Learning curve of junior surgeons in robot-assisted pedicle screw placement: a comparative cohort study.

OBJECTIVE: Robot-assisted technology has been gradually applied to pedicle screw placement in spinal surgery. This study was designed to detailedly evaluate the learning curve of junior surgeons in robot-assisted spine surgery. METHODS: From December 2020 to February 2022, 199 patients requiring surgical treatment with posterior pedicle screw fixation were prospectively recruited into the study. The patients were randomized to the robot-assisted group (the RA group) or the conventional freehand group (the CF group). Under the senior specialist's supervision, pedicle screws were placed by two junior fellows without prior experience. Cumulative summation (CUSUM) analysis was performed on the learning curve of pedicle screw placement for performing quantitative assessment based on the time of screw insertion. RESULTS: In total, 769 and 788 pedicle screws were placed in the RA and CF groups. Compared with the CF group, the learning duration in the RA group was shorter in the upper thoracic region (57 vs. 70 screws), but longer in the lower thoracic (62 vs. 58 screws) and the lumbosacral region (56 vs. 48 screws). The slope of learning curve was lower in the RA group than in the CF group. The screw accuracy in the RA group was superior to that in the CF group, especially in upper thoracic region (89.4% vs. 76.7%, P < 0.001). This disparity of accuracy became wider in deformity cases. In the upper thoracic region, the mean placement time was 5.34 ± 1.96 min in the RA group and 5.52 ± 2.43 min in the CF groups, while in the lower thoracic and lumbosacral regions, the CF group's mean placement times were statistically shorter. Three screw-related neural complications occurred in the CF group. CONCLUSION: Robot-assisted technique has its advantages in the upper thoracic region and deformity cases, which is easier and safer to insert pedicle screws. The robot-assisted technique allowed a short learning curve for junior surgeons and exhibited consistently excellent results even in the early application period.

Multifunctional properties of the transmembrane LPxTG-motif protein derived from Limosilactobacillus reuteri SH-23.

The LPxTG-motif protein is an important transmembrane protein with high hydrophilicity and stability, as evidenced by its stress tolerance and adhesion ability. In this study, a novel LPxTG-motif protein with esterase activity (LEP) was expressed, and the multifunctional properties such as adhesion properties and esterase activity were also investigated. When cocultured with Limosilactobacillus reuteri SH-23, the adhesion ability of L. reuteri SH-23 to HT-29 cells was improved, and this adhesion was further found relating to the potential target protein Pyruvate kinase M1/2 (PKM) of HT-29 cells. In addition, as a multifunctional protein, LEP can promote the hydrolysis of bovine milk lipids with its esterase activity, and the activity was enhanced in the presence of Zn2+ and Mn2+ at pH 7. Furthermore, the polyunsaturated fatty acids (PUFA) such as linoleic acid and eicosapentaenoic acid were found to increase during the hydrolyzing process. These unique properties of LEP provide a comprehensive understanding of the adhesion function and PUFA releasing properties of the multifunctional protein derived from L. reuteri SH-23 and shed light on the beneficial effect of this Lactobacillus strain on the colonization of the gastrointestinal tract.

[Application of 3D printing percutaneous guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture].

