The role of hydrogen sulfide regulation of ferroptosis in different diseases.

Ferroptosis is a programmed cell death that relies on iron and lipid peroxidation. It differs from other forms of programmed cell death such as necrosis, apoptosis and autophagy. More and more evidence indicates that ferroptosis participates in many types of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, cardiovascular diseases and so on. Hence, clarifying the role and mechanism of ferroptosis in diseases is of great significance for further understanding the pathogenesis and treatment of some diseases. Hydrogen sulfide (H2S) is a colorless and flammable gas with the smell of rotten eggs. Many years ago, H2S was considered as a toxic gas. however, in recent years, increasing evidence indicates that it is the third important gas signaling molecule after nitric oxide and carbon monoxide. H2S has various physiological and pathological functions such as antioxidant stress, anti-inflammatory, anti-apoptotic and anti-tumor, and can participate in various diseases. It has been reported that H2S regulation of ferroptosis plays an important role in many types of diseases, however, the related mechanisms are not fully clear. In this review, we reviewed the recent literature about the role of H2S regulation of ferroptosis in diseases, and analyzed the relevant mechanisms, hoping to provide references for future in-depth researches.

Exploring Stem-Cell-Based Therapies for Retinal Regeneration.

The escalating prevalence of retinal diseases-notably, age-related macular degeneration and hereditary retinal disorders-poses an intimidating challenge to ophthalmic medicine, often culminating in irreversible vision loss. Current treatments are limited and often fail to address the underlying loss of retinal cells. This paper explores the potential of stem-cell-based therapies as a promising avenue for retinal regeneration. We review the latest advancements in stem cell technology, focusing on embryonic stem cells (ESCs), pluripotent stem cells (PSCs), and mesenchymal stem cells (MSCs), and their ability to differentiate into retinal cell types. We discuss the challenges in stem cell transplantation, such as immune rejection, integration into the host retina, and functional recovery. Previous and ongoing clinical trials are examined to highlight the therapeutic efficacy and safety of these novel treatments. Additionally, we address the ethical considerations and regulatory frameworks governing stem cell research. Our analysis suggests that while stem-cell-based therapies offer a groundbreaking approach to treating retinal diseases, further research is needed to ensure long-term safety and to optimize therapeutic outcomes. This review summarizes the clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt's disease.

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study.

Background: Numerous investigations have suggested links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs), but causality has not been proven. This study used Mendelian randomization (MR) to investigate the causal associations between 91 CIPs and cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), spinal canal stenosis (SCS), and spondylolisthesis/spondylolysis. Methods: Genetic variants data for CIPs and SDDs were obtained from the genome-wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary method, analyzing the validity and robustness of the results through pleiotropy and heterogeneity tests and performing reverse MR analysis to test for reverse causality. Results: The IVW results with Bonferroni correction indicated that beta-nerve growth factor (ß-NGF), C-X-C motif chemokine 6 (CXCL6), and interleukin-6 (IL-6) can increase the risk of CS. Fibroblast growth factor 19 (FGF19), sulfotransferase 1A1 (SULT1A1), and tumor necrosis factor-beta (TNF-ß) can increase PD/SD risk, whereas urokinase-type plasminogen activator (u-PA) can decrease the risk of PD/SD. FGF19 and TNF can increase SCS risk. STAM binding protein (STAMBP) and T-cell surface glycoprotein CD6 isoform (CD6 isoform) can increase the risk of spondylolisthesis/spondylolysis, whereas monocyte chemoattractant protein 2 (MCP2) and latency-associated peptide transforming growth factor beta 1 (LAP-TGF-ß1) can decrease spondylolisthesis/spondylolysis risk. Conclusions: MR analysis indicated the causal associations between multiple genetically predicted CIPs and the risk of four SDDs (CS, PD/SD, SCS, and spondylolisthesis/spondylolysis). This study provides reliable genetic evidence for in-depth exploration of the involvement of CIPs in the pathogenic mechanism of SDDs and provides novel potential targets for SDDs.

[Comparative analysis of the results of microdiscectomy and minimally invasive transforaminal lumbar interbody fusion in the treatment of adjacent-level intervertebral disc herniations with lumbosacral transitional vertebra in elderly patients.]

