Effect of Low-Dose Aspirin Use After Thermal Ablation in Patients with Hepatocellular Carcinoma: A Retrospective Study.

Purpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1-14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5-11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1-95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7-64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

68Ga-FAPI and 18F-FDG PET/CT Imaging in Langerhans Cell Histiocytosis for Recurrence and Therapeutic Response Assessment.

ABSTRACT: A 2-and-a-half-year-old boy with a previous history of Langerhans cell histiocytosis reached remission as assessed by 18F-FDG PET/CT. Routine follow-up 18F-FDG PET/CT revealed the appearance of new bone lesions in the right scapula and right ischium with abnormal FDG activity 3 months after the end of treatment, and Langerhans cell histiocytosis recurrence was considered. Meanwhile, these lesions also showed increased FAPI uptake. After adjusting the chemotherapy regimen, both FDG and FAPI uptake almost disappeared in these lesions.

Mendelian randomization provides causal association between COVID-19 and thyroid cancer: insights from a multi-cancer analysis.

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 virus has caused over 600 million confirmed infections and more than 6.8 million deaths worldwide, with ongoing implications for human health. COVID-19 has been extensively documented to have extrapulmonary manifestations due to the widespread expression of necessary ACE2 receptors in the human body. Nevertheless, the association between COVID-19 and cancer risk remains inadequately explored. This study employs Mendelian randomization (MR) methods to examine the causal relationship between genetic variations associated with COVID-19 and the risk of developing cancer. The findings indicate that COVID-19 has negligible impact on most cancer risks. Interestingly, a higher COVID-19 impact is associated with a decreased risk of thyroid cancer. In summary, our findings demonstrate a genetic correlation between COVID-19 and thyroid cancer, contributing to our understanding of the interplay between COVID-19 and cancer risk.

IGFBP2 functions as an endogenous protector against hepatic steatosis via suppression of the EGFR-STAT3 pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is deemed as an emerging global epidemic, whereas the underlying pathogenic mechanism remains to be clarified. We aimed to systemically analyze all the NAFLD-related gene expression datasets from published human-based studies, by which exploring potential key factors and mechanisms accounting for the pathogenesis of NAFLD. METHODS: Robust rank aggregation (RRA) method was used to integrate NAFLD-related gene expression datasets. For fatty liver study, adeno-associated virus (AAV) delivery and genetic knockout mice were used to create IGFBP2 (Insulin-like growth factor binding protein 2) gain- or loss-of function models. Western blot, Co-immunoprecipitation (Co-IP), immunofluorescent (IF) staining, luciferase assay, molecular docking simulation were performed to reveal the IGFBP2-EGFR-STAT3 axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining. RESULTS: By using RRA method, the present study identified IGFBP2 being the most significantly down-regulated gene in all NAFLD subjects. The decreased IGFBP2 expression was further confirmed in the liver tissues from patients and animal models of NAFLD. IGFBP2 deficiency aggravated hepatic steatosis and NASH phenotypes and promoted lipogenic gene expression both in vivo and in vitro. Mechanistically, IGFBP2 directly binds to and regulates EGFR, whereas blockage of the IGFBP2-EGFR complex by knockdown of IGFBP2 resulted in the EGFR-STAT3 pathway activation, which in turn promoted the promoter activity of Srebf1. By using molecular docking simulation and protein-protein interaction analysis, the sequence of 233-257 amino acids in IGFBP2 was characterized as a key motif responding for its specific binding to EGFR and the protective effect against hepatic steatosis. CONCLUSIONS: The current study has, for the first time, identified IGFBP2 as a novel protector against hepatosteatosis. The protective effect is mediated by its specific interaction with EGFR and thereby suppressing the EGFR-STAT3 pathway. Therefore, pharmaceutically targeting the IGFBP2-EGFR-STAT3 axis may provide a theoretical basis for for the treatment of NAFLD/NASH and the associated diseases.

Comparison of robotic or computer-assisted navigation versus fluoroscopic freehand techniques in the accuracy of posterior cervical screw placement during cervical spine surgery: a meta-analysis.

OBJECTIVE: Robot guidance (RG) and computer-assisted navigation (CAN) have been increasingly utilized for posterior cervical screw placement in cervical spine surgery, and cervical screw malposition may contribute to catastrophic complications. However, the superiority of the navigation using RG or CAN compared with conventional freehand (FH) techniques remains controversial, and no meta-analysis comparing the two methods in cervical spine surgery has been performed. METHODS: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure, and Wanfang databases were searched for eligible literature. Studies reporting the primary outcomes of the accuracy of cervical screw placement using RG or CAN compared with FH techniques were included. Bias was evaluated using the Cochrane risk of bias criteria and the Newcastle-Ottawa Scale. The outcomes were evaluated in terms of odds ratio or standardized mean difference and corresponding 95% confidence interval. RESULTS: One randomized controlled trial and 18 comparative cohort studies published between 2012 and 2023 consisting of 946 patients and 4163 cervical screws were included in this meta-analysis. The RG and CAN techniques were associated with a substantially higher rate of optimal and clinically acceptable cervical screw accuracy than FH techniques. Furthermore, compared with the FH group, the navigation group showed fewer postoperative adverse events, less blood loss, shorter hospital lengths of stay, and lower postoperative Neck Disability Index scores. However, the navigation and FH groups had equivalent intraoperative times and postoperative visual analog scale and Japanese Orthopaedic Association scores at the final follow-up. CONCLUSIONS: Both RG and CAN are superior to FH techniques in terms of the accuracy of cervical screw placement. Navigation techniques, including RG and CAN methods, are accurate, safe, and feasible in cervical spine surgery.