OBJECTIVE: To investigate the application of 3D printing percutaneous surgical guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture. METHODS: The clinical data of 12 patients with femoral neck fracture from March 2019 to March 2022 were retrospectively analyzed. Patients were divided into observation group and control group according to different operation plans, with 6 cases in each group. The observation group received percutaneous operation guide plate assisted closed reduction and hollow screw internal fixation, while the control group received closed reduction and hollow compression screw internal fixation. The operation time, intraoperative blood loss, fluoroscopy times, and Kirschner needle puncture times were compared between two groups. The location of screws were recordedon postoperative X-ray films, follow-up time, time of complete fracture healing, Harris score of hip joint and the incidence of complications were recorded on postoperative X-ray films. RESULTS: The operation time of observation group (32.17±6.18) min was shorter than that of control group (53.83±7.31) min (P<0.05). The amount of intraoperative bleeding in the observation group (18.33±2.94) ml was less than that in the control group (38.17±5.56) ml(P<0.05). The times of fluoroscopy in the observation group (7.50±1.05) were less than those in the control group (21.00±4.82) (P<0.05). The number of Kirschner needle punctures (8.00±0.63) in observation group was less than that in control group (32.67±3.08) (P<0.05). The follow-up time was(12.88±0.74) months in observation group and (12.83±0.72) months in control group, there was no significant difference between two groups (P>0.05). One year after operation, Harris score of hip joint in the observation group was(82.00±4.52) points, while that in the control group was(81.00±3.41) points, there was no significant difference between two groups(P>0.05). The time of complete fracture healing in the observation group was (7.50±1.05) months, while that in the control group was (7.67±1.21) months, there was no significant difference between two groups(P>0.05). The parallelism of the screws in the observation group was (0.50±0.11) ° and (0.76±0.15) °, which were lower than that in the control group (1.57±0.31) ° and (1.87±0.21) ° (P<0.05). The screw distribution area ratio (0.13±0.02) cm2 in the observation group was higher than that in the control group (0.08±0.01) cm2 (P<0.05). No complications such as necrosis of femoral head, nonunion of fracture, shortening of femoral neck and withdrawal of internal fixation occurred in both groups. CONCLUSION: The application of 3D printing percutaneous surgical guide plate improves the accuracy and safety of closed reduction and cannulated screw internal fixation for femoral neck fracture. It has the advantages of minimally invasive, reducing radiation exposure, fast and accurate, shortening the operation time and reducing intraoperative bleeding.

Plant-based meat analogue of soy proteins by the multi-strain solid-state mixing fermentation.

In order to mitigate or reduce global environmental concerns, health issues, sustainability and animal welfare issues, artificial meat presents a potential solution to consumers' demand for meat. In this study, strains such as Rhodotorula mucilaginosa and Monascus purpureus that can produce meat-like pigments were first identified and used in soy protein plant-base fermentation, where fermentation parameters as well as inoculum size were determined to simulate plant-base meat analogue (PBMA). Meanwhile, the resemblance between the fermented soy products and the fresh meat was examined in terms of color, texture, and flavor characteristics. Furthermore, the addition of Lactiplantibacillus plantarum can perform reassortment and fermentation simultaneously to improve the quality of soy fermentation products in terms of texture and flavor. The results offer a novel way to produce PBMA and also shed light on future research into plant-based meat-like products with the appropriate meat characteristics.

Anti-inflammation and gut microbiota regulation properties of fatty acids derived from fermented milk in mice with dextran sulfate sodium-induced colitis.

The by-products of milk fermentation by lactic acid bacteria provide potential health benefits to the balance of host intestinal microflora. In this study, the anti-inflammatory properties of fatty acids from monoculture-strain (Lactiplantibacillusplantarum A3) and multiple-strain (Streptococcus thermophilus, Lactobacillus bulgaricus, and L. plantarum A3 1:1:2) fermented milk were evaluated in a mouse model of dextran sulfate sodium-induced colitis, and the gut microbiota regulation properties of the fatty acids were also investigated. Results showed that fatty acids can attenuate the inflammatory response by inhibiting the expression of inflammatory factors IL-6 and tumor necrosis factor-α, and blocking the phosphorylation of the JNK in MAPK signal pathway. In addition, the relative abundance of the taxa Akkermansia and Lactobacillus were both enriched after the fatty acid intervention. This finding suggests that fatty acids from the milk fermentation with mixed lactic acid bacteria starters can reduce the severity of dextran sulfate sodium-induced colitis and enhance the abundance of the probiotics in the mice intestinal tract.

Minimally Invasive Full-endoscopic Posterior Cervical Foraminotomy and Discectomy: Introducing a Simple and Useful Localization Technique of the "V" Point.

