A novel scoring system for assessing adult syringomyelia associated with CM I treatment outcomes.

BACKGROUND: A specific scoring system for syringomyelia is lacking. Our objective was to investigate the value of a novel scoring system (Syringomyelia Outcome Scale of Xuanwu hospital, SOS-XW) in assessing surgical outcomes in the treatment of syringomyelia (SM) associated with Chiari malformation type I (CM I). METHODS: A quantitative evaluation system (SOS-XW) of SM includes 4 parameters: pain (P), sensation (S), movement (M), and syringomyelia tension index (STI). The clinical data of 88 patients with CM I-related syringomyelia treated by foramen magnum and Magendie dredging (FMMD) from January 2018 to January 2019 were retrospectively analysed with a mean follow-up of 14.3 months, and the SOS-XW score was used to assess the efficacy. RESULTS: The higher the SOS-XW score, the more severe was the SM and related symptoms. The mean preoperative score was 5.97, and the postoperative score was 2.66. The symptom improvement rates were 77.78% for P, 69.01% for S, 31.82% for M, and 95.06% for the syringomyelia tension index (STI). The symptom improvement rate of the PSM score was weakly correlated with the improvement rate of STI, R2 = 0.0016. The percentage of PSM (P + S + M) improvement was lower in patients with an STI of 0. The postoperative SOS-XW score was positively correlated with the postoperative JOA score, R2 = 0.8314. The positive detection rate of SOS-XW was higher than that of the JOA score. CONCLUSIONS: To evaluate the surgical procedure efficacy in the treatment of syringomyelia, the SOS-XW score can provide a more objective, detailed, and comprehensive analysis, especially STI. A reduction in STI is the practical standard for assessing the effectiveness of surgery.

Design, Synthesis and Antitumor Activity of FAK/PLK1 Dual Inhibitors with Quinazolinone as the Skeleton.

Febrifugine is a kind of quinazolinone compound with high biological activity from a Chinese herb called Chang Shan (Dichroa febrifuga). Febrifugine and its derivatives possess extensive biological activities, some of which exhibited anti-tumor activities as FAK inhibitors. However, they are not very effective at inhibiting tumor metastasis, perhaps because tumors gain energy through compensatory activation of other signaling pathways that promote cell migration and invasion. Therefore, seventeen novel febrifugine derivatives with quinazolinone skeleton were designed, synthesized and acted as potential FAK/PLK1 dual inhibitors. These compounds were determined by 1 H-NMR, 13 C-NMR and MS. Most of the compounds exhibited good inhibitory activity against cancer cell lines by computer-assisted screening, antitumor activity test and FAK/PLK1 inhibitory activity test, wherein compound 3b was screened as a high-efficiency lead compound.

Osteoporotic-like vertebral fracture with less than 20% height loss is associated with increased further vertebral fracture risk in older women: the MrOS and MsOS (Hong Kong) year-18 follow-up radiograph results.

Background: For osteoporotic fractures in men (MrOS) and in women (MsOS) (Hong Kong) baseline (BL) study, Chinese men and women ≥65 years were recruited during 2001 to 2003. This study presents the year-18 follow-up (FU) results. We were particularly interested in whether women with 'minimal' grade osteoporotic-like vertebral fracture (OLVF) of <20% height loss have an increased vertebral fracture (VF) risk than those without BL OLVF. Methods: At year-18 FU, spine radiography was performed on 144 males (mean: 87.4±3.1 years) and 156 females (mean: 87.0±3.2 years). OLVF classification included no OLVF (grade 0), and OLVFs with <20%, ≥20-25%, ≥25%-1/3, ≥1/3-40%, ≥40%-2/3, ≥2/3 height loss (grades 1-6). With an existing OLVF, a further height loss of ≥15% was an OLVF progression. A new incident OLVF was a change from grade 0 to ≥ grade 2 or to grade 1 with the appearance of endplate and/or cortex fracture (ECF) during FU. Both OLVF progression and incident OLVF were considered incident VF. Acquired short vertebra (aSV) was defined as with decreased vertebral anterior and middle heights, while without anterior wedging and bi-concave changes, and only those with at least two adjacent aSVs were recorded as aSV cases. Results: For subjects without BL OLVF, 12.5% of the males and 27.1% of the females had incident VF. For subjects with BL OLVF of ≥20% height loss, males' and females' incident VF rate were 20% and 66.7% respectively. Females subjects with BL minimal OLVF, while all without radiographic ECF, had an incident VF rate of 59.3% during the FU. For males with and without aSV, 11.8% and 15% have incident fracture of other vertebrae. For females with and without aSV, 35.3% and 34.5% have incident fracture of other vertebrae. Recovery from minimal or mild grades OLVF to normal shape was observed in a number of cases. Conclusions: OLVF with less than 20% height loss is associated with increased VF risk in older females, but not in older males. Acquired short vertebra (SV) is not associated with increased incident fracture risk for other vertebrae, both for females and males. OLVF among older subjects can repair and heal.

