Clinical Analysis of Microwave Ablation Combined with Decompression and Pedicle Screw Fixation in the Treatment of Spinal Metastases.

OBJECTIVES: There is still controversy over the choice of treatment for end-stage spinal metastases. With the continuous development of microwave technology in spinal tumors, related studies have reported that microwave combined with techniques such as pedicle screw fixation and percutaneous vertebroplasty can achieve the purpose of tumor ablation, relieving spinal cord compression, enhancing spinal stability, effectively relieving pain, and reducing recurrence rates. This study aimed to analyze the effectiveness of microwave ablation combined with decompression and pedicle screw fixation in the palliative management of spinal metastases with pathological fractures. METHODS: This retrospective study enrolled 82 patients with spinal metastases and pathological fractures treated between January 2016 and July 2020, with 44 patients undergoing pedicle screw fixation along with laminectomy (fixation group) and the remaining 38 receiving microwave ablation in addition to the treatment provided to group fixation (MWA group). Before surgery, all patients underwent pain assessment using the visual analogue scale (VAS) and evaluation of spinal cord injury using the Frankel classification. After surgery, the patients' prognoses were assessed using the Tomita score, modified Tokuhashi score system, and progression-free survival. Additionally, we compared operative time and blood loss between the two groups. Survival analysis utilized the Kaplan-Meier method with a log-rank test for group comparisons. Paired t-tests and the Mann-Whitney U test were applied to metric and non-normally distributed data, respectively. Neurological function improvement across groups was evaluated using the χ2 test. RESULTS: All patients were followed up for a median duration of 18 and 20 months in the fixation and MWA groups, respectively, with follow-up periods ranging from 6 to 36 months. Statistically significant reductions in postoperative VAS scores were observed in all patients compared with their preoperative scores. The MWA group exhibited reduced blood loss (t = 2.74, p = 0.01), lower VAS scores at the 1- and 3-month follow-ups (t = 2.34, P = 0.02; t = 2.83, p = 0.006), and longer progression-free survival than the fixation group (p = 0.03). Although the operation times in the MWA group were longer than those in the fixation group, this difference was not statistically significant (t = 6.06, p = 0.12). No statistically significant differences were found regarding improvements in spinal cord function between the two groups (p = 0.77). CONCLUSION: Compared with decompression and pedicle screw fixation for treating spinal metastases with pathological fractures, microwave ablation combined with decompression and pedicle screw fixation showed better outcomes in terms of pain control, longer progression-free survival, and lower blood loss without increasing operative time, which has favorable implications for clinical practice.

Surgery combined with anlotinib for local control of patients with resectable extremity desmoid fibromatosis: a retrospective study.

Background: Desmoid fibromatosis (DF) is a pathological intermediate fibroblastoma that is difficult to control locally due to its invasive nature, especially in the extremities. Although anlotinib demonstrated efficacy in treating DF with tolerable safety, the impact of surgical intervention in conjunction with anlotinib administration on local control in patients with extremity DF remains undetermined. Methods: We conducted a retrospective examination of the clinical medical documentation belonging to patients with resectable DF of the extremities who were treated with surgery between January 2010 and June 2022. The patients were divided into two cohorts: surgery alone cohort and surgery combined with anlotinib group (surgery plus anlotinib cohort), crossover to surgery plus anlotinib cohort was admissible for patients in the surgery alone cohort who experienced disease recurrence postoperatively. Clinical data such as basic information, tumor location, anlotinib toxicity, time to recurrence, surgical complications, follow-up time, visual analogue scale (VAS) score and Musculoskeletal Tumor Society (MSTS) score at the last follow-up were collected. Results: In total, 48 consecutive patients (19 males and 29 females) with resectable DF of the extremities, including 25 patients in the surgery alone cohort, 23 patients in the surgery plus anlotinib cohort, and 10 patients who were transferred from the surgery alone cohort to the surgery plus anlotinib cohort. The VAS score at the last follow-up was 5 (IQR, 3-6) in the surgery alone cohort and 2 (IQR, 1-3) in the surgery plus anlotinib cohort, respectively; the MSTS score at the last follow-up was 19 (IQR, 16.5-24) in the surgery alone cohort and 27 (IQR, 25-28) in the surgery plus anlotinib cohort, respectively; these characteristics were statistically different between the two cohorts. The 3-year recurrence-free survival (RFS) of the surgery alone cohort and the surgery plus anlotinib cohort were 37.7% and 72.6%, respectively, and the difference was statistically significant (p = 0.022). Conclusion: Surgery combined with anlotinib appears to be effective in controlling local recurrence in patients with resectable DF of the extremities, and the side effects were acceptable.

