Galactooligosaccharides and Limosilactobacillus reuteri synergistically alleviate gut inflammation and barrier dysfunction by enriching Bacteroides acidifaciens for pentadecanoic acid biosynthesis.

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.

A single-cell and spatially resolved atlas of human osteosarcomas.

Osteosarcomas are intricate cellular ecosystems, where heterotypic interactions significantly influence disease progression and therapeutic outcomes. Despite their importance, a detailed understanding of their cellular composition and organizational structure remains elusive. In this study, we provide a comprehensive single-cell and spatially resolved transcriptomics analysis of human osteosarcomas. We construct a cellular meta-map to dissect spatial transcriptomic data, unveiling a detailed atlas of osteosarcoma compositional subgroups. We meticulously characterize the unique gene signatures and functional states of each subgroup and investigate the impact of chemotherapy on these cellular subpopulations. Additionally, our spatial transcriptomics analysis identifies a distinct spatial niche, located at the forefront of tumor necrotic zones, potentially associated with chemotherapy resistance. We also delve into the crosstalk between different cellular subgroups. This study furnishes a comprehensive transcriptional atlas of osteosarcoma's cellular architecture, enriching our comprehension of its complexity and laying the groundwork for more targeted therapeutic approaches.

Single-cell transcriptomic insights into chemotherapy-induced remodeling of the osteosarcoma tumor microenvironment.

PURPOSE: Neoadjuvant chemotherapy serves as an effective strategy for treating osteosarcoma (OS) not only by targeting cancerous cells but also by influencing the tumor's immune and stromal elements. Gaining insights into how chemotherapy reshapes the tumor's local environment is crucial for advancing OS treatment protocols. METHODS: Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy. RESULTS: The results revealed that chemotherapy caused the remaining OS cells to express higher levels of genes associated with stemness. Additionally, this process enhances the presence of cancer-associated fibroblasts, increasing their ability to modify the extracellular matrix (ECM). Chemotherapy also increases the number of endothelial cells, albeit with compromised differentiation capabilities. Importantly, the treatment reduced the immune cell population, including myeloid and T/NK cells, particularly impacting the subpopulations with tumor-fighting capabilities. CONCLUSION: These findings highlight the complex reaction of the tumor environment to chemotherapy, providing valuable insights into how chemotherapy influences OS cells and the tumor microenvironment (TME). This knowledge is essential for understanding OS resistance mechanisms to treatments, potentially guiding the development of novel therapies for managing advanced OS.

The interval between staged bilateral total knee arthroplasties does not affect early complications of the second knee or long-term function of the first and second knees.

BACKGROUND: This study explored the optimal time interval between staged bilateral total knee arthroplasty (BTKA) to minimize early complications of the second TKA and maximise the long-term function of the first and second knees. METHODS: We retrospectively reviewed 266 patients who underwent staged BTKA between 2013 and 2018. Groups 1-4 had time intervals between BTKAs of 1-6, 6-12, 12-18, and 18-24 months, respectively. Demographics, postoperative complications within 90 days of the second TKA, Knee Society Score (KSS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were compared among the groups. RESULTS: In total, 54, 96, 75, and 41 patients were assigned to groups 1-4, respectively. Although group 1 had the highest overall complication rate (11.11%), there was no significant difference in the complication rate among the four groups. Also, no significant differences were found among the four groups in functional and patient-reported outcomes, in either the first or second knee at 5 years postoperatively, including KSS-knee, KSS-function, WOMAC-pain, WOMAC-stiffness, and WOMAC-physical function. The interval between BTKA did not influence complications or the function of the second knee. The TKA type (posterior-stabilised vs. medial-pivot) and age did not correlate significantly with any scores. CONCLUSIONS: There was no group difference in early complications of the second TKA, and postoperative function was equivalent between the two knees and did not vary by the interval between surgeries. The results of this study give surgeons and patients more choices. If patients cannot tolerate severe symptoms in the contralateral knee after the first TKA, the second TKA should be performed as early as possible. If knee joint function is not well recovered after the first TKA, and patients are anxious to undergo the second TKA, surgeons can advise patients to postpone the operation based on these results.

Hidden blood loss and its influencing factors after cement augmentation for vertebral metastasis.

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.

Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p.

BACKGROUND: GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. METHODS: GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments. RESULTS: The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression. CONCLUSION: Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.

LncRNA CASC15 activated by TCF12 promote colorectal cancer progression via EMT.

