteristic (ROC) curves were calculated to determine the reliability of GNG4 in predicting prognostic significance and diagnostic value. Functional in vitro experiments were performed to explore the function of GNG4 in osteosarcoma cells. Results: GNG4 was generally highly expressed in osteosarcoma. As an independent risk factor, high GNG4 was negatively correlated with both overall survival and event-free survival. Furthermore, GNG4 was a good diagnostic marker for osteosarcoma, with an area under the receiver operating characteristic curve (AUC) of more than 0.9. Functional analysis suggested that GNG4 may promote the occurrence of osteosarcoma by regulating ossification, B-cell activation, the cell cycle and the proportion of memory B cells. In in vitro experiments, silencing of GNG4 inhibited the viability, proliferation and invasion of osteosarcoma cells. Conclusion: Through bioinformatics analysis and experimental verification, high expression of GNG4 in osteosarcoma was identified as an oncogene and reliable biomarker for poor prognosis. This study helps to elucidate the significant potential of GNG4 in carcinogenesis and molecular targeted therapy for osteosarcoma.

Trends of denosumab-related publications in web of science.

Denosumab is a human monoclonal antibody that targets nuclear factor-kappa B ligand and is highly effective in blocking bone resorption. Bibliometrics can intuitively show the research development process, research status, research hotspots and development trend of a certain topic for researchers. This study assessed the course of research and development for denosumab in terms of publications over the past 2 decades. Web of Science databases were searched to identify publications related to research on denosumab from January 1, 2005 to December 31, 2022. The VOS Viewer software (version 1.6.17) and Bibliometrix package in R (version 4.1.3) were used in this study. There were 5119 denosumab-related publications during this period. The total number of citations of denosumab-related publications reached 94917. The most articles were published in the field of Endocrinology Metabolism. As an international language, English remains the most popular language for writing papers. Five of the top ten institutions originated in the USA. Through the VOS Viewer analysis, we found that the relationships between Amgen Inc. with its collaborations were grouped into 4 clusters, the USA was the mainland for research and development on denosumab, closely collaborating with many other countries, such as Canada, Japan, England, and China. Wagman RB from USA was the most prolific author with 119 publications. The journal with the most publications was Osteoporosis International (481 publications). The most cited article was "Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis" with 2053 citations. The clinical trial comprised 6 of the 10 most frequently cited publications, and the rest consisted of reviews. The most frequent keywords for publications since January 1, 2014 were "prevention" and "management," indicating that a number of prevention and management measures have been developed to regulate the use of denosumab in treating osteoporosis. Our research provided a comprehensive review of denosumab-related publications, suggesting that the development of denosumab is a long process and numerous clinical trials have been conducted before applications in clinical settings.

Analysis of scRNA-seq and bulk RNA-seq demonstrates the effects of EVI2B or CD361 on CD8+ T cells in osteosarcoma.

Osteosarcoma (OS) is a common primary malignant tumor of the bone in children and adolescents. The five-year survival rate is estimated to be ~70% based on the currently available treatment modalities. It is well known that tumor-infiltrating immune cells (TIICs) that are the most important components in the tumor microenvironment can exert a killing effect on tumor cells. Therefore, in the present study, 85 RNA-sequencing OS samples were categorized into high- and low-immune score groups with ESTIAMATE. Based on the immune score groups, 474 differentially expressed genes (DEGs) were acquired using the LIMMA package of R language. Subsequently, 86 DEGs were taken through univariate COX regression analysis, of which 14 were screened out by least absolute shrinkage and selection operator regression analysis. Furthermore, multivariate COX regression analysis was performed to obtain 4 DEGs. Finally, ecotropic virus integration site 2B (EVI2B) or CD361 gene was screened out via Kaplan-Meier analysis. In addition, CIBERSORT algorithm was used to evaluate the proportion of 22 kinds of TIICs in OS. Correlation analysis revealed that the high expression level of EVI2B can elevate the infiltrated proportion of CD8+ T cells. Moreover, analysis of single cell RNA-sequencing transcriptome datasets and immunohistochemical staining uncovered that EVI2B was mainly expressed on CD8+ T cells and that EVI2B could promote the expression of granzyme A and K of CD8+ T cells to exhibit a potent killing effect on tumor cells. Therefore, EVI2B was identified as a protective immune-related gene and contributed to good prognosis in OS patients.