The purpose of the study was a comparative analysis the effectiveness of microsurgical discectomy and minimally invasive transforaminal lumbar interbody fusion in the treatment of disk herniation adjacent to the anomaly of the lumbosacral junction segment in elderly patients. The study included 80 elderly patients (over 60 years old), divided into two groups: the 1st-(n=39) who underwent microsurgical discectomy; the 2nd- patients (n=41) operated on using minimally invasive transforaminal interbody fusion and percutaneous transpedicular stabilization (MI-TLIF). For the comparative analysis, we used gender characteristics (gender, age), constitutional characteristics (BMI), degree of physical status according to ASA, intraoperative parameters of interventions and the specificity of postoperative patient management, clinical data, and the presence of complications. Long-term outcomes were assessed at a minimum follow-up of 3 years. As a result, it was found that the use of MI-TLIF allows achieving better long-term clinical outcomes, fewer major complications in comparison with the microsurgical discectomy technique in the treatment of disc herniation adjacent to the anomaly of the lumbosacral junction segment in elderly patients.

Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction.

Retinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.

Targeting lysosomal quality control as a therapeutic strategy against aging and diseases.

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

The role of the greater trochanter pain syndrome in lumbar degenerative disc disease surgery.

PURPOSE: Greater trochanter pain syndrome (GTPS) is highly discussed during spine surgeons, accompanies lumbar pain and complicates differential diagnosis. The aim is to raise awareness among physicians and demonstrate the lumbar spine degenerative diseases (LSDD) association with GTPS. METHODS: A retro-prospective analysis enrolled 172 patients with LSDD with GTPS signs. Group I - retrospective (n = 112), group II - prospective (n = 60). Patients of group II with the confirmed diagnosis clinically and by the ultrasound recieved a GCS injection (Betamethasone 2 mg\ml + 5 mg\ml - 1.0). Also the VAS, X-ray and SPSS Statistics package were used. RESULTS: 112 patients in group I, 89 (79.5%) had increased pain in the hip early postOp to 7.8 points by VAS. All patients required trigger point injections of GCS and 68 (77%) received a repeat injection. 76 from 112 patients were tracked for long-term results, and recurrence of GTPS was detected in five people who treated conservatively for three months without dynamics. They were identified GTPS by ultrasound. During the injection, 39 from 43 (90%) patients noted pain reduction to 2.1 by VAS, but symptoms of radiculopathy or spinal stenosis persisted. Two patients (5%) did not note any changes. Two patients (5%) noted complete pain regression and refused the surgery. CONCLUSION: Timely detection of GTPS among spinal surgeons influences tactics and, in some cases, allows one to avoid unnecessary surgical interventions. In turn, ignoring the symptoms of GTPS in the preoperative period can lead to pain intensification in the greater trochanter after surgery for degenerative diseases of the spine.

Comparing the Efficacy and Safety of Unilateral Biportal Endoscopic Decompression with Percutaneous Endoscopic Lumbar Decompression for Lumbar Degenerative Diseases: A Meta-Analysis.

OBJECTIVE: Unilateral biportal endoscopic decompression (UBED) offers the advantages of minimal tissue damage, operational flexibility, and clear visualization, positioning it as an innovative and minimally invasive endoscopic technique. Nevertheless, the clinical evidence supporting the use of UBED in the treatment of degenerative lumbar diseases is limited and conflicting. METHODS: As of October 1, 2023, a comprehensive search was conducted across databases including Web of Science, PubMed, Embase, and the Cochrane Library to identify all published studies on minimally invasive UBED for the treatment of degenerative lumbar diseases. Data pertaining to patient demographics, fluoroscopy time, operative duration, intraoperative hemorrhage, hospitalization length, visual analog scale (VAS) score for back and leg pain, MacNab criteria, Oswestry Disability Index (ODI), and complication rates were extracted. The Newcastle-Ottawa scale was utilized to assess the quality. RESULTS: Twelve articles were included, involving 816 patients. The back VAS score (95% confidence interval [CI]: -0.09-0.07, P = 0.75), MacNab criteria (95% CI: 0.52-2.3, P = 0.82), fluoroscopy time (95% CI: -7.03 to -0.4, P = 0.08), and the incidence of complications (95% CI: 0.5-1.73, P = 0.82) were not significantly different, while the leg VAS score (95% CI: 0.01-0.18, P = 0.03), ODI score (95% CI: -1.03 to -0.09, P = 0.02), operation time (95% CI: 5.76-20.62, P = 0.0005), hospitalization length (95% CI: 0.41-2.76, P = 0.008), and intraoperative hemorrhage (95% CI: 21.92-72.44, P = 0.0003) were significantly different. CONCLUSIONS: UBED offers superiority in ODI, flexibility, and visual field clarity. Conversely, percutaneous endoscopic lumbar decompression presents advantages in terms of operation duration, blood loss, hospitalization length, and leg VAS score. These factors should be thoroughly considered when selecting a surgical approach.

