Peripheral nerve transfers for dysfunctions in central nervous system injuries: a systematic review.

BACKGROUND: The review highlights recent advancements and innovative uses of nerve transfer surgery in treating dysfunctions caused by central nervous system (CNS) injuries, with a particular focus on spinal cord injury (SCI), stroke, traumatic brain injury, and cerebral palsy. METHODS: A comprehensive literature search was conducted regarding nerve transfer for restoring sensorimotor functions and bladder control following injuries of spinal cord and brain, across PubMed and Web of Science from January 1920 to May 2023. Two independent reviewers undertook article selection, data extraction, and risk of bias assessment with several appraisal tools, including the Cochrane Risk of Bias Tool, the JBI Critical Appraisal Checklist, and SYRCLE's ROB tool. The study protocol has been registered and reported following PRISMA and AMSTAR guidelines. RESULTS: Nine hundred six articles were retrieved, of which 35 studies were included (20 on SCI and 15 on brain injury), with 371 participants included in the surgery group and 192 in the control group. These articles were mostly low-risk, with methodological concerns in study types, highlighting the complexity and diversity. For SCI, the strength of target muscle increased by 3.13 of Medical Research Council grade, and the residual urine volume reduced by more than 100 ml in 15 of 20 patients. For unilateral brain injury, the Fugl-Myer motor assessment (FMA) improved 15.14-26 score in upper extremity compared to 2.35-26 in the control group. The overall reduction in Modified Ashworth score was 0.76-2 compared to 0-1 in the control group. Range of motion (ROM) increased 18.4-80° in elbow, 20.4-110° in wrist and 18.8-130° in forearm, while ROM changed -4.03°-20° in elbow, -2.08°-10° in wrist, -2.26°-20° in forearm in the control group. The improvement of FMA in lower extremity was 9 score compared to the presurgery. CONCLUSION: Nerve transfer generally improves sensorimotor functions in paralyzed limbs and bladder control following CNS injury. The technique effectively creates a 'bypass' for signals and facilitates functional recovery by leveraging neural plasticity. It suggested a future of surgery, neurorehabilitation and robotic-assistants converge to improve outcomes for CNS.

MSC-Based Cell Therapy in Neurological Diseases: A Concise Review of the Literature in Pre-Clinical and Clinical Research.

Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to self-renew and multi-directional differentiation potential. Exogenously administered MSCs can migrate to damaged tissue sites and participate in the repair of damaged tissues. A large number of pre-clinical studies and clinical trials have demonstrated that MSCs have the potential to treat the abnormalities of congenital nervous system and neurodegenerative diseases. Therefore, MSCs hold great promise in the treatment of neurological diseases. Here, we summarize and highlight current progress in the understanding of the underlying mechanisms and strategies of MSC application in neurological diseases.

GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis.

Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the AKT/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the AKT/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.

A bibliometric analysis of brachial plexus injury from 1980 to 2022.

Background: Brachial plexus injury is a common severe peripheral nerve injury with high disability. At present, the bibliometric analysis of brachial plexus injury is basically unknown. Methods: This article analyzes the data retrieved to the web of science and uses the R language (version 4.2), Citespace (version 6.1.R3 Advanced), Vosviewer (Lei deng university) to make a scientific map. Specifically, we analyze the main publication countries, institutions, journals where the article is published, and the cooperative relationship between different institutions, the relationship between authors, main research directions in this field, and current research hotspots. Results: From 1980 to 2022, the total number of publications is 1542. In terms of countries where articles were published, 551 records were published in the United States, accounting for 35% of the total. With 74 articles, Fudan University ranks first in the world in terms of the number of articles issued by the institution, followed by 72 articles from Mayo Clinic. The magazine with the largest number of articles is JOURNAL OF HAND SURGERY-AMERICAN VOLUME, which has published 87 articles in total. GU YD (Gu Yu-Dong) team (Fudan University) and spinner RJ (Robert J Spinner) team (Mayo clinic) are in a leading position in this field. Nerve transfer and nerve reconstruction have been a hot topic of brachial plexus injury. "Spinal nerve root repair and reimplantation of avulsed ventral roots into the spinal cord after brachial plexus injury" has the strongest citation bursts. Conclusion: Research on brachial plexus injury shows a trend of increasing heat. At present, there is a lack of communication and cooperation between scholars from different countries. Nerve transfer and nerve reconstruction are the current and future research directions in the treatment of brachial plexus injury.