BACKGROUND: Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. LncRNA CASC15 has also been found to play a vital role in malignant tumors. OBJECTIVE: Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of EMT and to clarify the reasons for its up-regulated expression in CRC. METHODS: Quantitative real-time PCR was performed to evaluate the expression of CASC15 in CRC. The biology function of CASC15 on CRC was assessed by in vitro experiments, including CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal transition (EMT). RESULTS: We found that CASC15 was remarkably upregulated in CRC and positively correlated with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically, TCF12 activates CASC15 transcription to mediate its up-regulation, which activates EMT and promotes CRC progression. CONCLUSION: Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC. CASC15 may be a new molecular marker and target for CRC.

Risk factors for pulmonary cement embolism after percutaneous vertebroplasty and radiofrequency ablation for spinal metastases.

Objective: Pulmonary cement embolism is a rare but underestimated complication of vertebroplasty due to the relative lack of study and examination. This study aims to investigate the incidence of pulmonary cement embolism in patients with spinal metastasis who undergo PVP with RFA and to analyze the relative risk factors. Methods: A total of 47 patients were retrospectively included and classified into pulmonary cement embolism (PCE) group and non-pulmonary cement embolism (NPCE) group by comparing pre- and postoperative pulmonary CT scan images. The demographic and clinical information of the patients was obtained. Demographic data in the two groups were compared using the chi-square test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was used to identify risk factors related to pulmonary cement embolism. Results: Pulmonary cement embolism was detected in 11 patients (23.4%), and all patients were asymptomatic and followed up regularly. Risk analysis showed that multiple segments (≥3, p=0.022), thoracic vertebrae (p=0.0008), and unipedicular puncture approach (p=0.0059) were risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra (p<0.0001). Vein leakage of cement was related to the integrity of the vertebral cortex. Conclusion: The number of involved vertebrae, lesion location, and puncture approach are independent risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra. Surgeons should consider these factors when formulating therapeutic strategies.

Robust, Flame-Retardant, and Anti-Corrosive Waterborne Polyurethane Enabled by a PN Synergistic Flame-Retardant Containing Benzimidazole and Phosphinate Groups.

Waterborne polyurethanes (WPUs) have attracted great interest owing to their environmentally friendly properties, and are wildly applied in production and daily life. However, waterborne polyurethanes are flammable. Up to now, the challenge remains to prepare WPUs with excellent flame resistance, high emulsion stability, and outstanding mechanical properties. Herein, a novel flame-retardant additive, 2-hydroxyethan-1-aminium (2-(1H-benzo[d]imidazol-2-yl)ethyl)(phenyl)phosphinate (BIEP-ETA) has been synthesized and applied to improve the flame resistance of WPUs, which has both phosphorus nitrogen synergistic effect and the ability to form hydrogen bonds with WPUs. The WPU blends (WPU/FRs) exhibited a positive fire-retardant effect in both the vapor and condensed phases, with significantly improved self-extinguishing performance and reduced heat release value. Interestingly, thanks to the good compatibility between BIEP-ETA and WPUs, WPU/FRs not only have higher emulsion stability, but also have better mechanical properties with synchronously improved tensile strength and toughness. Moreover, WPU/FRs also exhibit excellent potential as a corrosion-resistant coating.

Molecular Dynamics Simulation Study on the Influence of the Abrasive Flow Process on the Cutting of Iron-Carbon Alloys (α-Fe).

The plastic deformation behavior and microstructural changes in workpieces during ultra-precision machining have piqued the interest of many researchers. In this study, a molecular dynamics simulation of nano-cutting iron-carbon alloy (α-Fe) is established to investigate the effects of the fluid medium and cutting angle on workpiece temperature, friction coefficient, workpiece surface morphology, and dislocation evolution by constructing a molecular model of C12H26 as a fluid medium in the liquid phase using an innovative combined atomic approach. It is demonstrated that the presence of the fluid phase reduces the machining temperature and the friction coefficient. The cutting angle has a significant impact on the formation of the workpiece's surface profile and the manner in which the workpiece's atoms are displaced. When the cutting angle is 0°, 5°, or 10°, the workpiece's surface morphology flows to both sides in a 45° direction, and the height of atomic accumulation on the workpiece surface gradually decreases while the area of displacement changes increases. The depth of cut increases as the cutting angle increases, causing greater material damage, and the presence of a fluid medium reduces this behavior. A dislocation reaction network is formed by the presence of more single and double-branched structures within the workpiece during the cutting process. The presence of a fluid medium during large-angle cutting reduces the number of dislocations and the total dislocation length. The total length of dislocations inside the workpiece is shorter for small angles of cutting, but the effect of the fluid medium is not very pronounced. Therefore, small cutting angles and the presence of fluid media reduce the formation of defective structures within the workpiece and ensure the machining quality.