Efficacy and safety of tranexamic acid in unicompartmental knee arthroplasty: A systematic review and meta-analysis.

This meta-analysis aimed to assess whether administration tranexamic acid (TXA) could reduce blood loss and vascular events in patients undergoing unicompartmental knee arthroplasty (UKA). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and case control trials (CCT) that compared outcomes of patients who did and did not receive TXA during UKA. We searched Cochrane Central Register of including PubMed, EMBASE, Web of Science, the Cochrane Library, Wan Fang data, CBM and CNKI for relevant studies. We assessed the risk of bias of the included studies and calculated pooled risk estimates. The primary outcome was operation time, intraoperative blood loss, postoperative HCT, postoperative HB, transfusion rate, dominant blood loss, postoperative drainage volume, hidden blood loss, total blood loss, postoperative ROM,postoperative VAS score, postoperative complications. Data were using fixed-effects or random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Finally, 9 clinical studies with 744 patients were included in this meta-analysis. Compared with the control group, TXA group could reduced transfusion rate, dominant blood loss, postoperative drainage volume, hidden blood loss, and total blood loss, and increased postoperative HB with statistically significance. The main findings of this meta-analysis are that the transfusion rate, dominant blood loss, postoperative drainage volume, hidden blood loss, total blood loss and postoperative HB in the tranexamic acid group were superior to those in the routine group. Additional high-quality RCTs should be conducted in the future.

Case Report: Three-dimensional printed prosthesis reconstruction for patello-femoral large osteochondral defects in a patient with distal femoral giant cell tumour: A case report.

Background: The restoration and reconstruction of patello-femoral large osteochondral defects caused by bone tumours are challenging because of the local recurrence rate and the joint's mechanical complexity. Although three-dimensional (3D)-printed prostheses are commonly adopted for tumour-induced bone defect reconstruction, patello-femoral osteochondral reconstruction with 3D-printed prostheses is rarely reported. Case presentation: A 44-year-old female patient with progressive swelling and pain in the left knee for 6 months was diagnosed with Campanacci Grade II giant cell tumour (GCT). She underwent intralesional curettage combined with autografting and internal fixation, after which complications of deep infection arose. The patient then underwent internal fixation removal and cement packing. Afterwards, the pain of the affected knee persisted for 11 months, and bone cement removal plus 3D-printed modular prosthesis reconstruction was performed. At the last follow-up 27 months after surgery, she was pain free, the Musculoskeletal Tumour Society (MSTS) score improved from 15/30 to 29/30, the Visual Analogue Scale (VAS) score decreased from 7 to 0, and knee flexion increased from 50° to 130°. X-ray images 22 months after surgery showed that the prosthesis and screws were in a stable position, and callus formation was found at the prosthesis-bone interface. Conclusions: A 3D-printed modular prosthesis may be a useful treatment option for the surgical reconstruction of GCT-induced patello-femoral large osteochondral defects. The firm fixation, osseointegration, and favourable congruency of the 3D-printed prosthesis with the adjacent articular surface can achieve long-term knee function and stability.

lncRNA OR3A4 Promotes the Proliferation and Metastasis of Ovarian Cancer Through KLF6 Pathway.