Surgical tactics of two-segmental cervical degenerative diseases: risk factors retrospective assessment and preoperative planning.

Background: Currently, in the specialized literature there are no substantiated clinical and radiological indications for differentiated use of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) in the treatment of patients with two-segmental cervical degenerative diseases. The objectives of this study were to (I) identify risk factors that were associated with unsatisfactory results of two-level ACDF and one-level ACCF in the treatment of patients with cervical degenerative diseases despite current perioperative management, and (II) develop a clinical and radiological algorithm for personalized surgical tactics. Methods: We retrospectively identified risk factors for the development of unsatisfactory clinical postoperative results after two-level ACDF (n=81) and one-level ACCF (n=78), operated in the period of 2009-2019 for two-segmental cervical degenerative disease. Results: Satisfactory clinical results after two-level ACDF were noted in cases with total kyphotic deformity of less than 15°; local kyphotic deformity less than 10˚; the absence of circumferential spondylotic cervical stenosis; the absence of a myelopathic lesion at the level of the vertebral body; absence of migrating intervertebral disk (IVD) hernia more than 1/3 of the vertebral body; T1 slope vertebra less than 15°; IVD degeneration according to Suzuki A. 0-II; facet joint (FJ) degeneration according to Okamoto A. I-III; interbody height (IH) more than 2 mm. Satisfactory clinical results after single-level ACCF were registered in cases with IVD degeneration according to Suzuki A. III; FJ degeneration according to Okamoto A. IV-V; IH 3 mm or less; regardless of the cervical lordosis, the angle of local kyphotic deformity and T1 slope, the presence of circumferential spondylotic cervical stenosis, the localization of the myelopathic lesion and the distance of migration IVD herniation. Conclusions: Individual planning and differentiated implementation of ACDF and ACCF in patients with two-segmental cervical degenerative disease, taking into account a comprehensive preoperative clinical and radiological assessment, contributes to the effective elimination of existing neurological symptoms, reducing the intensity of neck pain and upper limbs pain, restoring the functional state and quality of patients' lives in the minimum 24 months postoperative period, as well as reducing the number of postoperative complications and reoperations.

Regenerative treatment of ophthalmic diseases with stem cells: Principles, progress, and challenges.

Background: Degenerate eye disorders, such as glaucoma, cataracts and age-related macular degeneration (AMD), are prevalent causes of blindness and visual impairment worldwide. Other eye disorders, including limbal stem cell deficiency (LSCD), dry eye diseases (DED), and retinitis pigmentosa (RP), result in symptoms such as ocular discomfort and impaired visual function, significantly impacting quality of life. Traditional therapies are limited, primarily focus on delaying disease progression, while emerging stem cell therapy directly targets ocular tissues, aiming to restore ocular function by reconstructing ocular tissue. Main text: The utilization of stem cells for the treatment of diverse degenerative ocular diseases is becoming increasingly significant, owing to the regenerative and malleable properties of stem cells and their functional cells. Currently, stem cell therapy for ophthalmopathy involves various cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells (RPCs). In the current article, we will review the current progress regarding the utilization of stem cells for the regeneration of ocular tissue covering key eye tissues from the cornea to the retina. These therapies aim to address the loss of functional cells, restore damaged ocular tissue and or in a paracrine-mediated manner. We also provide an overview of the ocular disorders that stem cell therapy is targeting, as well as the difficulties and opportunities in this field. Conclusions: Stem cells can not only promote tissue regeneration but also release exosomes to mitigate inflammation and provide neuroprotection, making stem cell therapy emerge as a promising approach for treating a wide range of eye disorders through multiple mechanisms.

Small extracellular vesicles of organoid-derived human retinal stem cells remodel Müller cell fate via miRNA: A novel remedy for retinal degeneration.