ADSC-Exos enhance functional recovery after spinal cord injury by inhibiting ferroptosis and promoting the survival and function of endothelial cells through the NRF2/SLC7A11/GPX4 pathway.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes major motor, sensory and autonomic dysfunctions. Currently, there is a lack of effective treatment. In this study, we aimed to investigate the potential mechanisms of Exosomes from adipose-derived stem cells (ADSC-Exos) in reducing ferroptosis and promoting angiogenesis after spinal cord injury. METHODS: We isolated ADSC-Exos, the characteristics of which were confirmed. In vitro, we tested the potential of ADSC-Exos to promote the survival and function of human brain microvascular endothelial cells (HBMECs) and analyzed the ferroptosis of HBMECs. In vivo, we established rat models of SCI and locally injected ADSC-Exos to verify their efficacy. RESULTS: ADSC-Exos can reduce reactive oxygen species (ROS) accumulation and cell damage induced by an excessive inflammatory response in HBMECs. ADSC-Exos inhibit ferroptosis induced by excessive inflammation and upregulate the expression of glutathione peroxidase 4(GPX4) in HBMECs. It can also effectively promote proliferation, migration, and vessel-like structure formation. In vitro, ADSC-Exos improved behavioral function after SCI and increased the number and density of blood vessels around the damaged spinal cord. Moreover, we found that ADSC-Exos could increase nuclear factor erythroid-2-related factor 2(NRF2) expression and nuclear translocation, thereby affecting the expression of solute carrier family 7 member 11(SLC7A11) and GPX4, and the NRF2 inhibitor ML385 could reverse the above changes. CONCLUSION: Our results suggest that ADSC-Exos may inhibit ferroptosis and promote the recovery of vascular and neural functions after SCI through the NRF2/SLC7A11/GPX4 pathway. This may be a potential therapeutic mechanism for spinal cord injury.

Transforaminal endoscopic lumbar discectomy using a 45° puncture angle and foraminotomy versus traditional THESYS for L5/S1 lumbar disc herniation: a prospective randomized controlled trial.

PURPOSE: Prospective comparison of the efficacy and safety of transforaminal endoscopic lumbar discectomy (TELD) with a 45° puncture angle versus traditional Thomas Hoogland endoscopy spine systems (THESYS) for the surgical treatment of L5/S1 lumbar disc herniation (LDH). METHODS: Consecutive patients with L5/S1 LDH who underwent TELD were randomized (1:1) assigned to the 45° TELD group and the THESYS group. Clinical outcomes were assessed at pre-operation, 1-day and 3/6-months post-operation till final follow-up. Surgical-related parameters, visual analogue scale (VAS) score, oswestry disability index (ODI), and modified MacNab criteria, and surgical complications were recorded and analysed. RESULTS: All patients were followed up for at least 24 months. Compared to the THESYS group, the 45° TELD group had a shorter operative time (P < 0.001) and intraoperative radiation time (P < 0.001) and a smaller VAS score for back pain (P < 0.001) and leg pain intraoperatively (P < 0.001). The VAS and ODI in the 45° TELD group were significantly better than those in the THESYS group within 3 months postoperatively. However, from 3 months on, both groups showed comparable VAS and ODI. There was no significant difference between the two groups of modified MacNab criteria. There were two cases of residual disc and two cases of recurrence that required reoperation in the THESYS group. CONCLUSION: For L5/S1 LDH, the 45° TELD technique was superior to traditional THESYS in terms of surgery-related parameters and faster improvement of VAS and ODI, with a lower complication rate.

Pan-cancer analysis of 60S Ribosomal Protein L7-Like 1 (RPL7L1) and validation in liver hepatocellular carcinoma.