OBJECTIVE: Conventional localization technique of V point for full-endoscopic posterior cervical foraminotomy and discectomy (FPCD) required repeated fluoroscopies, especially in patients with short and thick necks. To address this issue, the present study aimed to introduce a new localization technique of V point, and further evaluate its efficacy. METHODS: A K-wire was inserted and fixed at the pedicle eye under A/P fluoroscopy, then a working channel was established quickly along with it. Thirty-four patients who underwent minimally invasive FPCD assisted by the new technique were included in this study. The clinical and radiological data were collected and analyzed, including radiation dose, operative time, positioning time, visual analog scale (VAS) for neck and arm pain, neck disability index (NDI) scores, Cobb angle of operative level and range of motion of the cervical spine. RESULTS: All operations were performed successfully, and no iatrogenic nerve or vascular injury occurred. None of the patients needed to be transferred to open surgery or revision surgery. The mean radiation dose was found to be1.68 ± 0.36 mSv. The mean positioning time observed was 10.68 ± 5.42 min and the average operation time was 81.18 ± 10.87 min. The operation time significantly declined as the number of patients increased. A significant difference in operation time between the first (96.22 ± 10.36 min) and last quartile (75.00 ± 3.84 min) of cases was observed (t = 4.82, P < 0.001). The VAS scores for neck and arm pain, and NDI scores were significantly improved after surgery (PVAS-Neck <0.0001, PVAS-Arm <0.0001, PNDI <0.0001). Based on MacNab criteria, the excellent plus good rate was 91.17%. The Cobb angle of operative level and range of motion of the cervical spine were significantly improved postoperatively (t = 2.846, POA  = 0.015; t = 2.232, PROM-CA  = 0.026). CONCLUSION: The new image-assisted V point localization technique is simple and useful with little radiation exposure and short positioning time. FPCD assisted by the new technique could be a safe and effective alternative on properly selected patients.

C-type lectin domain-containing protein CLEC3A regulates proliferation, regeneration and maintenance of nucleus pulposus cells.

It is widely assumed that as connective tissue, the intervertebral disc (IVD) plays a crucial role in providing flexibility for the spinal column. The disc is comprised of three distinct tissues: the nucleus pulposus (NP), ligamentous annulus fibrous (AF) that surrounds the NP, and the hyaline cartilaginous endplates (CEP). Nucleus pulposus, composed of chondrocyte-like NP cells and its secreted gelatinous matrix, is critical for disc health and function. The NP matrix underwent dehydration accompanied by increasing fibrosis with age. The degeneration of matrix is almost impossible to repair, with the consequence of matrix stiffness and senescence of NP cells and intervertebral disc, suggesting the value of glycoproteins in extracellular matrix (ECM). Here, via database excavation and biological function screening, we investigated a C-type lectin protein, CLEC3A, which could support differentiation of chondrocytes as well as maintenance of NP cells and was essential to intervertebral disc homeostasis. Furthermore, mechanistic analysis revealed that CLEC3A could stimulate PI3K-AKT pathway to accelerate cell proliferation to further play part in NP cell regeneration.

Anti-inflammation and adhesion enhancement properties of the multifunctional LPxTG-motif surface protein derived from the Lactobacillus reuteri DSM 8533.

LPxTG-motif protein (LMP) is one kind of a precursor protein that contains a conserved LPxTG-motif at the C-terminus, which can be recognized by sortase A (SrtA) and covalently bind to the bacterial peptidoglycan. In this study, LMP derived from Lactobacillus reuteri (L. reuteri) was heterologous expressed and the tolerance and intestinal colonization ability of the LMP on L. reuteri were analyzed in simulated gastrointestinal fluid. Meanwhile, the anti-inflammatory activity of LMP was also evaluated in the LPS-stimulated RAW 264.7 cell model. The results indicated that LMP can promote the intestinal survival rate and adhesion characteristics of L. reuteri and enhanced the autoinducer-2 (AI-2) signaling molecule of the Lactobacillus strains in quorum sensing. Furthermore, LMP can inhibit the expressions of inflammatory cytokine TNF-α and IL-1ß via ERK-JNK related MAPK signaling cascades. These findings provide a better understanding of the multifunctional LPxTG-motif surface protein derived from L. reuteri in the gastrointestinal tract environment.

Adhesion properties of cell surface proteins in Lactobacillus strains in the GIT environment.