Remodeling retinal Müller glial fate, including gliosis inhibition and pro-reprogramming, represents a crucial avenue for treating degenerative retinal diseases. Stem cell transplantation exerts effects on modulating retinal Müller glial fate. However, the optimized stem cell products and the underlying therapeutic mechanisms need to be investigated. In the present study, we found that retinal progenitor cells from human embryonic stem cell-derived retinal organoids (hERO-RPCs) transferred extracellular vesicles (EVs) into Müller cells following subretinal transplantation into RCS rats. Small EVs from hERO-RPCs (hERO-RPC-sEVs) were collected and were found to delay photoreceptor degeneration and protect retinal function in RCS rats. hERO-RPC-sEVs were taken up by Müller cells both in vivo and in vitro, and inhibited gliosis while promoting early dedifferentiation of Müller cells. We further explored the miRNA profiles of hERO-RPC-sEVs, which suggested a functional signature associated with neuroprotection and development, as well as the regulation of stem cell and glial fate. Mechanistically, hERO-RPC-sEVs might regulate the fate of Müller cells by miRNA-mediated nuclear factor I transcription factors B (NFIB) downregulation. Collectively, our findings offer novel mechanistic insights into stem cell therapy and promote the development of EV-centered therapeutic strategies.

The Effect of Unintended Facet Arthrodesis on the Treatment Outcome of Dynamic Neutralization System for Lumbar Degenerative Diseases.

Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.

Longitudinal Study on Pre- and Post-Operation CT Imaging for Predicting Pedicle Screw Loosening in Patients with Lumbar Degenerative Disease.

Purpose: We conducted a longitudinal study to examine the predictive role of risk factors in the occurrence of pedicle screw loosening, assessed through pre- and post-operative computed tomography (CT) scans. Methods: A total of 103 patients with degenerative lumbar disease who had undergone L4/5 pedicle screw fixation (involving 412 screws) were included in this study. They were subsequently categorized into two groups-the "loosening group" and the "non-loosening group". The axial and sagittal angles of the screw trajectory in pre- and post-operative CT images were measured, and the deviation angles were computed. Additionally, measurements were taken of the Hounsfield unit (HU) within the screw entry point area, the pedicle, and the vertebral body in preoperative CT images. Logistic regression analysis was employed to ascertain the risk factors influencing the occurrence of screw loosening. Results: Elderly patients who experienced screw loosening tended to have bilateral screw issues at the L5 level (p < 0.005). The HU of the pedicle (p < 0.001), age (p < 0.001), and the axial deviation angle (p = 0.014) were identified as independent factors predicting screw loosening. Additionally, when HU of the pedicle < 126.5 or age ≥ 53.5 years, the axial deviation angle was found to be smaller in the group experiencing screw loosening (p = 0.018 and p = 0.019). Conclusion: Loosening of screws positioned at L5 was found to be more prevalent in elderly patients, particularly exhibiting a bilateral occurrence. Independent predictors of this phenomenon included a low HU value in the pedicle, advanced age in patients, and a substantial axial deviation angle. In the case of elderly patients with a low HU value in the pedicle, a reduced axial surgical deflection was necessitated to prevent the occurrence of screw loosening.

Analysis of Factors Associated with Lumbar Degenerative Disease Complicated by Baastrup's Disease.

OBJECTIVE: To investigate the factors associated with the occurrence of Baastrup's disease (BA) in patients with lumbar degenerative diseases (LDDs). METHODS: A retrospective analysis was conducted on 168 patients with LDDs (including lumbar disc herniation, lumbar spinal stenosis, and lumbar spondylolisthesis) who were treated at our hospital from January 2020 to January 2023, comprising 95 males and 73 females, aged 48-84 years.Patients were divided into two groups based on the presence of Baastrup's disease: those with BA (Group A) and those without BA (Group B).Relevant patient factors were extracted, including age, gender, occupation, smoking history, alcohol consumption history, body mass index, bone density, presence of internal diseases (diabetes, hypertension), lumbar lordosis angle, endplate Modic changes, degree of intervertebral disc degeneration, and facet joint degeneration (Weishaupt grading).Statistical analysis was performed using, Statistical Package for the Social Sciences 26.0 software to compare the differences in these factors between the two groups, and statistically significant results were included in a multivariate logistic regression analysis. RESULTS: Univariate analysis indicated that there were no statistically significant differences between the two groups in terms of gender, smoking history, alcohol consumption history, bone density, presence of internal diseases (diabetes, hypertension), lumbar lordosis angle, and endplate Modic changes (P>0.05),whereas age, occupation, body mass index, degree of intervertebral disc degeneration, and degree of facet joint degeneration showed statistically significant differences (P < 0.05).Multivariate logistic regression analysis revealed that age, degree of intervertebral disc degeneration, and degree of facet joint degeneration were independent risk factors for the occurrence of BA in patients with LDDs (P < 0.05). CONCLUSIONS: BA is relatively common in patients with LDDs, and advanced age, severe intervertebral disc degeneration, and facet joint degeneration are its independent risk factors.

