Background This study evaluated the efficacy of a perioperative multimodal blood management strategy—combining erythropoietin, iron supplementation, and restrictive transfusion protocols—in patients undergoing surgery for hip bone tumors, to optimize their perioperative care. Methods We conducted a retrospective analysis of 38 patients who underwent hip bone tumor surgery between January 2021 and February 2025. Based on inclusion and exclusion criteria, patients were divided into a control group (n = 24) and a multimodal management group (n = 14). We compared baseline characteristics, preoperative laboratory results, surgical and postoperative data, dynamic hemoglobin changes, FACIT-Fatigue scores, and Harris Hip Scores between the groups. Results Preoperative hemoglobin was lower and surgical duration was longer in the multimodal management group compared to the controls (both p < 0.05). At one month postoperatively, the multimodal group demonstrated significantly greater improvement in both FACIT-Fatigue scores (5.79 ± 2.01 vs. 3.00 ± 0.78, p < 0.05) and Harris Hip Scores (30.57 ± 6.03 vs. 25.25 ± 6.46, p < 0.05). By three months postoperatively, scores between the two groups were comparable (p > 0.05). Conclusions Despite lower preoperative hemoglobin and more complex surgeries, the multimodal blood management strategy facilitated superior early functional recovery and accelerated rehabilitation at a critical postoperative time point.

This case report describes a 67-year-old male with confirmed overlap syndrome of rheumatoid arthritis (RA) and systemic sclerosis (SSc), exhibiting fibrillarin autoantibody positivity. Therapeutic intervention with methylprednisolone, methotrexate, and adjuvant medications resulted in substantial amelioration of articular symptoms. This case underscores the potential diagnostic and prognostic utility of fibrillarin autoantibodies in SSc, while highlighting the rarity of RA-SSc overlap syndrome with concurrent fibrillarin autoantibody expression.

OBJECTIVE:This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles. METHODS:Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments. RESULTS:Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production. CONCLUSION:The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.

Liver fibrosis is a key contributor to hepatic disease-related mortality. Exosomes derived from mesenchymal stem cells (MSCs) have been revealed to improve liver fibrosis. To explore the effect and mechanism of MSC-derived exosomal miR-26a on liver fibrosis, exosomes were separated from bone marrow-derived MSCs (BMSCs) and used to treat with LX2 cells. The miR-26a level was decreased in BMSC-derived exosomes. Treatment with exosomes isolated from human BMSCs transfected with miR-26a mimics (miR-26a mimic-Exo) decreased the 5-ethynyl-2'-deoxyuridine-positive cell rate, the protein level of α-SMA and collagen I, and the glutathione (GSH) level but enhanced the apoptosis rate and the reactive oxide species (ROS) level in LX2 cells, which were reversed by the treatment of deferoxamine. Mechanically, miR-26a directly bound SLC7A11 mRNA and negatively modulated the level of SLC7A11 in LX2 cells. Overexpression of SLC7A11 reversed the miR-26a mimic-Exo-induced alterations in the level of ROS, Fe2+, malonaldehyde, and GSH in LX2 cells. In vivo, miR-26a mimic-Exo decreased the level of SLC7A11 and attenuated CCL4-induced liver fibrosis. Collectively, miR-26a mimic-Exo induced ferroptosis to alleviate liver fibrosis by regulating SLC7A11, which may provide new strategies for the treatment of liver fibrosis, and even other relevant diseases.