BACKGROUND AND AIMS: There is an association between cancer and increased ribosome biogenesis. At present, the RPL7L1 (60S Ribosomal Protein L7-Like 1) were less reported by literature search. Study reports that RPL7L1 is associated with mouse embryonic and skeletal muscle. The study of RPL7L1 on tumors has not been reported. METHODS: Our team downloaded the pan-cancer dataset that is uniformly normalized from the UCSC database (N=19131). Our study examined the relationship between RPL7L1 expression level and clinical prognosis with methylation, anti-tumour immunity, functional states, MSI, TMB, DNSss, LOH and chemotherapeutic responses in 43 cancer types and subtypes. RESULTS AND CONCLUSIONS: RPL7L1 was overexpressed in nine tumor types. Gene mutation, tumor microenvironment and methylation modification of RPL7L1 plays a key role in patient prognosis. And the high expression of RPL7L1 was associated with TMB, MSI, LOH especially LIHC and HNSC. We experimentally verified that genes can promote the proliferation and migration of tumor cells. Our study suggested that RPL7L1 biomarker can be used for treating cancer, detecting it, and predicting its prognosis.

Tuina therapy promotes behavioral improvement and brain plasticity in rats with peripheral nerve injury and repair.

INTRODUCTION: Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short-term and long-term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. METHODS: A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block-design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a "boxcar" paradigm. RESULTS: When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain-regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. CONCLUSION: Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain-related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity.

Efficacy of image-enhanced endoscopy for colorectal adenoma detection: A multicenter, randomized trial.

BACKGROUND: Improved adenoma detection at colonoscopy has decreased the risk of developing colorectal cancer. However, whether image-enhanced endoscopy (IEE) further improves the adenoma detection rate (ADR) is controversial. AIM: To compare IEE with white-light imaging (WLI) endoscopy for the detection and identification of colorectal adenoma. METHODS: This was a multicenter, randomized, controlled trial. Participants were enrolled between September 2019 to April 2021 from 4 hospital in China. Patients were randomly assigned to an IEE group with WLI on entry and IEE on withdrawal (n = 2113) or a WLI group with WLI on both entry and withdrawal (n = 2098). The primary outcome was the ADR. The secondary endpoints were the polyp detection rate (PDR), adenomas per colonoscopy, adenomas per positive colonoscopy, and factors related to adenoma detection. RESULTS: A total of 4211 patients (966 adenomas) were included in the analysis (mean age, 56.7 years, 47.1% male). There were 2113 patients (508 adenomas) in the IEE group and 2098 patients (458 adenomas) in the WLI group. The ADR in two group were not significantly different [24.0% vs 21.8%, 1.10, 95% confidence interval (CI): 0.99-1.23, P = 0.09]. The PDR was higher with IEE group (41.7%) than with WLI group (36.1%, 1.16, 95%CI: 1.07-1.25, P = 0.01). Differences in mean withdrawal time (7.90 ± 3.42 min vs 7.85 ± 3.47 min, P = 0.30) and adenomas per colonoscopy (0.33 ± 0.68 vs 0.28 ± 0.62, P = 0.06) were not significant. Subgroup analysis found that with narrow-band imaging (NBI), between-group differences in the ADR, were not significant (23.7% vs 21.8%, 1.09, 95%CI: 0.97-1.22, P = 0.15), but were greater with linked color imaging (30.9% vs 21.8%, 1.42, 95%CI: 1.04-1.93, P = 0.04). the second-generation NBI (2G-NBI) had an advantage of ADR than both WLI and the first-generation NBI (27.0% vs 21.8%, P = 0.01; 27.0% vs 21.2.0%, P = 0.01). CONCLUSION: This prospective study confirmed that, among Chinese, IEE didn't increase the ADR compared with WLI, but 2G-NBI increase the ADR.

Impacts of pre-existing diabetes mellitus on colorectal cancer in a mice model.

BACKGROUND: Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre-existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression. METHODS: In this study, we investigated the effects of DM on CRC progression in a streptozotocin-induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA-seq. RESULTS: Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM-CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4+ T cells, CD8+ T cells and mucosal-associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM. CONCLUSION: For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre-existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.

Endoscopic mucosal resection of gastrointestinal polyps with a novel low-temperature plasma radio frequency generator: a non-inferiority multi-center randomized control study.

