ABSTRACT
Objective@#To compare the clinical effects between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) assisted by Microendoscopic discectomy (MED) and Quadrant for the treatment of degenerative lumbar spinal stenosis (DLSS).@*Methods@#All of 59 patients suffered from DLSS treated surgically from May 2015 to October 2017 were reviewed. According to the surgery method, all cases were divided into MED group (27 cases) and Quadrant channel group (32 cases). All patients were followed up for an average of 18.5 months (11-29 months). Comparison was made on the operative time, intraoperative blood loss, postoperative drainage, postoperative time in bed, postoperative creatine kinase (CK), fusion rate and the degree of muscle fibrosis shown in MRI, as well as visual analogue scale (VAS)score and Oswestry dysfunction index (ODI) score in two groups.@*Results@#The duration of operation in MED group was significantly longer than that in Quadrant group (161.7±22.4 min vs. 145.6±19.4 min, t=4.541, P<0. 01), but less intraoperative blood loss (138.1±26.9 ml vs. 155.6±21.5 ml, t=-2.724, P< 0. 01) and shorter time in bed after surgery (2.3±0.7 d vs. 3.5±1.1 d, t=-4.564, P<0.01). Compared with Quadrant group, CK levels were risen slightly on the first and third postoperative day (P<0.01). CK on the fifth postoperative day in both groups returned to normal. VAS score of lower back pain in MED group was lower than that in Quadrant group on the third day and twelfth month after operation (P<0.05). After 3 months, there was no significant difference in VAS score and ODI between the two groups (P>0.05). ODI was lower in MED group than that in Quadrant group after 6 months and 12 months.The fusion rate was88.9%(24/27) in MED group and 93.8%(30/32) in Quadrant channel group. There was no statistical difference in fusion rate of two groups. 10 patients in MED group and 12 patients in Quadrant group underwent MRI examination of lumbar spine one year after operation. The ratio of postoperative and preoperative atrophy of multiplex muscle area was measured. Muscle atrophy of lower back muscle was lighter in MED group (0.12±0.05 vs. 0.22±0.04, t=-2.428, P<0.05). For intraoperative and postoperative complications, 1 case of dural sac rupture occurred in both groups. Gelatin sponge immediately with fibrin glue was used for plugging up, no postoperative cerebrospinal fluid leakage was found. In Quadrant channel group, 1 case had less blood supply of skin incision edges and epidermal necrosis while the other case had fat liquefaction.@*Conclusion@#Compared with the aid of Quadrant, MIS-TLIF assisted with MED had less blood loss, less trauma and faster recovery and could reduce the incidence of postoperative incision complication.
ABSTRACT
Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.