UPLC/Q-TOF-MS-based Metabolomics Study of the Antiosteoporosis Effects of Vaccarin in Ovariectomized Mice.

Osteoporosis is a systemic and metabolic bone disease that usually occurs in postmenopausal women, which mainly manifests as bone loss and increased bone fragility that both facilitate fracture. However, few drugs for osteoporosis have shown good efficacy and limited side effects. Vaccarin has demonstrated its antiosteoporosis effects by inhibiting the formation and osteolytic activities of osteoclasts in our previous investigation. In this study, multivariate statistical analysis and ultrahigh-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry were used to analyze the serum metabolites of ovariectomized mice treated with or without vaccarin. As a result, 9 serum metabolites were identified as biomarkers. The metabolic levels of 3 crucial biomarkers, namely, lysophosphatidylcholine [22 : 6, (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)], 1-linoleoylglycerophosphocholine and 1-palmitoyl-Sn-glycero-3-phosphocholine, that were correlated with glycerophospholipid metabolism increased and then decreased significantly after vaccarin treatment. Molecular docking analysis and osteoclasts differentiation experiment further revealed that vaccarin may bind with phospholipase A2 and downregulated its activity to reduce the osteoclastogenesis. Therefore, the occurrence of osteoporosis is closely related with glycerophospholipid metabolism disorders, and vaccarin exerts antiosteoporosis effects by reducing the levels of glycerophospholipid metabolites.

Exploring the Nonlinear and Threshold Effects of Travel Distance on the Travel Mode Choice across Different Groups: An Empirical Study of Guiyang, China.

Examining how travel distance is associated with travel mode choice is essential for understanding traveler travel patterns and the potential mechanisms of behavioral changes. Although existing studies have explored the effect of travel distance on travel mode choice, most overlook their non-linear relationship and the heterogeneity between groups. In this study, the correlation between travel distance and travel mode choice is explored by applying the random forest model based on resident travel survey data in Guiyang, China. The results show that travel distance is far more important than other determinants for understanding the mechanism of travel mode choice. Travel distance contributes to 42.28% of explanation power for predicting travel mode choice and even 63.24% for walking. Significant nonlinear associations and threshold effects are found between travel distance and travel mode choice, and such nonlinear associations vary significantly across different socioeconomic groups. Policymakers are recommended to understand the group heterogeneity of travel mode choice behavior and to make targeted interventions for different groups with different travel distances. These results can provide beneficial guidance for optimizing the spatial layout of transportation infrastructure and improving the operational efficiency of low-carbon transportation systems.

Corrigendum: Single-cell transcriptomics reveals the complexity of the tumor microenvironment of treatment-naive osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2021.709210.].

ATG16L1 is a Potential Prognostic Biomarker and Immune Signature for Osteosarcoma: A Study Based on Bulk RNA and Single-Cell RNA-Sequencing.

BACKGROUND: Osteosarcoma is a common solid malignancy of the bone in children and adolescents, and its metastasis and recurrence are the principal causes of poor treatment outcomes. METHODS: Autophagy-related genes were used to cluster osteosarcoma patients by consensus clustering analysis using the GSE21257 database. Differentially expressed genes (DEGs) were identified by limma package. Multiple-gene risk signature was constructed using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression analyses. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine gene expression levels. Then, single-cell RNA-sequencing dataset GSE152048 were used to identify the correlation between the DEGs and effector molecules expressed in specific tumor-infiltrating immune cells. RESULTS: Two clusters were identified in the consensus clustering analysis, which were confirmed by principal component analysis. Limma analysis revealed that 15 genes were related, and 9 genes were screened using protein-protein interaction network and LASSO regression analysis. Cox regression analyses identified 5 genes. Combined with survival analysis, only the autophagy related 16 like 1 gene (ATG16L1) was significant. The results of qRT-PCR showed low expression levels of ATG16L1 in tumor cells group. Immune infiltration analysis revealed significantly lower expression of CD8+ T cells in the high ATG16L1 gene expression group. ScRNA-seq revealed that in the ATG16L1+ CD8 + T cell group, the expression of GZMB was lower, whereas the expression of ITGA1 was higher. These results showed that ATG16L1 is an immune-related gene, which is associated with poor prognosis in patients with osteosarcoma. CONCLUSION: ATG16L1 is a potential prognostic biomarker and immune signature and may be a therapeutic target for osteosarcoma.