First-In-Human Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of AZP2006, A Synthetic Compound for the Treatment of Alzheimer's Disease and Related Diseases.

Background: Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are major neurodegenerative conditions with tau pathology in common but distinct symptoms-AD involves cognitive decline while PSP affects balance and eye movement. Progranulin (PGRN) is a growth factor implicated in neurodegenerative diseases, including AD and PSP. AZP2006, a synthetic compound, targets tauopathies by stabilizing PGRN levels and reducing tau aggregation and neuroinflammation. Objective: Evaluate the safety, tolerability, and pharmacokinetics of AZP2006. Methods: A first-in-Human phase 1 study comprised a single ascending dose (SAD) and a multiple ascending dose study (MAD). The SAD study included 64 healthy male volunteers and tested singles oral doses of 3 to 500 mg of AZP2006 free base equivalent or placebo. In the MAD study, 24 healthy male volunteers were administered oral doses of 30, 60, and 120 mg per day of AZP2006 or placebo for 10 days. Results: No serious adverse events were observed. Clinical, biological, and electrocardiogram findings were non-relevant. Nineteen minor adverse events resolved before study completion. The safety profile indicated no specific risks. The multiple ascending dose study was halted, and the optional dose level of 180 mg was not performed due to high levels of M2 metabolite in plasma that necessitated additional preclinical evaluation of M2. Both AZP2006 and its M2 metabolite were quickly absorbed and widely distributed in tissues. Exposure increased more than proportionally with dose. Conclusions: AZP2006 had a favorable safety profile and was rapidly absorbed. Elevated M2 metabolite levels necessitated further studies to clarify excretion and metabolism mechanisms.

Prospective Randomized Comparison of Minimally Invasive Tlif versus Open Tlif: Clinical Effectiveness and Restoration of Working Capacity in Railway Workers.

STUDY DESIGN: Randomized Clinical Trial. OBJECTIVE: To compare the clinical efficacy and restoration of working capacity after MI (minimally invasive)-TLIF and O (open)-TLIF in railway workers with lumbar degenerative disease. METHODS: 83 patients, who were indicated for two-level lumbar decompression and fusion were randomly assigned to one of two groups: group 1 (n = 44) had MI-TLIF procedure and group 2 (n = 39) had O-TLIF procedure. The functional status was assessed using SF-36, ODI and VAS for back and leg pain, preoperatively, at discharge, and at 3, 6, and 12 months postoperatively. MRI and CT were obtained 1-year follow-up. The percentage of patients who returned to work at 1-year, work intensity and the time to return to work post-operatively were analyzed. RESULTS: At 1-year follow-up, the MI-TLIF group had significantly better ODI, VAS and SF-36 scores compared to the O-TLIF group. The postoperative MRIs revealed a statistically significantly less multifidus muscle atrophy in the MI group compared to the Open group. At 1-year follow-up, a comparable fusion ratio between MI group and Open group was recorded. After MI-TLIF procedure, depending on the workload, patients had a statistically significantly earlier return to work (P < .05) and statistically significantly higher return to work rate compared with the O-TLIF group (P < .05). CONCLUSIONS: The use of two-level MI-TLIF in railway workers has made it possible to significantly improve long-term clinical results, reduce the risk of surgical complications, muscle atrophy and time to return to work compared to O-TLIF.

Compounding engineered mesenchymal stem cell-derived exosomes: A potential rescue strategy for retinal degeneration.

The prevalence of retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, has been increasing globally and is linked to the aging population and improved life expectancy. These diseases are characterized by chronic, progressive neuronal damage or depletion of the photoreceptor cells in the retina, and limited effective treatment options are currently available. Mesenchymal stem cell-derived exosomes (MSC-EXOs) containing cytokines, growth factors, lipids, mRNA, and miRNA, which act as mediators of intercellular communication transferring bioactive molecules to recipient cells, offer an appealing, non-cellular nanotherapeutic approach for retinal degenerative diseases. However, treatment specificity is compromised due to their high heterogeneity in size, content, functional effects, and parental cellular source. To improve this, engineered MSC-EXOs with increased drug-loading capacity, targeting ability, and resistance to bodily degradation and elimination have been developed. This review summarizes the recent advances in miRNAs of MSC-EXOs as a treatment for retinal degeneration, discussing the strategies and methods for engineering therapeutic MSC-EXOs. Notably, to address the single functional role of engineered MSC-EXOs, we propose a novel concept called "Compound Engineered MSC-EXOs (Co-E-MSC-EXOs)" along with its derived potential therapeutic approaches. The advantages and challenges of employing Co-E-MSC-EXOs for retinal degeneration in clinical applications, as well as the strategies and issues related to them, are also highlighted.