Neurological deterioration after posterior fossa decompression for adult syringomyelia: Proposal for a summarized treatment algorithm.

Background: Patients with syringomyelia who present with new neurological symptoms after posterior fossa decompression (PFD) are not uncommon. However, systematic reports on different pathologies are few in the literature. Objective: The purpose of this study was to summarize our experience for failed PFD. Methods: Between January 2015 and December 2019, 85 consecutive failed PFD patients were identified. The neurological courses were summarized with Klekamp J (KJ) or mJOA score system for all patients. Long-term results were summarized with Kaplan-Meier method. Results: Twenty-eight consecutive patients underwent FMDD (Foramen magnum and foramen of Magendie dredging) (Group I), extradural PFD and manipulation of tonsil was significantly associated with lower failure rates. Twenty patients underwent craniocervical fixation (Group II), nine underwent local spinal segment decompression (Group III), six underwent CSF diversion procedures, and one were treated for persistent pain by radiofrequency. Neuropathic pain was most significantly improved in Group I while swallowing improved in Group II within 1 year after the surgery. In the long term, late postoperative deterioration-free possibility in Group II was better than in Group I. All patients in Group III improved (P = 0.0088). Six cases of CSF diversion procedures were relieved in a short time. Pain in one patient persisted after PFD, and trial of radiofrequency failed. Conclusion: Not only does the recurrent cerebrospinal fluid flow obstruct the foramen magnum, but also spinal pathologies and craniocervical instabilities may occur. This study provides the largest summarized clinical experience that may assist surgeons with different therapeutic decisions for failed PFD.

Spinal Obstruction-Related vs. Craniocervical Junction-Related Syringomyelia: A Comparative Study.

Background: No prior reports have focused on spinal cord injury (SCI) characteristics or inflammation after destruction of the blood-spinal cord barrier by syringomyelia. This study aimed to determine the differences in syringomyelia-related central SCI between craniocervical junction (CCJ) syringomyelia and post-traumatic syringomyelia (PTS) before and after decompression. Methods: In all, 106 CCJ, 26 CCJ revision and 15 PTS patients (mean history of symptoms, 71.5 ± 94.3, 88.9 ± 85.5, and 32.3 ± 48.9 months) between 2015 and 2019 were included. The symptom course was analyzed with the American Spinal Injury Association ASIA and Klekamp-Samii scoring systems, and neurological changes were analyzed by the Kaplan-Meier statistics. The mean follow-up was 20.7 ± 6.2, 21.7 ± 8.8, and 34.8 ± 19.4 months. Results: The interval after injury was longer in the PTS group, but the natural history of syringomyelia was shorter (p = 0.0004 and 0.0173, respectively). The initial symptom was usually paraesthesia (p = 0.258), and the other main symptoms were hypoesthesia (p = 0.006) and abnormal muscle strength (p = 0.004), gait (p < 0.0001), and urination (p < 0.0001). SCI associated with PTS was more severe than that associated with the CCJ (p = 0.003). The cavities in the PTS group were primarily located at the thoracolumbar level, while those in the CCJ group were located at the cervical-thoracic segment at the CCJ. The syrinx/cord ratio of the PTS group was more than 75% (p = 0.009), and the intradural adhesions tended to be more severe (p < 0.0001). However, there were no significant differences in long-term clinical efficacy or peripheral blood inflammation markers (PBIMs) except for the red blood cell (RBC) count (p = 0.042). Conclusion: PTS tends to progress faster than CCJ-related syringomyelia. Except for the RBC count, PBIMs showed no value in distinguishing the two forms of syringomyelia. The predictive value of the neutrophil-to-lymphocyte ratio for syringomyelia-related inflammation was negative except in the acute phase.

Design, Synthesis and Molecular Docking of Novel Quinazolinone Hydrazide Derivatives as EGFR Inhibitors.