Background Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. Methods This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. Results The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, −0.64%; 97.5% CI, −2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, −10.8%; 97.5% CI, −14.0% to −8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. Conclusions This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Gastric cancer (GC), a highly prevalent gastric cancer, has high-risk mortality. Thus, investigating strategies to counteract its growth is important to provide theoretical guidance for its prevention and treatment. It has been pointed out that abnormal expression of microRNAs (miRNAs) serves as noninvasive biomarkers for GC. This present study probed into the role of miR-622 and the NUAK family SNF1-like kinase 1 (NUAK1). Methods Five mRNA datasets (GSE64916, GSE118916, GSE122401, GSE158662, and GSE159721) and one miRNA dataset (GSE128720) from the Gene Expression of Omnibus (GEO) database were used to analyze the differentially expressed miRNAs and mRNA in GC and noncancer samples. Further, western blot, real-time quantitative PCR (qRT-PCR), reactive oxygen species (ROS) assay kit experiments, and wound healing assay, together with in vivo experiments, were performed. Results miR-622 was downregulated, and NUAK1 was upregulated in GC, and NUAK1 was a potential target of miR-622. Knocking down NUAK1 decreased GC cell proliferation and migration but increased oxidative stress in vitro and inhibited the development of tumor in vivo, while miR-622 acted to suppress the action of NUAK1 through the miR-622/NUAK1/p-protein kinase B (Akt) axis, thereby inhibiting the occurrence of GC. Conclusion miR-622 and NUAK1 demonstrated potential for being targets and biomarkers for GC treatment.

This study aimed to retrospectively analyze the features of contrast-enhanced ultrasound (CEUS) of renal masses that cannot be detected by conventional ultrasound (CUS). The data of 264 patients who underwent CEUS for renal lesions from January 2016 to December 2019 were retrieved. Of these, 16 patients with renal masses which were not detected by CUS were included in the final analysis. The corresponding characteristics of CEUS were evaluated, including intensity of enhancement, homogeneity, wash-in and wash-out patterns, and perilesional rim-like enhancement. Of the 16 patients, 10 patients had clear cell renal cell carcinoma (ccRCC) and 6 patients had urothelial carcinoma of the renal pelvis (UCRP). Compared with the location on non-enhanced computed tomography (CT) scan, all tumors were detected on CEUS. Most (7/10) of the ccRCCs appeared as hyperenhancement, homogeneous enhancement, synchronous-in, and no perilesional rim-like enhancement. Most (4/6) of the UCRPs appeared as isoenhancement, slow-in, fast-out, and no perilesional rim-like enhancement. CEUS may be helpful in the diagnosis and differential diagnosis of renal tumors which were not observed on CUS, and it might be an alternative method for some patients when contrast-enhanced computed tomography (CECT) or magnetic resonance imaging (MRI) cannot be performed.

A two-dimensional (2D) cell culture-based model is widely applied to study tumorigenic mechanisms and drug screening. However, it cannot authentically simulate the three-dimensional (3D) microenvironment of solid tumors and provide reliable and predictable data in response to in vivo, thus leading to the research illusions and failure of drug screening. In this study, honeycomb-like gelatin methacryloyl (GelMA) hydrogel microspheres are developed by synchronous photocrosslinking microfluidic technique to construct a 3D model of osteosarcoma. The in vitro study shows that osteosarcoma cells (K7M2) cultured in 3D GelMA microspheres have stronger tumorous stemness, proliferation and migration abilities, more osteoclastogenetic ability, and resistance to chemotherapeutic drugs (DOX) than that of cells in 2D cultures. More importantly, the 3D-cultured K7M2 cells show more tumorigenicity in immunologically sound mice, characterized by shorter tumorigenesis time, larger tumor volume, severe bone destruction, and higher mortality. In conclusion, honeycomb-like porous microsphere scaffolds are constructed with uniform structure by microfluidic technology to massively produce tumor cells with original phenotypes. Those microspheres could recapitulate the physiology microenvironment of tumors, maintain cell-cell and cell-extracellular matrix interactions, and thus provide an effective and convenient strategy for tumor pathogenesis and drug screening research.