Early result of percutaneous full-endoscopic transforaminal lumbar interbody fusion in the treatment of single-level lumbar degenerative diseases: a retrospective study.

OBJECTIVE: The study aimed to evaluate the short-term clinical efficacy of percutaneous full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) for lumbar degenerative diseases (LDD). METHODS: From July 2020 to July 2021, 93 patients who underwent single-level lumbar fusion procedure were retrospective analysis. The patients were divided into Endo-TLIF group and transforaminal lumbar interbody fusion (TLIF) group. General demographic and perioperative data were recorded, the clinical outcomes were evaluated using visual analogue scale (VAS) and oswestry disability index (ODI). The disk height (DH) was compared between the two groups. RESULTS: All of the surgical procedures were successfully completed, and the patients were followed for a minimum of 2 years. Intraoperative blood loss, drainage volume, time to independent ambulation and hospital length of stay in the Endo-TLIF group were significantly decreased in comparison with the open TLIF group (p < 0.05). The VAS for back pain on postoperative 7 day and ODI on postoperative 1 month were lower in the Endo-TLIF group than in the open TLIF group (P < 0.05), but no significant difference at 1 year and 2 years postoperatively (P > 0.05). The VAS score of leg pain had no demographic statistically significant differences between the groups (P > 0.05). The DH were significantly heightened after surgery compared to the preoperative height (p < 0.05). CONCLUSION: Endo-TLIF is a minimally invasive, safety surgery which can achieve comparable short-term effects as open TLIF. It may be a promising option for the treatment of LDD.

A Comprehensive Review of Therapeutic Compounds from Plants for Neurodegenerative Diseases.

Neurodegenerative diseases (NDDs) comprise a large number of disorders that affect the structure and functions of the nervous system. The major cause of various neurodegenerative diseases includes protein aggregation, oxidative stress and inflammation. Over the last decade, there has been a gradual inclination of neurological research in order to find drugs that can prevent, slow down, or treat these diseases. The most common NDDs are Alzheimer's, Parkinson's, and Huntington's illnesses which claims the lives of 6.8 million people worldwide each year and it is expected to rise by 7.1%. The focus on alternative medicine, particularly plant-based products, has grown significantly in recent years. Plants are considered a good source of biologically active molecules and hence phytochemical screening of plants will pave the way for discovering new drugs. Neurodegeneration has long been linked to oxidative stress, either as a direct cause or as a side effect of other variables. Therefore, it has been proposed that the use of antioxidants to combat cellular oxidative stress within the nervous system may be a viable therapeutic strategy for neurological illnesses. In order to prevent and treat NDDs, this review article covers the therapeutic compounds/ metabolites from plants with the neuroprotective role. However, these exhibit other beneficial molecular functions in addition to antioxidant activity is the potential application in the management or prevention of neurodegenerative disorders. Further, it gives future researchers the significance of considering peptide-based therapeutics through various mechanisms in delaying or curing neurodegenerative diseases.

Development of an International AO Spine Guideline for the Use of Osteobiologics in Anterior Cervical Fusion and Decompression (AO-GO).

STUDY DESIGN: Methodological study for guideline development. OBJECTIVE: AO Spine Guideline for Using Osteobiologics (AO-GO) project for spine degenerative pathologies was an international, multidisciplinary collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in Anterior Cervical Fusion and Decompression (ACDF). The aim was to formulate precisely defined, clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics, considering regional preferences and cost-effectiveness. METHODS: Guideline was completed in two phases: Phase 1- evidence synthesis; Phase 2- recommendation development based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In Phase 1, key questions identified by a panel of experts were addressed in a series of systematic reviews of randomized and non-randomized studies. In Phase 2, the GRADE approach was used to formulate a series of recommendations, including expert panel discussions via web calls and face-to-face meetings. DISCUSSION: AO-GO aims to bridge an important gap between evidence and use of osteobiologics in spine fusion surgeries. Owing to differences in osteobiologics preparation and functional characteristics, regulatory requirements for approval may vary, therefore it is highly likely that these products enter market without quality clinical trials. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making processes in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries. In Phase 3, the guideline will be disseminated and validated using prospectively collected clinical data in a separate effort of the AO Spine Knowledge Forum Degenerative in a global multicenter clinical study.