As a broadly defined member of lactic acid bacteria (LAB), the Lactobacillus strain is well characterized in food fermentation and specific strains can enhance the intestinal barrier function and be recognized as the probiotic strain. In recent years, many molecules of the cell surface are thought to be related to the adhesion property in the gastrointestinal mucosa. Mucus layer-related proteins, extracellular matrix proteins, and immunoglobulins also exhibit immunity regulation and protection of the intestinal epithelial barrier function. Meanwhile, the effects of bile and the low pH of the gastrointestinal tract (GIT) on Lactobacillus colonization are also needed to be considered. Furthermore, LAB can adhere and aggregate in the GIT to promote the maturity of biofilm and the extracellular matrix secreting through the signal molecules in the quorum sensing (QS) system. Therefore, it is of great interest to use the QS system to regulate the initial adhesion ability of Lactobacillus and further enhance the probiotic effect of the biofilm formation of beneficial bacteria. This review summarizes the adhesion properties of cell surface proteins derived from Lactobacillus strains in recent studies and provides valuable information on the QS effect on the adhesion property of Lactobacillus strains in the GIT environment.

Comparison of Accuracy and Clinical Outcomes of Robot-Assisted Versus Fluoroscopy-Guided Pedicle Screw Placement in Posterior Cervical Surgery.

STUDY DESIGN: This was a prospective controlled study. OBJECTIVE: To compare the accuracy and clinical outcomes of robot-assisted (RA) and fluoroscopy-guided (FG) pedicle screw placement in posterior cervical surgery. METHODS: This study included 58 patients. The primary outcome measures were the 1-time success rate and the accuracy of pedicle screw placement according to the Gertzbein-Robbins scales. The secondary outcome measures, including the operative time, intraoperative blood loss, hospital stay, cumulative radiation time, radiation dose, intraoperative advent events, and postoperative complications, were recorded and analyzed. The Japanese Orthopedics Association (JOA) scores and Neck Disability Index (NDI) were used to assess the neurological function of patients before and at 3 and 6 months after surgery. RESULTS: The rate of grade A was significantly higher in the RA group than in the FG group (90.6% and 71.1%; P < .001). The clinically acceptable accuracy was 97.2% in the RA group and 90.7% in the FG group (P = .009). Moreover, the 1-time success rate was significantly higher in the RA group than in the FG group. The RA group had less radiation time (P < .001) and less radiation dose (P = .002) but longer operative time (P = .001). There were no significant differences in terms of intraoperative blood loss, hospital stay, intraoperative adverse events, postoperative complications, JOA scores, and NDI scores at each follow-up time point between the 2 groups. CONCLUSIONS: The RA technique achieved higher accuracy and 1-time success rate of pedicle screw placement in posterior cervical surgery while achieving comparable clinical outcomes.

Selective thoracolumbar/lumbar fusion for Syringomyelia-associated scoliosis: a case-control study with Lenke 5C adolescent idiopathic scoliosis.

BACKGROUND: Selective thoracolumbar/lumbar fusion technique was introduced to treat adolescent idiopathic scoliosis (AIS) patients with major thoracolumbar/lumbar curves. Theoretically, this surgical strategy could also be applied to syringomyelia patients. No previous study has specifically addressed the effectiveness of selective thoracolumbar/lumbar fusion for patients with syringomyelia-associated scoliosis. The aim of the study was to investigate the effectiveness of selective thoracolumbar/lumbar fusion for the surgical treatment of patients with syringomyelia-associated scoliosis. METHODS: From February 2010 to September 2016, 14 syringomyelia-associated patients with major thoracolumbar/lumbar curves were retrospectively reviewed. Besides, 30 Lenke 5C AIS patients were enrolled as a control group. Posterior selective thoracolumbar/lumbar fusion was performed for both groups. Patients' demographic, operative, radiological, and quality of life data were reviewed with follow-up. Intragroup comparisons were performed for each parameter. RESULTS: The two groups were matched by age, gender, curve characteristics, duration of follow-up, and all preoperative radiographic parameters except for thoracic kyphosis. After surgery, the average correction rate of the major thoracolumbar/lumbar curve was 82.2 ± 7.8% in the syringomyelia group, which was not significantly different from that of AIS group (82.5 ± 10.6%, P = 0.47). A similar improvement of unfused thoracic curve was observed between the two groups (50.1 ± 16.5% vs. 48.5 ± 26.9%, P = 0.29). During the follow-up, the correction effect of scoliosis was well maintained, without aggravation of the original neural symptoms or fresh permanent neurological deficits. Of note, the number of fusion levels was significantly larger in syringomyelia group than that in AIS group (7.6 ± 1.4 vs. 6.5 ± 1.2, P < 0.01). The average follow up was 47.6 months (36-81 months). CONCLUSION: Similar to AIS cases, syringomyelia-associated scoliosis can be effectively and safely corrected by selective thoracolumbar/lumbar fusion with satisfactory surgical outcomes. However, the syringomyelia group, on average, required an additional fused segment for treatment as compared to the AIS group (7.6 versus 6.5 in the AIS group).

