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Purpose: The purpose of this study was to compare the clinical efficacy of foldable capsular vitreous body (FCVB) filled with either light or heavy silicone oil and the incidence of complications after their implantation for the treatment of severe ocular trauma and silicone oil-dependent eyes. Methods: FCVB filled with either light (n = 16) or heavy (n = 8) silicone oil was implanted in 24 patients. During the 12-month follow-up period, the intraocular pressure, final best-corrected visual acuity, retinal reattachment condition, position of the FCVB, and complications were assessed. Results: All surgeries were performed without issue. There was no significant difference in preoperative and postoperative best-corrected visual acuity between the two groups. A significant improvement in the intraocular pressure was observed after surgery in both the light silicone oil (P = 0.029) and heavy silicone oil (P = 0.035) groups. None of the patients developed displacement or prolapse of the FCVB. The most common early and late postoperative complications were postoperative hemorrhage (33.3%) and corneal opacification (50%), respectively. Conclusions: FCVB filled with heavy silicone oil can be used as a supplemental therapy for patients who have lost the anterior segment of their eye, have lesions of the inferior retina, or cannot maintain the prone position for various reasons. Translational Relevance: Implantation of FCVB combined with heavy silicone oil compensates for the shortcomings of this with light silicone oil, providing patients with more personalized treatment.
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Huiles de silicone , Acuité visuelle , Corps vitré , Humains , Huiles de silicone/usage thérapeutique , Huiles de silicone/effets indésirables , Mâle , Femelle , Adulte , Corps vitré/effets des médicaments et des substances chimiques , Adulte d'âge moyen , Acuité visuelle/effets des médicaments et des substances chimiques , Résultat thérapeutique , Jeune adulte , Vitrectomie/effets indésirables , Vitrectomie/méthodes , Pression intraoculaire/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Décollement de la rétine/chirurgie , Adolescent , Prothèses et implants/effets indésirables , Études de suivi , Complications postopératoires/étiologie , Sujet âgé , Tamponnement interne/méthodesRÉSUMÉ
PURPOSE: Current research suggests that oxidative stress may decrease bone mineral density (BMD) by disrupting bone metabolism balance. However, no study investigated the relationship between systemic oxidative stress status and adult BMD. This study aims to investigate whether oxidative balance score (OBS) is associated with BMD in adults under 40. METHODS: 3963 participants were selected from the National Health and Nutrition Survey (NHANES) from 2011 to 2018. OBS is scored based on 20 dietary and lifestyle factors. Weighted multiple logistic regression and restricted cubic splines were used to assess the correlation between OBS and osteopenia. RESULTS: After adjusting for confounding factors, the weighted logistic regression results showed that compared with the first tertile of OBS, the highest tertile had a 38% (OR: 0.62, 95% CI: 0.47-0.82) lower risk of osteopenia. The restrictive cubic spline curve indicates a significant nonlinear correlation between OBS and the risk of osteopenia. CONCLUSION: The research findings emphasize the relationship between OBS and the risk of osteopenia in young adults. Adopting an antioxidant diet and lifestyle may help young adults to maintain bone mass.
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Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.
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Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single-cell sequencing is then performed. According to time-series sample comparison, transplanted cells mainly undergo neural development at 2 months post-transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine.
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Organoïdes , Transcriptome , Humains , Organoïdes/métabolisme , Organoïdes/cytologie , Organoïdes/transplantation , Transcriptome/génétique , Encéphale/métabolisme , Analyse sur cellule unique/méthodes , Différenciation cellulaire/génétique , Cortex préfrontal/métabolisme , Cortex préfrontal/cytologie , Hippocampe/métabolismeRÉSUMÉ
OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.
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Discectomie percutanée , Endoscopie , Déplacement de disque intervertébral , Vertèbres lombales , Réintervention , Humains , Déplacement de disque intervertébral/chirurgie , Adolescent , Études rétrospectives , Mâle , Femelle , Vertèbres lombales/chirurgie , Discectomie percutanée/méthodes , Endoscopie/méthodes , Jeune adulteRÉSUMÉ
Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.
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Adénine/analogues et dérivés , Dégénérescence de disque intervertébral , Disque intervertébral , Nucleus pulposus , Humains , Dégénérescence de disque intervertébral/métabolisme , Disque intervertébral/métabolisme , Nucleus pulposus/métabolisme , Autophagie , Apoptose , MéthylationRÉSUMÉ
@#Objective To propose a heart sound segmentation method based on multi-feature fusion network. Methods Data were obtained from the CinC/PhysioNet 2016 Challenge dataset (a total of 3 153 recordings from 764 patients, about 91.93% of whom were male, with an average age of 30.36 years). Firstly the features were extracted in time domain and time-frequency domain respectively, and reduced redundant features by feature dimensionality reduction. Then, we selected optimal features separately from the two feature spaces that performed best through feature selection. Next, the multi-feature fusion was completed through multi-scale dilated convolution, cooperative fusion, and channel attention mechanism. Finally, the fused features were fed into a bidirectional gated recurrent unit (BiGRU) network to heart sound segmentation results. Results The proposed method achieved precision, recall and F1 score of 96.70%, 96.99%, and 96.84% respectively. Conclusion The multi-feature fusion network proposed in this study has better heart sound segmentation performance, which can provide high-accuracy heart sound segmentation technology support for the design of automatic analysis of heart diseases based on heart sounds.