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone.

Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

TMT-Based Proteomic Explores the Influence of DHEA on the Osteogenic Differentiation of hBMSCs.

Dehydroepiandrosterone (DHEA) has been revealed to implicate in facilitating osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and inhibiting osteoporosis (OP). However, the underlying molecular mechanism remains largely unknown. Here, we induced osteogenic differentiation of hBMSCs derived from elders using an osteogenic induction medium with or without DHEA. The results showed that osteogenic induction medium (OIM) with DHEA could significantly promote the proliferation and osteogenic differentiation of hBMSCs than OIM alone. By using a Tandem Mass Tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, we screened out 604 differentially expressed proteins (DEPs) with at least one unique peptide were identified [524: OIM vs. complete medium (CM), and 547: OIM+DHEA vs. CM], among these proteins, 467 DEPs were shared in these two different comparative groups. Bioinformatic analysis revealed these DEPs are mainly enriched in metabolic pathways. Interestingly, the expression levels of the DEPs in the metabolic pathways showed a more noticeable change in the OIM+DHEA vs. CM group than OIM vs. CM group. Moreover, the protein-protein interaction (PPI) network analysis revealed that three potential proteins, ATP5B, MT-CYB, and MT-ATP6, involved in energy metabolism, might play a key role in osteogenic differentiation induced by OIM+DHEA. These findings offer a valuable clue for us to better understand the underlying mechanisms involved in osteoblast differentiation of hBMSCs caused by DHEA and assist in applying DHEA in hBMSCs-based therapy for osteogenic regeneration.

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

A pH-responsive mesoporous silica nanoparticles-based drug delivery system with controlled release of andrographolide for OA treatment.

Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1ß-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.

The relationship between job stress and job burnout moderated by BDNF rs6265 polymorphism.

RATIONALE: Job stress can lead to job burnout, and BDNF polymorphism has been found to be involved in its psychopathological mechanism. Research needs a better understanding of the important role of gene × environment (i.e., BDNF polymorphism × job stress) interaction on job burnout. OBJECTIVE: This study aimed to explore how BDNF rs6265 polymorphism may moderate the relationship between job stress and job burnout. METHODS: Three hundred forty-one healthy participants (187 males and 154 females) from a Chinese university were included. The present study used a standardized questionnaire including demographic characteristics, job stress assessed by the House and Rizzo's Work Stress Scale, and job burnout assessed by the Maslach Burnout Inventory-General Survey. The BDNF rs6265 polymorphism was genotyped. RESULTS: Job stress showed a positive correlation with emotional exhaustion (p < 0.001), cynicism (p < 0.001), and reduced personal accomplishment (p < 0.01). The main effects of BDNF rs6265 polymorphism on emotional exhaustion and cynicism were significant [F(1,333) = 5.136, p = 0.024; F(1,333) = 4.175, p = 0.042, respectively]. The interaction between job stress and BDNF rs6265 on cynicism was significant (△ R2 = 0.013, p = 0.014) after controlling for age, sex, education, and position, indicating that individuals with BDNF rs6265 TT genotype showed higher level of cynicism when in high job stress. CONCLUSIONS: The results provided evidence for the association of BDNF gene rs6265 polymorphism, job stress, and their interaction with job burnout. Individuals with TT genotype in BDNF rs6265 might be susceptible to stressful situations, which would lead to cynicism.

Diagnostic Role of Selective Spinal Nerve Block in Treatment of Lumbar Spine Diseases by Percutaneous Endoscopic Technique.