Protocatechualdehyde inhibits iron overload-induced bone loss by inhibiting inflammation and oxidative stress in senile rats.

The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown. Therefore, this study aimed to assess the role of PCA in iron overload-induced bone loss in senile rats. In the aged rat model, we observed that iron overload affects bone metabolism and bone remodeling, manifested by bone loss and decreased bone mineral density. The administration of PCA effectively mitigated the detrimental effects caused by iron overload, and concomitant reduction in MDA serum levels and elevation of SOD were noted. In addition, PCA-treated rats were observed to have significantly increased bone mass and elevated expression of SIRT3，BMP2，SOD2 and reduced expression of TNF-α in bone tissue. We also observed that PCA was able to reduce oxidative stress and inflammation and restore the imbalance in bone metabolism. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclasts differentiation, PCA intervention could significantly recover the restriction of osteogenic differentiation and up-regulation of osteoclast differentiation treated by iron overload. Further, by detecting changes in ROS, SOD, MDA, expression of SIRT3 and mitochondrial membrane potentials, we confirm that the damage caused to cells by iron overload is associated with decreased SIRT3 activity, and that 3-TYP have similar effects on oxidative stress caused by FAC. In conclusion, PCA can resist iron overload-induced bone damage by improving SIRT3 activity, anti-inflammatory and anti-oxidative stress.

Guanylate cyclase promotes osseointegration by inhibiting oxidative stress and inflammation in aged rats with iron overload.

Aims: This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods: In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results: Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion: Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing.

Biomechanical changes of oblique lumbar interbody fusion with different fixation techniques in degenerative spondylolisthesis lumbar spine: a finite element analysis.

OBJECTIVE: There is a dearth of comprehensive research on the stability of the spinal biomechanical structure when combining Oblique Lumbar Interbody Fusion (OLIF) with internal fixation methods. Hence, we have devised this experiment to meticulously examine and analyze the biomechanical changes that arise from combining OLIF surgery with different internal fixation techniques in patients diagnosed with degenerative lumbar spondylolisthesis. METHODS: Seven validated finite element models were reconstructed based on computed tomography scan images of the L3-L5 segment. These models included the intact model, a stand-alone (S-A) OLIF model, a lateral screw rod (LSR) OLIF model, a bilateral pedicle screw (BPS) OLIF model, an unilateral pedicle screw (UPS) OLIF model, a bilateral CBT (BCBT) OLIF model, and an unilateral CBT(UCBT) OLIF model. The range of motion (ROM), as well as stress levels in the cage, L4 lower endplate, L5 upper endplate, and fixation constructs were assessed across these different model configurations. RESULTS: S-A model had the highest average ROM of six motion modes, followed by LSR, UPS, UCBT, BPS and BCBT. The BCBT model had a relatively lower cage stress than the others. The maximum peak von Mises stress of the fixation constructs was found in the LSR model. The maximum peak von Mises stress of L4 lower endplate was found in the S-A model. The peak von Mises stress on the L4 lower endplate of the rest surgical models showed no significant difference. The maximum peak von Mises stress of the L5 upper endplate was found in the S-A model. The minimum peak von Mises stress of the L5 upper endplate was found in the BCBT model. No significant difference was found for the peak von Mises stress of the L5 upper endplate among LSR, BPS, UPS and UCBT models. CONCLUSION: Among the six different fixation techniques, BCBT exhibited superior biomechanical stability and minimal stress on the cage-endplate interface. It was followed by BPS, UCBT, UPS, and LSR in terms of effectiveness. Conversely, S-A OLIF demonstrated the least stability and resulted in increased stress on both the cage and endplates. Combining OLIF with BCBT fixation technique enhanced biomechanical stability compared to BPS and presented as a less invasive alternative treatment for patients with degenerative lumbar spondylolisthesis.

Ganoderic Acid A prevents bone loss in lipopolysaccharide-treated male rats by reducing oxidative stress and inflammatory.

Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.

Localized 131 I Uptake in the Deltoid Muscle Bilaterally After Parathyroid Transplantation.

ABSTRACT: A 49-year-old woman patient with thyroid cancer accepted thyroidectomy and parathyroid transplantation. One month later, localized 131 I uptake in the deltoid muscle bilaterally was detected by 131 I whole-body imaging performed in 2 days after 131 I administration.