Different Surgical Strategy for Patients with Cervical Angina: A Potential Role of Luschka's Joint Osteophyte.

OBJECTIVE: Cervical angina is an underrecognized type of noncardiac chest pain and its mechanism of pain remains obscure. The objective of the current study was to investigate the clinical outcomes of different surgical strategies for patients with cervical angina and to analyze the potential pathogenesis of Luschka's joint osteophyte. METHODS: From February 2013 to March 2018, a prospective study on cervical angina was performed in our hospital. All patients who were diagnosed with both noncardiac chest pain and cervical pathology were identified. During admission, they consulted with a cardiologist and underwent strict cardiac workups to exclude true angina pectoris. The included 41 patients were randomly divided into two groups according to different surgical strategies of whether or not to remove Luschka's joint osteophyte during anterior cervical decompression surgery: the osteophyte resection (OR group) and the nonresection (NR group). RESULTS: The OR group consisted of 21 patients (8 men and 13 women) with a mean age of 54.7 years (range, 41-65 years). The NR group was composed of 20 patients (9 men and 11 women) with an average age of 56.3 years (range, 43-68 years). Before surgery, the mean duration of symptoms was 6.1 months (range, 4-20 months). The Luschka's joint osteophytes were located at C6 -C7 (19 cases, 46.3%), C5 -C6 (17 cases, 41.5%), and C4 -C5 (4 cases, 12.2%). Their average area was 34.85 mm2 and the average length were 5.09 mm. No statistically significant differences in demographic characteristics were detected between the two groups (P > 0.05). After operation, there were significant improvements in the Japanese Orthopedic Association score and the Neck Disability Index score in both groups (P < 0.05). However, the visual analogue scale score for chest pain in the OR group was statistically lower than that in the NR group (1.4 ± 1.0 vs 2.1 ± 1.6, P < 0.05). In the OR group, the results of cervical spine surgery were excellent in 18 patients (85.7%), and fair in 3 patients (14.3%). In the NR group, there were 10 patients (50.0%) with excellent results, 9 patients with fair results (45.0%), and 1 patient with poor results (5.0%). Notably, there were statistically significant differences between the two groups (χ2 = 6.265, P = 0.044). The average follow-up was 31 months (24-52 months). CONCLUSION: Anterior cervical decompression surgery with resection of Luschka's joint osteophyte can effectively reduce cervical angina symptom and improve the patient's quality of life. In addition to nerve root compression, Luschka's joint osteophyte may be another pathogenic factor in cervical angina.

Robot-assisted orthopedic surgery in the treatment of adult degenerative scoliosis: a preliminary clinical report.

