The amphiphilic block copolymers methoxy poly(ethylene glycol)-poly(ε-caprolactone) was grafted to 2-hydroxyethyl cellulose to produce the water-soluble copolymers. Doxorubicin loaded nanoparticles were prepared by dialysis method and the sizes of nanoparticles were determined by dynamic light scattering in solution and atomic force microscopes. As results the sizes were detected in a range of 197.4 to 340.7 nm. The in-vitro release of Dox was studied in phosphate and acetate buffered solution at 37 °C. The results showed that 43 and 53% of Dox remained after an incubation period of 7 days. The cytotoxicity of Dox loaded micelles was investigated in two different human MCF-7/wild type and MCF-7/Adriamycin drug resistant cells lines. The Dox-loaded micelles showed reduced cytotoxicity compared to free Dox in MCF-7/wild type and MCF-7/Adriamycin drug resistant cells.

This study aimed to compare the differences in radiological outcomes and complications between single- and multilevel anterior cervical discectomy and fusion (ACDF) by using a polyetheretherketone (PEEK) cage–plate fusion system. Fifty-seven patients who underwent ACDF via the PEEK cage–plate fusion system were enrolled and subjected to ≥6 months of follow-up. The patients were divided into 4 groups according to different cage–plate implantation levels: 1-level group (n = 17), 2-level group (n = 24), 3-level group (n = 12), and 4-level group (n = 4). Fusion time, changes in segment and global lordotic angle, subsidence rate, and changes in disc and adjacent segmental disc height were subjected to radiological evaluation. The fusion period of multilevel ACDF was longer than that of single-level ACDF. The fusion period of the 3-level (4.09 ± 0.94, P = .004) and 4-level (5.25 ± 0.89, P = .004) group was also significantly longer than that of the 1-level group. The mean lordotic angle in all of the groups was changed in the immediate postoperative period and in the final follow-up. The cage subsidence rates were 11.76% (2/17) in the 1-level group, 20.83% (5/24) in the 2-level group, and 2/12 (16.67%) in the 3-level group. No subsidence occurred in the 4-level groups. Changes in the lower adjacent segmental disc height were significantly increased in multilevel ACDF compared with those in single-level ACDF. Despite the longer fusion time, the outcomes of the proposed system were even better with the greater number of treatment levels by using PEEK cage–plate fusion system. Changes in the lower adjacent segmental disc height should also prolong follow-up duration to investigate the symptomatic adjacent segment degeneration in multilevel ACDF.

Vitamin C and vitamin E are well‐known antioxidant vitamins, both of which are also applied as adjunct treatments for cancer therapy. Methotrexate (MTX) is a clinical drug that is used widely for rheumatoid arthritis and cancer treatment. Human glioblastoma multiforme (GBM) is an aggressive malignant brain tumor; the mean survival time for GBM patients is <2 years with traditional therapies. Developing and investigating novel treatments are important for clinical GBM therapy. Therefore, the aim of this study was to investigate whether combined treatment with vitamin C/E and MTX can display anticancer activities on GBM. Our studies showed that MTX displays anticancer effects on GBM in a dose‐dependent manner, while vitamins C and E are not cytotoxic to glioblastoma. Importantly, this study showed that vitamins C and E can promote anticancer effects on low‐concentration methotrexate‐treated glioblastoma. Additionally, this study suggested that MTX alone or combined with vitamins C/E inhibits GBM cell growth via the caspase‐3 death pathway.

This study aimed to verify the relationship between the number of fusion level and the risk of screw loosening by using cortical bone trajectory (CBT) screws in patients with lumbar degenerative disease. We retrospectively reviewed the serial plain radiograph images of lumbar degenerative disease patients who had undergone posterior fixation and fusion surgery with CBT from 2014. All included patients should have been followed-up with computed tomography scan or plain radiograph for at least 6 months after operation. We individually evaluated the prevalence of screw loosening according to each vertebral level. We also determined whether the number of screw fixation affected the prevalence of screw loosening and whether S1 fixation increased the risk of screw loosening. The screw-loosening rates were high at the S1 level. Moreover, although fixation involved to S1, the loosening rates evidently increased (Fisher exact test, P = .002 ∗∗ ). The screw-loosening rate was 6.56% in 2 level fusion. However, it increased with the number of fusion levels (3 level: 25.00%, 4 level: 51.16%, and 5 level: 62.50%). To investigate if the number of fusion level affected the S1 screw loosening, we classified the cohort of patients into either involving S1 (S1+ group) or not (S1– group) according to different fusion levels (Table 3 ). The screw loosening between 2 group in 2 (5.56% vs 6.98%) and 3 fusion level (26.32% vs 22.73%) did not exhibit any significant difference. Interestingly, significantly high screw loosening was found in 4 fusion level (60.00% vs 15.38%), indicating that the higher fusion level (4 level) can directly increase the risk of S1 screw loosening. Our data confirmed that the screw-loosening rate increases rate when long segment CBT fixation involves to S1. Therefore, in case of long-segment fixation by using CBT screw, surgeons should be aware of the fusion level of S1.

The amphiphilic block copolymers methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) was grafted to 2-hydroxyethyl cellulose to produce the water-soluble copolymers. Doxorubicin loaded nanoparticles were prepared by dialysis method and the sizes of nanoparticles were determined by dynamic light scattering in solution and atomic force microscopes. As results the sizes were detected in a range of 197.4 to 340.7 nm. The in-vitro release of Dox was studied in phosphate and acetate buffered solution at 37 degrees C. The results showed that 43 and 53% of Dox remained after an incubation period of 7 days. The cytotoxicity of Dox loaded micelles was investigated in two different human MCF-7/wild type and MCF-7/Adriamycin drug resistant cells lines. The Dox-loaded micelles showed reduced cytotoxicity compared to free Dox in MCF-7/wild type and MCF-7/Adriamycin drug resistant cells.

Purpose: This study aims to elucidate the radiological outcome after Cortical bone trajectory (CBT) screw fixation and whether dual-threaded (DT) screws should be used in the fusion surgery. Methods: 159 patients with degenerative lumbar disorder who had undergone midline lumbar inter-body fusion surgery by CBT screw-fixation technique (2014 to 2018). Patient subgroups were based on single-threaded (ST) or DT screw, fixation length, as well as whether fixation involved to sacrum level (S1). Serial dynamic plain films were reviewed and an appearance of a halo phenomenon between screw–bone interfaces was identified as a case of screw loosening. Results: 29 patients (39.7%) in ST group and 10 patients (11.6%) in DT group demonstrated a halo phenomenon (p < 0.0001 ****). After subgrouping with fixation length, the incidence rates of a halo phenomenon in each group were 11.1%:3% (ST-1L vs. DT-1L), 37%:13.8% (ST-2L vs. DT-2L), and 84.2%:23.5% (ST-3L vs. DT-3L). Among the 85 patients with a fixation involved in S1, 26 patients (52%) with single-threaded screw (STS group) and 8 patients (22.8%) with dual-threaded screw (DTS group) demonstrated a halo appearance (p = 0.0078 **). After subgrouping the fixation level, the incidence of a halo appearance in each group was 25%:0% (STS-1L vs. DTS-1L), 40.9%:26.3% (STS-2L vs. DTS-2L), and 87.5%: 30% (STS-3L vs. DTS-3L). Conclusion: Both fixation length and whether fixation involved to S1 contribute to the incidence of screw loosening, the data supports clinical evidence that DT screws had greater fixation strength with an increased fixative stability and lower incidence of screw loosening in CBT screw fixation compared with ST screws. Level of evidence: 2.

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Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells&rsquo; resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-&beta;1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.