BACKGROUND: To evaluate the efficacy and safety of novel plasma radio frequency generator and its single-use polypectomy snares for endoscopic mucosal resection (EMR) of gastrointestinal (GI) polyps. METHODS: A total of 217 patients with 413 GI polyps were recruited from four centers in China. Patients were assigned to experimental or control groups using a central randomization method. The experimental group used the novel plasma radio frequency generator and its matched single-use polypectomy snares (Neowing, Shanghai), while the control group used the high-frequency electrosurgical unit (Erbe, Germany) and disposable electrosurgical snares (Olympus, Japan). The primary endpoint was the en bloc resection rate, and the non-inferiority margin was set at 10%. Secondary endpoint included operation time, coagulation success rate, intraoperative and postoperative bleeding rate, and perforation rate. RESULTS: The en bloc resection rate was 97.20% (104/107) in the experimental group and 95.45% (105/110) in the control group (P = 0.496). The operation time was 29.14 ± 20.21 min in the experimental group and 30.26 ± 18.74 min in the control group (P = 0.671). The average removal time of a single polyp in the experimental group was 7.52 ± 4.45 min, which was slightly shorter than that in the control group 8.90 ± 6.67 min, with no statistical difference (P = 0.076). The intraoperative bleeding rates of the experimental group and control group were 8.41% (9/107) and 10.00% (11/110), respectively (P = 0.686). No intraoperative perforation occurred in either group. The postoperative bleeding rates of the experimental group and the control group were 1.87% (2/107) and 4.55% (5/110), respectively (P = 0.465). No postoperative perforation occurred in the experimental group (0/107), while one case of delayed perforation occurred in the control group (1/110, 0.91%). There was no statistical difference between the two groups. CONCLUSIONS: Endoscopic mucosal resection of GI polyps with the novel plasma radio frequency generator is safe and effective, and non-inferior to the conventional high-frequency electrosurgical system.

Comparison of Single-level Cervical Radiculopathy Outcomes Between Posterior Endoscopic Cervical Decompression and Anterior Cervical Discectomy and Fusion: Mid-term Results.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the mid-term results and technical possibilities of posterior endoscopic cervical decompression (PECD) in the treatment of cervical radiculopathy. SUMMARY OF BACKGROUND DATA: PECD has been used in the treatment of cervical radiculopathy for the past decades; there is a paucity of studies directly comparing its outcomes with anterior cervical discectomy and fusion (ACDF) for patients with single-level cervical radiculopathy. PATIENTS AND METHODS: From January 2016 to December 2018, clinical and radiologic data of 42 patients were collected. Patients were followed for a mean of 40.6 months (range: 30-54 mo) after surgery. Changes in cervical lordosis and degeneration of adjacent segments were analyzed. Dysphagia was assessed using the Bazaz score, and clinical outcomes were analyzed using the Neck Disability Index and visual analog scoring system. RESULTS: There were no significant differences in neurological outcomes between the two groups. Significant between-group differences in postoperative dysphagia were observed ( P < 0.05). There were significant differences in postoperative segmental Cobb angles and disc height between the two groups ( P < 0.05). Degenerative changes in the adjacent segments occurred in 5 patients in the ACDF group and 1 patient in the PECD group ( P < 0.05); no revision surgery was needed. CONCLUSIONS: Clinical outcomes of PECD for patients with unilateral radiculopathy were satisfactory. On the premise of a strict selection of indications, we consider this technique to be a safe supplement and alternative to ACDF for patients with unilateral cervical radiculopathy. Longer follow-up periods are required to confirm these observations.

Osteochondral Autograft From the Hamate for Treating Partial Defect of the Proximal Interphalangeal Joint.