A series of novel quinazolinone hydrazide derivatives were designed and synthesized as EGFR inhibitors. The results indicated that most of the aimed compounds had potential anti-tumor cell proliferation and EGFR inhibitory activities. In the comprehensive analysis of all the tested compounds, the target compound 9c showed the best anti-tumor cell proliferation activity, (IC50 =1.31 µM for MCF-7, IC50 =1.89 µM for HepG2, IC50 =2.10 µM for SGC), and IC50 =0.59 µM for the EGFR inhibitory activity. Docking results showed that compound 9c could ideally insert the active site and interact with the critical amino acid residues (Val702, Lys721, Met769, Asp831) in the active site.

Comparison of Clinical Efficacy of Epidural Injection With or Without Steroids in the Treatment of Degenerative Disc Disease: Meta-analysis.

BACKGROUND: Selective nerve root block has been widely used to treat degenerative disc disease (DDD), but no detailed research data is provided to compare the efficacy of epidural injection of anesthetics with or without steroids on the DDD treatment. OBJECTIVES: This study aimed to  provide the first comparison of steroids + local anesthetic (LA) or LA alone for the treatment of DDD. STUDY DESIGN: We systematically searched PubMed, Medline, Embase, and Cochrane. A systemic review and meta-analysis were performed to assess the clinical efficacy of both the steroids + LA group and the LA alone group, and subgroup analysis was also adopted. SETTING: A systematic review and meta-analysis using a random effects model on randomized controlled studies (RCTs). METHODS: After reviewing titles, abstracts, risk of bias, and full texts of 15,889 studies that were chosen following removal of duplicates after the initial database search, finally, 19 RCTs were included. Pain rating, functional score, follow-up period, and other-related data were extracted from these included works, and the effect size and statistical significance were calculated by the random effects model. The quality and level of the derived evidence were assessed by means of the  Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: In terms of the Numeric Rating Scale (NRS-11) and Oswestry Disability Index (ODI) at one year, the combination of steroids + LA was obviously superior to LA. Subgroup analysis suggested that the combination of steroids + LA was more effective than LA alone in regard to the ODI in the lumbar group within 2 years. The opioids intake of patients treated by LA alone was less than that of the steroids + LA group within 3 months, and LA alone was more effective in pain score reduction, with more than 50% within 6 months in the interlaminar injection group. However, the combination of steroids + LA was more effective when alleviating the NRS-11 within 18 months in the caudal injection group. LIMITATIONS: Firstly, this analysis was inconsistent in technique, dosage, injection frequency, and follow-up period of epidural injections. Such differences may compromise the reported efficacy. Secondly, adverse reactions arising out of the 2 groups were not examined in that the included RCTs did not provide the data. Thirdly, different injection methods would compromise the outcomes, and no subgroup analysis was performed on different injection methods. Finally, these included articles that were mainly sourced from Manchikanti's team, and thus biased to some extent. CONCLUSIONS: The addition of steroids to anesthetic injectates was associated with a better NRS-11 and ODI compared with LA alone within one year in patients with DDD. Furthermore, the improvement of the ODI was observed within 2 years in patients with lumbar DDD.

Design, synthesis and bioactivity evaluation of thiazolidinedione derivatives as partial agonists targeting PPARγ.

Thiazolidinedione (TZD) is a novel peroxides proliferator activated receptor γ (PPARγ) agonist with many side effects. Herein, we developed a series of novel TZD analogues as partial agonists targeting PPARγ. The study of anti-hyperglycemic activity and anti-inflammatory activity enabled us to identify a novel compound, 4 g, which quickly recover the blood glucose of mice at the concentration of 100 mg/kg, and show similar anti-inflammatory activity to ibuprofen at the concentration of 20 mg/kg. The competitive binding assay confirmed direct binding of 4 g to the LBD of PPARγ with IC50 being 1790 nM, and dose-dependently increased the transcriptional activity of PPARγ. Besides, through computer-aided drug design software simulation docking, it was found that compound 4 g showed the best binding ability to target protein PPARγ. Furthermore, because of the introduction of benzene containing group at N3 position, the stability of H12 in the active pocket is reduced and the stability of H3 and ß-fold is increased, showing the characteristics of some PPARγ agonists, based on the docking model analysis. Together, these results suggest that 4 g is a promising PPARγ agonist that deserves further investigation.