AIM: To assess the role of our modified selective spinal nerve block (SSNB) procedure to predict the results of the subsequent Percutaneous endoscopic transforaminal lumbar surgeries (PETLS). MATERIAL AND METHODS: We retrospectively analyzed data of patients who underwent our modified SSNBs before PETLS from February 2013 to March 2018 Clinical outcome data were collected 3 days after PETLS and at follow-up visits. RESULTS: A total of 120 modified SSNB procedures (transforaminal-78 paravertebral-24, and interlaminar-18) in 92 patients presented positive response. The median follow-up period was 30.6 months. Based on Macnab criteria, the overall success rate (excellent and good results) was 83.7%. Fair and poor outcomes were observed in 10 and 5 patients, respectively. Patients with atypical extraforaminal herniations, and patients with two-level or multiple-level lumbar disc herniations or stenosis achieved desirable results after PETLS. There was significant improvement in the average VAS score for the leg three days after surgery (7.38±0.97 vs. 1.96 ±1.17, p < 0.05) and on follow-up visits (1.21 ± 0.83, p < 0.05). ODI was also significantly improved three days after surgery (37.20 ± 2.36 vs. 10.95 ± 2.25, p < 0.05 and at follow-up visits (8.90 ± 1.72, p < 0.05) CONCLUSION: The needle tip should be located closely near the intended compressed nerve via suitable approach combined with slowly injecting 1 ml lidocaine (1%) when performing our modified SSNB technique. It presents an alternative diagnostic procedure to identify the origin of pain of complicated lumbar diseases and to predict PETLS outcomes.

Effect of Composite Nanoparticle CeO2 on Myocardial Ischemic Re-Infusion of Cardio Myocyte Apoptosis in Mouse.

The myocardial I/R damage is very complicated. Apoptosis is considered to its a critical mechanism. During the cardiac muscle I/R process, oxygen-free radicals play a pivotal role. Arrhythmias, as well as enlargement of the area of myocardial infarction after cardiac muscle I/R process, are caused by adequate blast generated O2- ion free radicals. During the ischemia-reperfusion process, a large amount of O2- ion free radicals destroyed the cell structure, and it undergoes lipid peroxidation with unsaturated fatty acids that contain a large number of phospholipids in the cell membrane, causing membrane proteins such as ion channels and enzymes on the cell membrane. The activity of cell is reduced, which affects the function of cell membrane and organelle membrane, destroys its integrity and reduces fluidity.We observed the effects of cerium dioxide nanoparticles on glutathione peroxidase as well as superoxide dismutase, also propionate in myocardial tissue of I/R injury in the mouse. Its effects of malondialdehyde and apoptosis were explored to see its protective effect and to provide more preventive measures for ischemia-reperfusion injury.

Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy.

BACKGROUND: Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-ß that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported. RESULTS: We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-ß. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy. CONCLUSIONS: C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

Continuous Lumbar Sympathetic Blockade Enhances the Effect of Lumbar Sympatholysis on Refractory Diabetic Neuropathy: A Randomized Controlled Trial.

INTRODUCTION: There are a number of options for the symptomatic treatment of peripheral neuropathy, but the overall treatment outcomes remain unsatisfactory. METHODS: A total of 60 patients with refractory diabetic neuropathy were randomly assigned to two groups. Patients in Group A were treated with computed tomography (CT)-guided sympathetic neurolysis with alcohol, and patients in Group B were treated with a combined therapy of CT-guided catheterization to achieve continuous lumbar block for 4 weeks followed by neurolysis with alcohol administered via the catheter. The outcomes of these two treatment strategies were then analyzed in terms of pain relief, blood flow in the lower limb microcirculation, plasma levels of inflammatory mediators, and complications. RESULTS: The visual analog scale (VAS) pain scores of all patients after treatment decreased significantly at the different evaluation time points compared with pre-treatment values, with the intergroup analysis revealing that the VAS scores were lower in Group B patients than in Group A patients at all post-treatment time points. Skin temperature, capillary filling time, and blood oxygen saturation level were significantly improved in all patients at the 1- and 7-day post-treatment assessment compared to pre-treatment values, but patients in Group B showed a greater improvement. The plasma levels of inflammatory mediators were lower in all patients at the 7-day post-treatment assessment compared to pre-treatment values, with those of patients in Group B being statistically significantly lower than those of patients in Group A. CONCLUSION: Combined treatment with continuous lumbar sympathetic block followed by neurolysis with alcohol provided more benefit in all assessed outcomes than sympathetic alcohol neurolysis alone. The results show that the procedures were associated with satisfactory safety outcomes and sustained analgesic effects, thereby providing clinical evidence supporting the use of this novel treatment for patients with painful diabetic neuropathy.