Aim: Ovarian cancer is a collaborative malignant tumor of the female reproductive system in clinical research. Some clinical studies have shown that OR3A4, which is a cancer-causing lncRNA, plays a major role in promoting the occurrence and development of a variety of tumors. And we also expressed the view that it expressed in ovarian tissue. However, the function of OR3A4 in ovarian cancer remains unclear. Methods and Results: To further verify the function of lncRNA OR3A4 in ovarian cancer, we established the xenograft model in the zebra fish. In this study, cells transformed with OR3A4 shRNA plasmids were transplanted into the zebra fish, and the cell proliferation and migration ability were significantly reduced compared to the empty vector. While knocking out OR3A4, we further downregulated its expression by siRNA of KLF6. Our study found that the knocked out OR3A4 resulted in a decrease in cell proliferation and migration level, which can be found in the downregulated expression of KLF6. We also verify the relationship between OR3A4 and circulating tumor cells in the zebra fish xenograft model, the results indicate that lncRNA OR3A4 may be involved in the resistance of ovarian cancer to complain. Conclusion: lncRNA OR3A4 promotes the proliferation and metastasis of ovarian cancer through the KLF6 pathway.

Design, synthesis and biological evaluation of novel pyxinol derivatives with anti-heart failure activity.

Heart failure (HF) is an important and leading cause of substantial morbidity and mortality globally. The angiotensin-converting enzymatic (ACE) is the causative source for congestive heart failure. Natural products and its derivatives play a vital role in drug discovery and development owing to their efficacy and low toxicity. Pyxinol is a potent natural agent for cardiovascular disease. Thus we investigated the effect on ACE and HF of pyxinol derivatives. We designed and synthesized 32 novel fatty acid ester derivatives of pyxinol via esterification. Among them, compounds 2e (IC50=105 nM) and 3b (IC50=114 nM) displayed excellent ACE inhibitory activity in vitro, and exhibited non-toxic to H9c2 cells. The interactions between ACE and compounds were predicted by molecular docking respectively. In verapamil-induced zebrafish HF model, the activity assay showed that these two derivatives could improve cardiovascular physiological indexes including heart beats, venous congestion, heart dilation, cardiac output, ejection fraction and fractional shortening in a dose-dependent manner. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 25 differentiated metabolites and 8 perturbed metabolic pathways were identified. These results indicated that pyxinol fatty acid ester derivatives 2e and 3b might be considered as potent drug candidates against heart failure and deserved further research and development.

Protective Effect of Metformin on Sepsis Myocarditis in Zebrafish.

PURPOSE: We found in previous study that metformin could treat sepsis myocarditis in a mouse model. We employed the zebrafish model organism to investigate the effect of metformin on sepsis myocarditis. METHODS AND RESULTS: Wild-type zebrafish was used to establish a sepsis myocarditis model and combined with image software analysis and cytokine detection, the protective dose of metformin was determined. The results showed that immersion with Escherichia coli could cause 75% mortality in zebrafish and make larvae appear as characteristics of severe sepsis myocarditis. Pretreatment with 10 mM metformin for 3 hours could effectively reduce heart congestion and swelling in zebrafish with sepsis myocarditis and increased the heart rate. It could reduce the mortality and prolong the survival time of zebrafish with sepsis myocarditis; Tg(mpx: EGFP) transgenic zebrafish were adopted to explore the number of neutrophils in zebrafish heart before and after metformin protection, and metformin could maintain the number of neutrophils in zebrafish heart; quantitative real-time reverse transcription-polymerase chain reaction showed that metformin could reduce the expression of pro-inflammatory factors, tumor necrosis factor-α and interleukin (IL)-6, and could promote the anti-inflammatory factor, transforming growth factor-ß and IL-10 expression. CONCLUSION: We established a zebrafish sepsis myocarditis model and applied metformin in advance to provide a protective effect on the zebrafish heart.

Construction of irf4a Transgenic Zebrafish Using Tol2 System and Its Potential Application.

