Fusobacterium nucleatum induces oxaliplatin resistance by inhibiting ferroptosis through E-cadherin/ß-catenin/GPX4 axis in colorectal cancer.

Fusobacterium (F.) nucleatum is a carcinogenesis microbiota in colorectal cancer (CRC). Growing evidence shows that F. nucleatum contributes to chemoresistance. Ferroptosis is reported to restore the susceptibility of resistant cells to chemotherapy. However, the role of gut microbiota affecting ferroptosis in chemoresistance remains unclear. Here, we examined the CRC tissues of patients using 16S rRNA sequencing to investigate the possible connection between gut microbiota dysbiosis and the relapse of CRC. We found that a high abundance of F. nucleatum in CRC tissue is associated with relapse. We further demonstrated that F. nucleatum induced oxaliplatin resistance in vitro and in vivo. The transcriptome of an F. nucleatum-infected cell revealed ferroptosis was associated with F. nucleatum infection. We perform malondialdehyde, ferrous iron, and glutathione assays to verify the effect of F. nucleatum on ferroptosis under oxaliplatin treatment in vivo and in vitro. Mechanistically, F. nucleatum promoted oxaliplatin resistance by overexpressing GPX4 and then inhibiting ferroptosis. E-cadherin/ß-catenin/TCF4 pathway conducted the GPX4 overexpression effect of F. nucleatum. The chromatin immuno-precipitation quantitative PCR (CHIP-qPCR) and dual-luciferase reporter assay showed that F. nucleatum promoted TCF4 binding with GPX4. We also determined the E-cadherin/ß-catenin/TCF4/GPX4 axis related to tumor tissue F. nucleatum status and CRC relapse clinically. Here, we revealed the contribution of F. nucleatum to oxaliplatin resistance by inhibiting ferroptosis in CRC. Targeting F. nucleatum and ferroptosis will provide valuable insight into chemoresistance management and may improve outcomes for patients with CRC.

Design and mechanical properties of cervical fusion cage based on porous entangled metal rubber material.

Titanium and its alloys are one of the mainstream materials for the manufacture of intervertebral cages. With the application on clinical, the problems of elastic modulus is relatively high, subsidence of adjacent vertebral implants and stress shielding after surgery have gradually exposed. In this paper, metal rubber made from titanium alloy wire was used to prepare cervical fusion cage (CFC), which was a porous material with buffering and vibration damping properties. The C5/C6 segment of the goat cervical vertebra was used as the research object. The shape parameters of the CFC were determined by combining the three-dimensional model data of the cervical vertebra and the structural characteristics of the natural intervertebral disc. The force of CFC under different working conditions were simulated and analyzed by finite element simulation. Then three kinds of metal rubber core (MRC) were prepared by medical titanium alloy wire (TC4), and their mechanical properties and fatigue strength were experimentally studied. With the increases of density, the mechanical properties of MRC improved. The variation range of the loss factor η under different amplitudes and frequencies were 20% and 16.3%, respectively. After one million vibrations, the wear rate was 0.131 g/MC; after five million vibrations, the wear rate was 0.158 g/MC, which was similar to the existing clinical prosthesis wear rate. The MRC has sufficient mechanical strength. Compared with the existing clinical prostheses, it has a longer service life and has broad application prospects.

Factors Associated with Shoulder Range of Motion After Arthroscopic Rotator Cuff Repair: A Hospital-Based Prospective Study.

OBJECTIVE: To assess the factors associated with outcomes of arthroscopic surgical repair of rotator cuff tears (RCTs). METHOD: This prospective study recruited patients, at least 18 years old, who underwent arthroscopic rotator cuff repair for full-thickness RCTs at the First People's Hospital of Hangzhou Xiaoshan between July 2019 and October 2020. Patient demographics, lifestyle habits, and medical histories were collected preoperatively; RCT sizes and affected tendons were determined intraoperatively. Outcomes were assessed by shoulder range of motion (ROM) determinations 1.5 and 3 months postoperatively. The factors associated with ROM were determined using a binary logistic regression analysis, and the results were expressed as adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 132 patients with RCTs underwent arthroscopic surgery. Five were lost to follow-up, leaving 127 patients (mean age, 59 years; 58.3% women) who were included in the study analysis. The majority of the patients (54.5%) had RCTs that were classified as large or massive, and approximately 20% had tears involving multiple tendons; 80.3% of the patients had tears involving only a single tendon. Moreover, 29.9% of the patients had hypertension and 11.0% had diabetes. Among the patients, 23.0% were smokers and 34.6% drank alcohol. According to the multivariate analysis, none of the assessed factors were associated with shoulder ROM at the 1.5-month follow-up. At the 3-month follow-up, RCTs involving a single tendon demonstrated 3-fold better abduction (RR = 4.00; 95% CI, 1.30-12.33; P = 0.016) and 3.15-fold better internal rotation (RR = 3.15; 95% CI, 1.19-8.36; P = 0.021) than did RCTs involving multiple tendons. Patients who did not drink alcohol demonstrated 6.08-fold better anteflexion (RR = 7.08; 95% CI, 2.11-23.73; P = 0.002) and nearly 4-fold better abduction (RR = 4.97; 95% CI, 1.62-15.23; P = 0.005) than patients who drank alcohol. CONCLUSION: To improve outcomes, the results indicate that more targeted measures should be directed toward patients with multiple-tendon RCTs and that preoperative alcohol abstinence education is needed for patients with RCTs.

Comparison of surface properties, cell behaviors, bone regeneration and osseointegration between nano tantalum/PEEK composite and nano silicon nitride/PEEK composite.

Both tantalum (Ta) and silicon nitride (SN) exhibit osteogenic bioactivity and antibacterial property. In addition, as a biomaterial for bone repair, polyetheretherketone (PEEK) has outstanding biocompatibility and mechanical performances while it is biologically inert. In this study, by blending PEEK with Ta and SN nanoparticles, respectively, Ta/PEEK composite (TPC) and SN/PEEK composite (SPC) were fabricated for load-bearing bone repair. The surface roughness, hydrophilicity and surface energy of TPC containing Ta nanoparticles were higher than SPC containing SN nanoparticles and PEEK. In addition, TPC with Ta nanoparticles exhibited low antibacterial property while SPC with SN nanoparticles showed high bacterial property. Moreover, the MC3T3-E1 cells responses (e.g. proliferation and differentiation) to TPC was the highest while PEEK was the lowest in vitro. Furthermore, new bone formation and osseointegration for TPC was the highest while PEEK was the lowest in vivo. In conclusion, compared with PEEK, addition of Ta and SN nanoparticles into PEEK fabricated bioactive composites of TPC and SPC with optimized surface property, which played crucial roles in inducing cellular response/bone regeneration. Although the osteogenic activity of SPC was lower than TPC, SPC exhibited osteogenic activity and good antibacterial property, which could prevent infection from bacterial. Therefore, SPC would have better potential for bone substitute.