Objective and Aims:To assess percutaneous vesselplasty's safety and efficacy in treating pathological vertebral compression fractures (VCFs). Subjects and Methods:This retrospective review covered nine patients with an equal number of symptomatic pathological VCFs treated with vesselplasty. The study assessed the patients' pain scores, subjective conditions, imaging guidance, and incidence of procedure-related complications. Results:The VCFs were at the T4 and L5 spine regions. The procedure success rate was 100%. In 88.89% (8/9) of the examined cases, there was a posterior vertebral body or pedicle involvement or both. Two patients with high thoracic VCFs underwent combined computed tomography and mobile C-arm fluoroscopy guidance. The other patients underwent digital subtraction angiography guidance. The average visual analog scale (VAS) score and the Oswestry Disability Index (ODI) before the treatment were 7.78 ± 0.67 standard deviation (SD) and 75.45 ± 7.55, respectively. The average VAS score and ODI 3 months after the treatment were 2.67 ± 0.50 (SD) and 32.45 ± 6.19 (P < 0.001), respectively. There were no recorded cases of symptomatic cement leakage or other operation-associated complications. Conclusions:Percutaneous vesselplasty appears to be a safe and effective minimally invasive local treatment for pathological VCFs. This approach may offer benefits in improving pain, mobility, and function and minimizing the bone cement leakage rate while providing a safe and effective alternative treatment for pathological VCFs.

Background:Chordoma is a rare malignant bone tumor with high recurrence and metastasis rates. Little is known about the mutational process of this incurable disease. The aim of our research was to explore the potential driver genes and signal pathways in the pathogenesis of chordoma and provide a new idea for the study of molecular biological therapy of chordoma.Methods:We performed whole-exome-sequencing (WES) on 8 sacrum chordoma tissue samples (matched to peripheral blood samples that had been drawn from patients before surgery) to identify genetic alterations in Chinese patients. We analyzed the sequencing data from known driver genes, pathway enrichment analysis and significantly mutated genes (SMGs) after quality control of sequencing, comparison of reference genomes, analysis of mutations and identification of somatic mutations. Immunohistochemistry staining, Sanger sequencing and GeneChip were used to verify the related genes obtained from the analysis of sequencing data.Results:The driver genes Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA), Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), and Phosphatase And Tensin Homolog (PTEN) were enriched in the Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway and could be potential therapeutic targets for the treatment of sacrum chordoma. The significantly mutated gene Claudin 9 (CLDN9) may play a critical role in the development and progression of sacrum chordoma.Conclusions:Collectively, our results identified the genetic signature of sacrum chordoma and could be used to develop a potential promising therapeutic strategy for the treatment of sacrum chordoma in Chinese patients.

Bryostatin 8 Si A ring: geminal bis(silyl) Prins cyclization C16-C17: silicon-protected RCM

High-voltage-activated (HVA) Ca2+ channels are widely expressed in the nervous system. They play an important role in pain conduction by participating in various physiological processes such as synaptic transmission, changes in synaptic plasticity, and neuronal excitability. Available evidence suggests that the HVA channel is an important therapeutic target for pain management. In this review, we summarize the changes in different subtypes of HVA channel during pain and present the currently available evidence from the clinical application of HVA channel blockers. We also review novel drugs in various phases of development. Moreover, we discuss the future prospects of HVA channel blockers in order to promote "bench-to-bedside" translation.

BACKGROUND:Chordoma is a low-grade aggressive bone tumor with a high local recurrence. MicroRNAs (miRNAs) have been reported to play crucial roles in the development of chordoma. Our previous study has shown miR-1290 is associated with muscle invasion and the prognosis of chordoma. However, the underlying mechanism of miR-1290 in chordoma remains unclear. In this study, we aimed to explore the function of miR-1290 in the biological behaviors of chordoma.METHODS:Sixteen sacral chordoma samples and 10 fetal nucleus pulposus specimens were collected for the detection of miR-1290 and Robo1 at the First Affiliated Hospital of Soochow University. Bioinformatic analysis and a luciferase reporter assay was used to verify the interaction between miR-1290 and the target gene robo1 in chordoma. Effects of miR-1290 expression on chordoma cell proliferation and invasion were explored by clone formation and Transwell assay in vitro. The underlying mechanisms of miR-1290 and Robo1 in chordoma cell proliferation and invasion were also explored in the U-CH1 cell line.RESULTS:In vitro functional analysis, including clone formation, and Transwell assays indicated overexpression of miR-1290 significantly suppressed chordoma cell proliferation and invasion. Bioinformatic analysis revealed Robo1 as a potential target of miR-1290, and luciferase reporter assays demonstrated the association between miR-1290 and the Robo1 gene in U-CH1 cells. Robo1 was further confirmed to be up-regulated in chordoma tissues by immunohistochemistry (IHC), which is negatively correlated with miR-1290 expression in chordoma tissue. Additionally, we found down-regulation of miR-1290 could induce the expression of Robo1 in chordoma cells, while the elevation of miR-1290 expression could inhibit Robo1 expression in chordoma cells.CONCLUSIONS:miR-1290 inhibits chordoma cell proliferation and invasion by negatively regulating the Robo1 gene.

Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adenoassociated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.

This retrospective cohort study aims to evaluate the effects of introducing the O-arm-based navigation technique into the traditional posterior lumbar interbody fusion (PLIF) procedure treating elderly patients with three-level lumbar degenerative diseases.

Chordoma is a rare bone tumor with high recurrence rate, but the mechanism of its development is unclear. Long non-coding RNAs(lncRNAs) are recently revealed to be regulators in a variety of biological processed by targeting on mRNA transcription. Their expression profile and function in chordoma have not been investigated yet. In this study, we firstly performed the comprehensive analysis of the lncRNA and coding genes expression analysis with three chordoma samples and three fetal nucleus pulposus tissues. lncRNA and gene microarrays were used to determine the differentially expressed lncRNAs and protein coding genes. 2786 lncRNAs and 3286 coding genes were significantly up-regulated in chordoma, while 2042 lncRNAs and 1006 coding genes were down-regulated. Pearson correlation analysis was conducted to correlate differentially expressed lncRNAs with protein coding genes, indicating a comprehensive lncRNA-coding gene co-expression network in chordoma. Cis-correlation analysis showed that various transcripts of MEG3 and MEG8 were paired with the most differentially expressed gene DLK1. As located in the same locus, we further analyzed the miRNA clusters in this region, and identified that 61.22% of these miRNAs were significantly down-regulated, implying the silence of the imprinted gene cluster DLK1-MEG3. Overexpression of MEG3 suppressed the proliferation of chordoma cells. Our study pointed out the potential role of lncRNAs in chordoma, presented the lncRNA-coding genes co-expression profile, and revealed that imprinted gene cluster DLK1-MEG3 contributes to the pathogenesis of chordoma development.

Chordoma is a rare, locally aggressive neoplasm of bone, usually with poor prognosis. The treatment for chordoma has been unsatisfactory for decades. MiRNAs were recently introduced into this field and provided new insights to the pathogenesis and pathophysiology of chordoma. However, molecular basis of chordoma remains ambiguous up to now. This research aims to discover novel miRNA molecules as potential biomarkers and therapeutic targets. We measured the expression of miRNA-1290 in chordoma tissues and fetal nucleus pulposus tissues by quantitative real-time PCR. Further, we analyzed its association with the clinical features as well as the prognosis of patients. The expression of miRNA-1290 in chordoma samples was significantly lower than fetal nucleus pulposus samples (P=0.026). Low expression of miRNA-1290 contributed to tumor invasion into surrounding muscle (P=0.013), while no obvious significance was identified between miRNA-1290 expression and patients' age, gender, tumor location and size (P>0.05). Log-rank test showed that low-level miRNA-1290 expression had a prominent impact on the patients' RFS (P=0.004). Conclusively, miRNA-1290 might be a valuable prognostic biomarker and efficient therapeutic target for sacral chordoma.