PURPOSE: The management of a proximal interphalangeal (PIP) joint fracture dislocation becomes more challenging when the joint surface is damaged because of severe comminution or inadequate treatment in the acute phase. The purpose of this study was to evaluate the clinical outcomes of an osteochondral autograft for the reconstruction of the joint surface in patients with a partial PIP joint defect. METHODS: Twelve patients underwent osteochondral autograft surgery from May 2007 to July 2018. The average age at the time of surgery was 38 years (range, 21-67 years), and there were 10 men and 2 women. Plain radiographs and computed tomography scans showed a partial middle phalangeal base defect in all the cases. The surgeries were performed 2 weeks to 20 months after the fracture or a previous surgery. Partial hamate grafts were harvested to reconstruct volar lip (n = 7), middle portion (n = 2), and dorsal lip (n = 3) defects of the middle phalangeal base. Bone healing, postoperative range of motion, instability, and pain were evaluated. The average follow-up duration was 27.8 months (range, 12-53 months). RESULTS: Radiographic graft union was observed in all the patients 6-8 weeks after the surgery. The deformity was corrected in 11 patients. The active range of motion of the involved PIP joint was improved from 28.3° (range, 0°-60°) to 75.0° (range, 25°-95°). Complications were observed during follow-up, including degenerative arthritis (n = 2), instability (n = 3), and stiffness (n = 5). CONCLUSIONS: Various types of partial joint defects of the middle phalangeal base following a PIP fracture dislocation can be reconstructed using an osteochondral autograft from the hamate. The functional recovery is generally acceptable, with a well-restored joint architecture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Clinical Application of Ultrasound-guided Electrode Placement and Detection of Nerve Action Potential.

BACKGROUND: We explore a minimally invasive method (combined ultrasound detection, electrode placement and electrophysiologic nerve examination) to evaluate the early-stage quality of a nerve suture site. METHODS: Ten patients with median and/or ulnar nerve injuries who had undergone nerve suture were recruited. Postoperative ultrasound examination found that the nerve injury was sutured. Then, a stimulating electrode and recording electrode were located beside the nerve proximal and distal to the suture site guided by ultrasound. Measurement of nerve action potentials (NAP) were performed with these electrodes, followed by surgical exploration. The pre- and intraoperative electrophysiologic findings were compared, together with amplitude, latency, and wave shape of NAP. RESULTS: Of the 10 patients, 3 patients were diagnosed with median nerve injury, 2 with ulnar nerve injury, and 5 with the median nerve and ulnar nerve injury. NAP could not be detected pre- and intraoperatively in three median nerves from three patients and in two ulnar nerves from two patients. NAP was detected in 10 nerves from the remaining 5 patients. The pre- and intraoperative NAP results showed consistent results concerning the status of the nerve suture. Wilcoxon's signed-rank test indicated no significant difference in the amplitude and latency detected via sonographically placed electrodes and during surgical exploration. The number of negative-phase waves were equally distributed. CONCLUSION: Ultrasound-guided electrode placement and NAP detection can substitute surgery and serve as a minimally invasive approach to evaluate the regeneration of a sutured nerve.

Effect of music-based movement therapy on the freezing of gait in patients with Parkinson's disease: A randomized controlled trial.

Background: Progression of freezing of gait (FOG), a common pathological gait in Parkinson's disease (PD), has been shown to be an important risk factor for falls, loss of independent living ability, and reduced quality of life. However, previous evidence indicated poor efficacy of medicine and surgery in treating FOG in patients with PD. Music-based movement therapy (MMT), which entails listening to music while exercising, has been proposed as a treatment to improve patients' motor function, emotions, and physiological activity. In recent years, MMT has been widely used to treat movement disorders in neurological diseases with promising results. Results from our earlier pilot study revealed that MMT could relieve FOG and improve the quality of life for patients with PD. Objective: To explore the effect of MMT on FOG in patients with PD. Materials and methods: This was a prospective, evaluator-blinded, randomized controlled study. A total of 81 participants were randomly divided into music-based movement therapy group (MMT, n = 27), exercise therapy group (ET, n = 27), and control group (n = 27). Participants in the MMT group were treated with MMT five times (1 h at a time) every week for 4 weeks. Subjects in the ET group were intervened in the same way as the MMT group, but without music. Routine rehabilitation treatment was performed on participants in all groups. The primary outcome was the change of FOG in patients with PD. Secondary evaluation indicators included FOG-Questionnaire (FOG-Q) and the comprehensive motor function. Results: After 4 weeks of intervention, the double support time, the cadence, the max flexion of knee in stance, the max hip extension, the flexion moment of knee in stance, the comprehensive motor function (UPDRS Part III gait-related items total score, arising from chair, freezing of gait, postural stability, posture, MDS-UPDRS Part II gait-related items total score, getting out of bed/a car/deep chair, walking and balance, freezing), and the FOG-Q in the MMT group were lower than that in the control group and ET group (p < 0.05). The gait velocity, the max ankle dorsiflexion in stance, ankle range of motion (ROM) during push-off, ankle ROM over gait cycle, the knee ROM over gait cycle, and the max extensor moment in stance (ankle, knee) in the MMT group were higher than that in the control group and ET group (p < 0.05). However, no significant difference was reported between the control group and ET group (p > 0.05). The stride length and hip ROM over gait cycle in the MMT group were higher than that in the control group (p < 0.05), and the max knee extension in stance in the MMT group was lower than that in the control group (p < 0.05). Nevertheless, there was no significant difference between the ET group and MMT group (p > 0.05) or control group (p > 0.05). Conclusion: MMT improved gait disorders in PD patients with FOG, thereby improving their comprehensive motor function.