STUDY DESIGN: A single-institution, retrospective cohort study. OBJECTIVE: To compare the accuracy and short-term clinical outcomes of pedicle screw placement between robot-assisted (RA) and freehand (FH) technique in the treatment of adult degenerative scoliosis (ADS). METHODS: From February 2018 to October 2019, 97 adult patients with degenerative scoliosis admitted to our department were retrospectively reviewed. Thirty-one patients received robot-assisted pedicle screw placement (RA group), and 66 patients underwent freehand pedicle screw placement (FH group). Patient demographics and short-term clinical outcomes were recorded and compared between two groups. Gertzbein-Robbins grading system was adopted to evaluate the accuracy of pedicle screw placement by means of postoperative CT scan. Short-term clinical outcomes consist of operative time, intraoperative blood loss, length of hospital stay (LOS), radiological parameters, Scoliosis Research Society-22 (SRS-22) scores before the operation, 6 months after operation, adverse events, and revisions. RESULTS: The accuracy of screw placement was higher than that of the FH group (clinically acceptable 98.7% vs. 92.2%; P< 0.001). Intraoperative blood loss of the RA group was less than those in the FH group (499 vs. 573 ml; P < 0.001). Operative time (283.1 vs. 291.9 min; P = 0.31) and length of stay (12.8 vs. 13.7 days; P = 0.36) were compared between RA and FH groups. In terms of radiological parameters, both of groups were improved postoperatively. The SRS-22 scores at 6 months after operation from both groups were better than those before operation. For surgery-related complication, one case had pressure sores in the RA group while two cases developed dural tears in the FH group. No revision was required in both groups. CONCLUSION: Combined with other surgical correction modalities, robot-assisted pedicle screw fixation is an effective and safe method of treating degenerative scoliosis. Due to its satisfactory surgical outcomes such as higher accuracy and less trauma, it provides a good alternative for clinical practice. LEVEL OF EVIDENCE: 3.

Comparison of anterior, posterior, and anterior combined with posterior surgical treatment of thoracic and lumbar spinal tuberculosis: a systematic review.

BACKGROUND: This study was performed to compare different surgical approaches in the treatment of spinal tuberculosis. METHODS: We conducted a literature search to identify and analyze papers published from January 1966 to April 2018 relevant to comparison of the anterior, posterior, and anterior combined with posterior approaches in the treatment of spinal tuberculosis of the thoracic and lumbar regions. RESULTS: Twenty-five studies involving 2295 patients were identified in this systematic review. The operative time was significantly longer in the anterior combined with posterior approach than in the other two approaches. Blood loss was significantly greater in the anterior combined with posterior approach (1125.0 ± 275.5 mL) than in the posterior approach (710.4 ± 192.4 mL). The difference in correction of the kyphosis angle among the three procedures was not significant. The overall surgical and transthoracic complications were significantly lower in the posterior approach. The clinical outcome of all patients improved, but there was no significant difference among the three procedures. CONCLUSIONS: Blood loss, overall surgical and transthoracic complications, and the operative time are different among the three approaches. Therefore, different factors must be carefully assessed in deciding among the three procedures.

Bone morphogenetic protein-2 promotes osteosarcoma growth by promoting epithelial-mesenchymal transition (EMT) through the Wnt/ß-catenin signaling pathway.

The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/ß-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while ß-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3ß were also significantly upregulated indicating that the Wnt/ß-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/ß-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638-1648, 2019.

p-Hydroxybenzyl Alcohol Prevents Memory Deficits by Increasing Neurotrophic Factors and Decreasing Inflammatory Factors in a Mice Model of Alzheimer's Disease.

p-hydroxybenzyl alcohol (HBA) is one of the major components of Gastrodia elata Blume (GEB) phenolic compound. HBA has been reported to have a protective effect on amyloid-ß (Aß) induced cell death. However, the systemic effects and the detail molecular mechanism of HBA in Alzheimer's disease (AD) animal models is not clear. In this study, we revealed the protective effects and the potential mechanisms of HBA on the impairments of cognitive function induced by soluble Aß oligomers. Our results showed that HBA prevented neuronal cells death in a dose-dependent manner. The working memory and the spatial memory were significantly lower in AD model mice. HBA treatment prevented the memory deficits of the AD mice. HBA treatment significantly prevented the decreased spine density and decreased expression levels of synaptic proteins induced by Aß42. In addition, both mRNA levels and protein levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the Aß42-treated mice were decreased, the decreases were prevented by HBA treatment. The expression levels of TNF-α and IL-1ß were increased by Aß42 treatment and the increase can be prevented by the HBA treatment. Moreover, HBA prevents the decreases in the level of nuclear erythroid 2 p45-related factor 2 (Nrf2) induced by Aß42 in hippocampal. Thus, we predict that HBA might prevent Aß42 oligomer-induced synapse and cognitive impairments through multiple targets including increasing Nrf2, increasing neurotrophic factors and decreasing inflammatory factors. Our study provided novel insights into the cellular mechanisms for the protective effects of HBA on AD.