Chordoma is a rare aggressive bone tumor arising from remnants of the notochord, and patients with chordoma have a poor prognosis. However, the unique expression profiles of microRNAs (miRNAs/miRs) and their downstream signaling pathways in chordoma remain incompletely characterized. The aim of the present study was to delineate the global miRNA expression profile and associated signaling networks in chordoma. miRNA profiling was performed on chordoma and fetal notochord tissues. Differentially expressed miRNAs in chordoma were analyzed using microarrays with hierarchical clustering analysis. The target genes of the differentially expressed miRNAs were predicted, and Gene Ontology (GO) and pathway analyses were performed for the intersecting genes. A total of 42 miRNAs were significantly dysregulated in chordoma compared with that in fetal nucleus pulposus tissues. The expression of hsa-miR-21-3p, hsa-miR-150-5p, hsa-miR-1290 and hsa-miR-623 were validated using the reverse transcription-quantitative polymerase chain reaction. On the basis of the intersection predicted by three databases (Targetscan, microRNA.org and PITA), 10,292 potential miRNA targets were identified. Bioinformatic analyses suggested that these dysregulated miRNAs and their predicted targets were functions of signaling pathways in cancer, the mitogen-activated protein kinase signaling pathway, regulation of actin cytoskeleton, focal adhesion and endocytosis. In particular, human (hsa-) miR-185-5p was identified as a crucial miRNA in chordoma development via the Wnt signaling pathway. The results of the present study provide a comprehensive expression and functional profile of differentially expressed miRNAs associated with chordoma. This profile may serve as a potential tool for biomarker and therapeutic target identification in patients with chordoma.

A 17-year-old woman presented with a 1-year history of sacrococcygeal pain, accompanied by difficulty in urination and defecation for 1 month. Computed tomography and magnetic resonance imaging showed a huge osteolytic and expansile lesion involving the sacrum (Fig. 1). This mass (18×20 cm in size) extended anteriorly into the pelvic cavity, compressing the bladder and bowel (Fig. 1). Computed tomography-guided biopsy demonstrated that the tumor was a giant-cell tumor of bone. Preoperative angiography and embolization were used to selectively block the main arteries feeding the tumor (Fig. 2). The patient then underwent a successful marginal resection via an isolated posterior approach. As often happens with giant-cell tumor [ [1] Shen C.C. Li H. Shi Z.L. Tao H.M. Yang Z.M. Current treatment of sacral giant cell tumour of bone: a review. J Int Med Res. 2012; 40: 415-425 Crossref PubMed Scopus (13) Google Scholar ], the patient had a local recurrence at 30 months. Fig. 2(Left and Right) The arteriogram before and after the arterial embolization. View Large Image Figure Viewer Download Hi-res image

Chordoma is a rare and low-malignant neoplasm which is considered to arise from notochord remnants. Due to its large resistance to chemotherapy and radiotherapy, surgical resection so far is the prior treatment for chordoma. However, the recurrence rate is high even after complete surgical resection. Recently, targeted cancer therapy has been demonstrated to be effective in several other tumors, while the related research on chordoma is rare. Mitogen-activated protein kinase signaling pathway is acknowledged to participate in tumor development, in which Raf-1 and extracellular regulated protein kinase 1/2 (ERK1/2) play vital roles. In this study, we evaluated the expression of Raf-1 and ERK1/2 by immunohistochemical staining in 42 chordoma tissue and 16 distant normal tissue. Moreover, we also investigated the correlations of Raf-1 and ERK1/2 expression with clinical features in sacral chordoma. Expression of Raf-1 and ERK1/2 was both significantly higher in sacral chordoma tissue than distant normal tissue (P = 0.008, P = 0.019). Raf-1 positive expression was related to surrounding muscle invasion (P = 0.032) and chordoma recurrence (P = 0.002), but the results did not indicate any association with patients' age, gender, tumor size and location. ERK1/2 was associated with tumor size (P = 0.044) instead of other clinical factors (P > 0.05). Spearman correlation test showed close relation between ERK1/2 and Raf-1 (P = 0.001, r = 0.518). Kaplan-Meier survival Curve and log-rank test showed that Raf-1 positive expression was associated with shorter continuous disease-free survival time (CDFS) (P = 0.001), while ERK1/2 had no relation to CDFS (P = 0.961). Conclusively, Raf-1 may be an important biomarker in predicting the prognosis of chordoma patients.