PURPOSE: Interferon regulatory factor 4 (IRF4) is identified as a transcriptional factor and plays an important role in the immune response in mammals; however, there are few reports about the function of zebrafish IRF4. METHODS: We first amplified the coding sequence of irf4a from the testis of zebrafish. Besides, the fragments of irf4a, P2A, EGFP, and Tol2 vector were added for homologous recombination. By sequencing, we can get the Tol2-ef1α-irf4a-EGFP recombinant plasmid and it was microinjected into zebrafish embryos. Fluorescence observation was proceeded at days 3 post fertilization; F0 generations expressing green fluorescence in multiple tissues throughout the body were screened as the founder and raised them to sexual maturity. After mating with WT zebrafish to generate F1 offspring, polymerase chain reaction was used to identify whether irf4a was integrated into the zebrafish genome. CONCLUSION: We obtained the systematic overexpressed irf4a transgenic zebrafish with green fluorescence labeled in spine, eyes, heart, brain, and other tissues. The transgenic zebrafish will be used as a tool for the role of IRF4a in the immune response to the inflammation preconditioning in the future study.

Membrane TLR9 Positive Neutrophil Mediated MPLA Protects Against Fatal Bacterial Sepsis.

Sepsis is a major cause of patient mortality and morbidity from bacterial infections. Although neutrophils are known to be important in the development of sepsis, how distinctive neutrophil subtypes regulate inflammatory processes involved in septicemia remains unclear. Preconditioning protects organisms against subsequent higher-dose exposures to the same, or even different, stimuli. Several studies have reported various effects of preconditioning on immune cells. However, the detailed mechanisms underlying neutrophil-mediated protection through preconditioning in sepsis remain unknown. Methods: Flow cytometry was conducted to sort the mice peritoneal lavage cells and the blood samples from patients with sepsis. Western blotting and ELISA were carried out to elucidate the expression of TLR9 signal transduction pathway proteins. Histological analysis was used to assess the effect of InP on intestine and liver structure in tlr9-/- and cav-1-/- mice. Fluorescence microscopy, Co-IP, and FRET were carried out to determine the association of TLR9 with Cav-1. Results: We show that membrane toll-like receptor-9 positive (mTLR9+) neutrophils exert a protective effect against fatal bacterial infections through the process of inflammatory preconditioning (InP). InP, which occurs in the setting of a low-dose bacterial challenge, active ingredient is Monophosphoryl lipid A (MPLA), triggers the membrane translocation of TLR9 from the neutrophil cytosol, where it binds to Cav-1. Our findings showed that InP enables TLR9 to facilitate MyD88-mediated TRAF3 and IRF3 signal transduction. Depletion of either TLR9 or Cav-1 largely eliminates the neutrophil-mediated InP effect in sepsis models in vitro and in vivo. Further, examination of clinical samples from patients with sepsis showed that clinical outcomes and likelihood of recovery are closely correlated with mTLR9 and Cav-1 expression in circulating neutrophils. Conclusion: These results demonstrate that the TLR9-Cav-1 axis is a critical signaling pathway involved in the regulation of neutrophil-dependent MPLA mediated InP, and the presence of mTLR9+ neutrophils could be an attractive indicator of clinical outcomes in bacterial sepsis that could be further explored as a potential therapeutic target.

Mechanism of Metformin on LPS-Induced Bacterial Myocarditis.

AIMS: Metformin is commonly used to treat type 2 diabetes mellitus; however, in recent years, it was found to play a potential role in the protection of myocardial injury. In this study, we intended to investigate whether metformin had protective effects on bacterial myocarditis. METHODS AND RESULTS: We stimulated rat cardiac myoblast H9c2 cells with lipopolysaccharide (LPS) and administrated with metformin. The results showed that cell viability after LPS stimulation was greatly reduced. The expression levels of phosphorylated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinases (JNK), nuclear factor (NF)-κB (NF-κB), BAX, and cleaved Caspase3 were significantly increased, while the expression of antiapoptotic protein Bcl-2 showed a prominent decrease compared to control. Nevertheless, the cells activity increased remarkably after metformin administration, and the expression levels of intracellular related proteins showed the opposite trend to that of the LPS group. CONCLUSION: We demonstrate that LPS stimulation may activate intracellular MAPK/JNK and NF-κB signaling pathways and thus induce cell apoptosis. In contrast, metformin reduced apoptosis by inhibiting this signaling pathway and increasing the expression level of Bcl-2. Moreover, it was found that metformin could enhance the ability of cells to antagonize redox damage by regulating the activities of superoxide dismutase and lactate dehydrogenase and subsequently promote the recovery of cardiomyocyte function.