Transforaminal endoscopic lumbar discectomy with targeted puncture and foraminotomy for very highly migrated disc herniation: A technique note with case series.

Background: Transforaminal endoscopic lumbar discectomy (TELD) has been widely used for lumbar disc herniation. However, in some challenging cases such as very highly migrated disc herniation (VHMDH), traditional TELD is difficult to access the pathology. Methods: From January 2016 to December 2019, 63 patients with single-level VHMDH underwent TELD using targeted puncture and foraminotomy techniques were included. All patients were followed up for 26.5 months on average (range, 24-48 months). Operative time, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and surgical complications were evaluated. Results: The operative time was 40-120 min (56.8 on average). The length of hospitalization was 2.5 days (range, 2-4 d). VAS score decreased significantly from 5.5 ± 1.3 preoperatively to 1.9 ± 1.30 (p < 0.001) 1 day postoperatively, and to 0.9 ± 0.8 (p < 0.001) at the final follow-up. ODI score improved significantly from 23.5 ± 3.2 preoperatively to 13.4 ± 3.0 (p < 0.001) 1 day postoperatively; and 3.1 ± 1.2 (p < 0.001) at the final follow-up. According to the modified MacNab criteria, 40 patients (63.5%) showed excellent results, 20 patients (31.7%) were rated as good, 2 patients (3.2%) were rated as fine, and 1 patient (1.6%) was rated as bad at the final follow-up. No residual fragments, nerve root or cauda equina injury was shown in this series. One recurrent case was resolved by open surgery. Conclusions: With modified targeted puncture and foraminotomy techniques, VHMDH can be accessed safely and effectively, and satisfactory clinical outcomes can be obtained for these patients.

Transforaminal Versus Interlaminar Approach of Full-Endoscopic Lumbar Discectomy Under Local Anesthesia for L5/S1 Disc Herniation: A Randomized Controlled Trial.

BACKGROUND: Local anesthesia is feasible for both transforaminal and interlaminar approaches in percutaneous endoscopic lumbar discectomy (PELD). However, the optimal approach for PELD has not yet been established at the L5/S1 segment under local anesthesia with 1% lidocaine. OBJECTIVES: In this study, we compared the transforaminal approach with the interlaminar approach of PELD under local anesthesia for L5/S1 disc herniation (DH). STUDY DESIGN: This was a prospective randomized clinical trial. METHODS: From January 2019 to March 2020, 91 consecutive patients with L5/S1 DH who planned to undergo PELD in our unit were randomized to the transforaminal endoscopic lumbar discectomy (TELD, n = 46) or interlaminar endoscopic lumbar discectomy (IELD, n = 45). Both procedures were performed under local anesthesia with 1% lidocaine. The clinical outcomes were assessed as the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, and modified MacNab criteria. Patient satisfaction surveys and surgical complications were also recorded and analyzed. RESULTS: Compared to the IELD group, the TELD group had a shorter operative time and postoperative bed rest time (P < 0.001) but a longer radiation time (P < 0.001) and lower VAS scores for intraoperative back pain (P < 0.001) and leg pain (P < 0.001). At the postoperative follow-up, there were no significant differences between the 2 groups in the VAS scores, ODI scores, or modified MacNab criteria. The surveys showed a significantly higher satisfaction rate in the TELD group than in the IELD group (P = 0.014). Six patients in the IELD group (13.3%) needed extra intravenous injections of sufentanil because of intense pain during the procedure. In the IELD group, there were 2 cases of neuropathic pain after surgery. LIMITATIONS: Due to the study was included in a single spine center with a relatively small population and its relatively short-term follow-up, the study is not generalizable. CONCLUSIONS: Both TELD and IELD can provide good clinical outcomes for L5/S1 DH under local anesthesia with 1% lidocaine. TELD was superior to IELD in terms of surgical-related experience and complications.

EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1.

OBJECTIVE: EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. METHODS: A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. RESULTS: EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. CONCLUSION: Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways.

BACKGROUND: The repair of cranio-maxillofacial bone defects remains a formidable clinical challenge. The Ets variant 2 (ETV2) transcription factor, which belongs to the E26 transformation-specific (ETS) family, has been reported to play a key role in neovascularization. However, the role of ETV2 in the osteogenesis of human dental pulp stem cells (hDPSCs) remains unexplored. METHODS: Transgenic overexpression of ETV2 was achieved using a lentiviral vector, based on a Dox-inducible system. The effects of Dox-induced overexpression of ETV2 on the osteogenesis of hDPSCs were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunofluorescence staining, alkaline phosphatase (ALP) staining, and Alizarin Red S (ARS) staining. Additionally, RNA-sequencing (RNA-Seq) analysis was performed to analyze the underlying mechanisms of ETV2-induced osteogenesis. Additionally, the role of ETV2 overexpression in bone formation in vivo was validated by animal studies with a rat calvarial defect model and a nude mice model. RESULTS: Our results demonstrated that ETV2 overexpression significantly upregulated the mRNA and protein expression levels of osteogenic markers, markedly enhanced ALP activity, and promoted matrix mineralization of hDPSCs. Moreover, the results of RNA-Seq analysis and western blot showed that the ERK/MAPK and PI3K-Akt signaling pathways were activated upon transgenic overexpression of ETV2. The enhanced osteogenic differentiation of hDPSCs due to ETV2 overexpression was partially reversed by treatment with inhibitors of ERK/MAPK or PI3K-AKT signaling. Furthermore, the results of in vivo studies demonstrated that ETV2 overexpression improved bone healing in a rat calvarial defect model and increased ectopic bone formation in nude mice. CONCLUSIONS: Collectively, our results indicated that ETV2 overexpression exerted positive effects on the osteogenesis of hDPSCs, at least partially via the ERK/MAPK and PI3K/AKT signaling pathways.

ROS-activated CXCR2+ neutrophils recruited by CXCL1 delay denervated skeletal muscle atrophy and undergo P53-mediated apoptosis.

Neutrophils are the earliest master inflammatory regulator cells recruited to target tissues after direct infection or injury. Although inflammatory factors are present in muscle that has been indirectly disturbed by peripheral nerve injury, whether neutrophils are present and play a role in the associated inflammatory process remains unclear. Here, intravital imaging analysis using spinning-disk confocal intravital microscopy was employed to dynamically identify neutrophils in denervated muscle. Slice digital scanning and 3D-view reconstruction analyses demonstrated that neutrophils escape from vessels and migrate into denervated muscle tissue. Analyses using reactive oxygen species (ROS) inhibitors and flow cytometry demonstrated that enhanced ROS activate neutrophils after denervation. Transcriptome analysis revealed that the vast majority of neutrophils in denervated muscle were of the CXCR2 subtype and were recruited by CXCL1. Most of these cells gradually disappeared within 1 week via P53-mediated apoptosis. Experiments using specific blockers confirmed that neutrophils slow the process of denervated muscle atrophy. Collectively, these results indicate that activated neutrophils are recruited via chemotaxis to muscle tissue that has been indirectly damaged by denervation, where they function in delaying atrophy.