Comparison of Effects of PELD and Fenestration in the Treatment of Geriatric Lumbar Lateral Recess Stenosis.

PURPOSE: Although degenerative lumbar spinal stenosis (LSS) is increasingly being diagnosed in older people, there is much uncertainty about the appropriate operative treatment options. The objective of this study was to compare the outcome of percutaneous endoscopic lumbar decompression (PELD) versus fenestration for lumbar lateral recess stenosis (LRS) in geriatric patients over 75 years old. MATERIALS AND METHODS: This prospective controlled study was performed on 46 consecutive over aged patients with lateral recess stenosis who underwent either PELD or fenestration. Clinical data were recorded before, 1 week, 3 months and 1.5 years after surgery using visual analog scale (VAS), Japanese Orthopaedic Association Score (JOA), The Short-Form-36 (SF-36), and the modified Macnab evaluation criteria. RESULTS: The patients' mean age was 82.7 years (aged 75-93 years) in PELD group and 79.1 years (aged 75-88 years) in fenestration group. No statistical difference was found between PELD group and fenestration group with regards to VAS-back pain, VAS-leg pain, JOA and at 3 months and 1.5-year follow-up. However, the PELD group had a lower mean VAS for back pain at 1 week postoperatively (P<0.05). The quality of life in PELD group achieved the same remarkable improvement as fenestration group (P>0.05). Operative time (min) was similar between two groups (p>0.05), while the PELD techniques brought advantages in blood loss (mL) (48.3 vs 128.2, p<0.05), early ambulation (h) (5.5 vs 25.2, p<0.05), and anesthesia-related complications. CONCLUSION: Both PELD and fenestration showed favorable clinical outcomes for the treatment of lumbar lateral recess stenosis. In addition, PELD had advantages such as reduced traumatization and less anesthesia-related complications. In terms of quality of life and complications after operation, PELD under local anesthesia could be an efficient supplement to conventional decompression surgery in geriatric patients with lumbar lateral recess stenosis.

Paclitaxel Induce Apoptosis of Giant Cells Tumor of Bone via TP53INP1 Signaling.

OBJECTIVE: To evaluate the antitumor capability and to investigate the underlying molecular mechanism of paclitaxel. METHODS: First, cck-8 and apoptosis assays were used to determine survival and apoptotic effects of HS 737.T cells under treatment of paclitaxel. Next, RNA-seq and bioinformatics were used to determine the differentially expressed genes and to analyze the pathway involved. Quantitative real-time polymerase chain reaction was used to verify the accuracy of some differentially expressed genes (DEG). ClueGO was used to decode and visualize functionally grouped GO terms of differentially expressed genes, and to map the DEG protein-protein interactions (PPI) network. Western blotting was used to check the expression of target genes, the cleavage of Caspase-3 and PARP1, and the phosphorylation level of p53. Finally, transcriptomics, bioinformatics, and RNAi were used to estimate the antitumor capability and to identify the underlying mechanisms of paclitaxel in GCTB. RESULTS: Our data revealed that paclitaxel had significant time-dependent effects on the viability and induced apoptosis of HS 737.T cells. RNA-seq and bioinformatics analysis showed that apoptosis, death receptor signaling pathway, TNF signaling pathway, and TP53 regulated transcription of cell death genes pathway were closely associated with paclitaxel in the treatment of GCTB. Western bolt results revealed that paclitaxel induced cleavage of Caspase-3 and PARP1, and increased the phosphorylation level of p53 in HS 737.T cells. RNAi results showed that the expression level of TP53INP1 was significantly decreased in HS737.T cells (the decrease was more than 70%). In addition, we found that the inhibitory ratios of paclitaxel on HS737.T cells deficient in TP53INP1 were less than in HS737.T cells with empty vector (19.88 and 40.60%, respectively). Hence, our data revealed that TP53INP1 regulated paclitaxel-driven apoptosis in HS737.T cells. CONCLUSION: Paclitaxel can significantly repress cell proliferation and induce apoptosis of HS 737.T cells through activating Caspase-3, PARP1, p53, and TP53INP1. Paclitaxel may be an effective drug in the management of GCTB.

LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.

OBJECTIVE: Accumulating data show that dysregulation of long noncoding RNAs (lncRNAs) acts a critical role in a variety of malignancies. Among these lncRNAs, small nucleolar RNA host genes (SNHGs) are associated with tumour growth and progression. But, the molecular mechanisms by which SNHG4 contributes to osteosarcoma remain undocumented. METHODS: The association between lncRNA SNHG4 expression and clinicopathologic characteristics and prognosis in patients with osteosarcoma was analysed by TCGA RNA-sequencing data. Cell viability and colony formation abilities were respectively assessed by MTT and colony formation assays. LncRNA SNHG4-specific binding with miR-224-3p was verified by bioinformatic analysis, luciferase gene report, and RNA immunoprecipitation assays. Regulation relationship between SNHG4 and miR-224-3p expression was further evaluated by the rescue experiments. RESULTS: The expression level of lncRNA SNHG4 was significantly elevated in osteosarcoma samples and cell lines as compared with the adjacent normal tissues, and SNHG4 high expression was associated with tumour size (TS) and poor prognosis in patients with osteosarcoma. Knockdown of SNHG4 suppressed cell viability and invasive potential, whereas ectopic SNHG4 expression displayed the opposite effects. Moreover, we found that lncRNA SNHG4 acted as a sponge of miR-224-3p, and miR-224-3p mimic reversed SNHG4 induced tumour-promoting effects in osteosarcoma cells. The expression of miR-224-3p depicted a negative correlation with SNHG4 in osteosarcoma samples and miR-224-3p low expression was associated with TS and poor survival in patients with osteosarcoma. CONCLUSION: Our findings demonstrated that LncRNA SNHG4 promoted tumour growth by sponging miR-224-3p and represented a poor prognostic factor in patients with osteosarcoma.

miR-149-5p inhibits cell growth by regulating TWEAK/Fn14/PI3K/AKT pathway and predicts favorable survival in human osteosarcoma.

MicroRNAs (miRNAs) as small non-coding RNAs act as either tumor suppressors or oncogenes in human cancers, of which miR-149-5p (miR-149) is involved in tumor growth and metastasis, but its role and molecular mechanisms underlying osteosarcoma growth are poorly understood. The correlation of miR-149 expression with clinicopathological characteristics and prognosis in patients with sarcoma was analyzed by The Cancer Genome Atlas (TCGA) RNA-sequencing data. Osteosarcoma cell growth affected by miR-149 was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. As a result, we found that the expression level of miR-149 was markedly downregulated in human sarcoma samples and were negatively associated with tumor size, acting as an independent prognostic factor for overall survival of the sarcoma patients. Restoration of miR-149 expression suppressed osteosarcoma cell growth, while its knockdown reversed these effects. Furthermore, we identified TNFRSF12A (TNF receptor superfamily member 12A), also called fibroblast growth factor-inducible 14 (Fn14) as a direct target of miR-149, and TNFRSF12A and its ligand TNFSF12 (TNF superfamily member 12), also called tumor necrosis factor-related weak inducer of apoptosis (TWEAK), were both negatively correlated with miR-149 expression in sarcoma samples. Knockdown of TNFRSF12A suppressed cell growth, but its overexpression weakened the antiproliferative effects of miR-149 via the PI3K/AKT (AKT serine/threonine kinase) signaling pathway. Altogether, our findings show that miR-149 functions as a tumor suppressor in osteosarcoma via inhibition of the TWEAK-Fn14 axis and represents a potential therapeutic target in patients with osteosarcoma.