Effect of Negative Pressure Wound Therapy on Surgical Site Infections following Stoma Reversal in Colorectal Surgery: A Meta-Analysis.

BACKGROUND: Surgical site infections (SSI) are common complications after surgery, which cause other complications and increase medical costs. However, the effect of negative-pressure wound therapy (NPWT) for the prevention of SSI at stoma reversal remains inconclusive, with controversial results. This meta-analysis aimed to evaluate the safety and efficacy of NPWT following stoma reversal in colorectal surgery to prevent SSI and other wound complications. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases for articles published up to July 2022 and identified relevant studies reporting the NPWT administration following stoma reversal in colorectal surgery compared with non-pressure dressing. The primary outcome was the incidence of SSI, and the secondary outcomes were hematoma, seroma, and length of hospital stay (LOS). RESULTS: Nine studies were included in the meta-analysis, with 825 patients with (n = 310) or without (n = 515) NPWT. Pooled SSI rate was lower in the NPWT group than in the non-pressure dressing group (OR = 0.50; 95% CI: 0.29, 0.84; P = 0.01). There was no significant effect on hematoma (OR = 0.21; 95% CI: 0.03, 1.27; P = 0.09), seroma (OR = 0.26; 95% CI: 0.05, 1.28; P = 0.1) and LOS (MD = -0.16, 95% CI: -0.83, 0.51; P = 0.64). CONCLUSION: The use of NPWT following stoma reversal in colorectal surgery reduced the incidence of SSI. However, this conclusion needs to be interpreted with caution, and further studies should be conducted to confirm in higher-quality RCTs.

Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier.

Background: Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC. Methods: A mouse cecum orthotopic CRC model combined with high-fat diet (HFD) feeding, was established to mimic liver metastasis in CRC in obese patients. The effects of Dachaihu decoction (DCHD), a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease, and of the conventional prescription medicine obeticholic acid (OCA) were evaluated. HFD-induced obesity, hyperlipidemia, and CRC liver metastasis were assessed, along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues. The effects of DCHD and OCA on HFD-induced outcomes were evaluated, and human umbilical vein endothelial cells (HUVECs) treated with bile acids (BAs) and DCHD were used to study the underlying mechanisms in vitro. Results: HFD-mediated obesity and hyperlipidemia promoted CRC metastasis, accompanied by disruption of the gut vascular barrier (GVB) and altered bile acid (BA) metabolism. DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC, improving overall survival. Those effects of DCHD were equivalent to or better than those of OCA. DCHD regulated the expression of genes of BA metabolism and tight junctions (TJ) to prevent HFD-induced disruption of the GVB. In HUVECs, DCHD prevented the increases in intracellular Ca2+ and accumulation of reactive oxygen species induced by primary conjugated BAs, assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins, thereby maintaining the integrity of the endothelial barrier. Conclusions: The data provide a link between hypernutrition and GVB disruption, which contributes to high liver metastasis in patients with CRC. DCHD may represent a novel therapy in CRC, and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.

Osteofibrous dysplasia-like adamantinoma: A case report and literature review.

Abstract background: Osteofibrous dysplasia-like adamantinoma (OFD-like adamantinoma), classical adamantinoma and dedifferentiated adamantinoma were previously considered to be three subtypes of adamantinoma of long bones. In the 5th edition of the World Health Organization (WHO) classification of bone tumors in 2020, OFD-like adamantinoma was newly proposed and classified as an intermediate-locally aggressive tumor in other mesenchymal tumors of bone. OFD-like adamantinoma is rare, accounting for only 0.4% of all primary bone tumors. OFD-like adamantinoma is often misdiagnosed due to the insufficient understanding of it. Here we report a case of OFD-like adamantinoma treated in our hospital with a literature review. Case presentation: The patient, a 14-year-old male, had swelling in his right leg with intermittent pain for one year. Plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. Based on the radiological and histological examinations, a diagnosis of OFD-like adamantinoma was suspected. After admission, the patient underwent tumor resection of the right tibia, free transplantation of the left fibula and internal fixation. After resection of the tumor, the wound recovered well, the vital signs were stable, and activity was normal. The patient has been followed up for more than a year with no recurrence or distant metastasis. Conclusion: OFD-like adamantinoma is a rare primary bone tumor with nonspecific clinical features. Imaging examination can demonstrate the lesion and help diagnosis. The pathological discovery of epithelioid tissue is the key evidence for diagnosis.