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Objective: To investigate the value of ultrasonography as a diagnostic aid in differentiating intramuscular capillary-type hemangioma (ICTH) from fibro-adipose vascular anomaly (FAVA). Methods: A retrospective analysis was conducted of the clinical and ultrasound imaging data of 20 patients with ICTH and 45 patients with FAVA who were admitted to and pathologically confirmed in hospital between January 2013 and April 2023. The clinical and ultrasonographic appearances of the lesions in the two groups were compared and analyzed. A stepwise regression analysis was performed, and a joint diagnostic equation was constructed using the final variables selected. The receiver operating characteristic (ROC) curve and indicators, including sensitivity and specificity, were used to evaluate the efficacy of the joint diagnostic model. Results: The two groups of patients suffering from ICTH and FAVA presented a statistically significant difference (P< 0.05) in terms of 'age', 'lesion size', 'fascial tail sign', 'presence of a fatty-tissue-like hyperecho around the lesion', 'blood flow' and 'presence of straight blood capillaries within the lesion'. Finally, the variables 'fascial tail sign' and 'presence of straight blood capillaries within the lesion' were selected to construct the model. The constructed joint diagnostic model had a sensitivity value of 70.0% (95% CI: 59.00-81.00), a specificity value of 98.0% (95% CI: 94.70-100.00) and a ROC curve value of 0.908, indicating the high efficacy of the combined diagnosis method. Conclusions: Ultrasonography can be utilized to differentiate ICTH from FAVA, and the combined diagnosis method can further improve the technique's diagnostic efficacy.
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Objective: To review the clinical research progress of spinal epidural lipomatosis (SEL). Methods: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. Results: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. Conclusion: SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.
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Lipomatose , Maladies de la moelle épinière , Humains , Décompression chirurgicale/méthodes , Espace épidural/anatomopathologie , Espace épidural/chirurgie , Lipomatose/diagnostic , Lipomatose/chirurgie , Imagerie par résonance magnétique , Maladies de la moelle épinière/chirurgieRÉSUMÉ
Although numerous studies have shown distinctive similarities between osteomyelitis and diabetic foot ulcers (DFU), the common pathogenesis of both is not fully understood. The current research focuses on an in-depth study of the molecular and pathway mechanisms involved in the complication of these 2 diseases. We downloaded clinical information on osteomyelitis (GSE30119) and DFU (GSE29221) from the GEO database, along with gene expression matrices. Differentially expressed genes (DEGs) among normal individuals and patients with osteomyelitis; normal individuals and patients with DFU were identified by R software, and thus common DEGs were confirmed. We then analyzed these differential genes, including the functional pathway analysis, protein-protein interaction (PPI), modules and hub genes establishment, and transcription factor regulatory networks. We identified 109 common DEGs (46 up-regulated and 63 down-regulated genes) for subsequent analysis. The results of PPI network and the functional pathway analysis revealed the importance of immune response and inflammatory response in both diseases. Among them, chemokines and cytokines were found to be closely related to both osteomyelitis and DFU. In addition, the tumor necrosis factor (TNF) pathway and Staphylococcus aureus infection were found to have more significant roles too. The 12 most essential key genes were later screened by cytoHubba, including matrix metalloproteinases (MMP) 1, MMP3, MMP9, IL8, C-X-C chemokine receptor (CXCR) 2, C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL13, FCGR3B, IL1B, LCN2, S100A12. CXCL10, and MMP1 were validated using the least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Osteomyelitis and DFU share similar molecular and pathway mechanisms. These common key genes and pathways may provide new directions toward the future study of osteomyelitis and DFU.
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Diabète , Pied diabétique , Ostéomyélite , Humains , Analyse de profil d'expression de gènes/méthodes , Réseaux de régulation génique , Pied diabétique/génétique , Analyse sur microréseau , Ostéomyélite/génétique , Biologie informatique/méthodesRÉSUMÉ
Ferroptosis has been proven critical for survival following bone marrow mesenchymal stem cells (BMSCs) explantation. Suppression of ferroptosis in BMSCs will be a valid tactic to elevate the therapeutic potential of engrafted BMSCs. Prominin2 is a pentaspanin protein involved in mediating iron efflux and thus modulates resistance to ferroptosis, but its role in tert-butyl hydroperoxide (TBHP)-induced BMSCs ferroptosis remains elusive. We examined the biological effect of prominin2 in vitro and in vivo by using cell proliferation assay, iron assay, reactive oxygen species (ROS) examination, malondialdehyde assay, glutathione (GSH) examination, Western blot, quantitative reverse transcription-PCR, immunofluorescence staining assay, gene expression inhibition and activation, co-immunoprecipitation (CO-IP) assay, radiographic analysis, and histopathological analysis. Our study demonstrated that prominin2 activity was impaired in TBHP-induced BMSCs ferroptosis. We found that PROM2 (encoding the protein prominin2) activation delayed the onset of ferroptosis and PROM2 knockdown deteriorated the course of ferroptosis. CO-IP, Western blot, and immunofluorescence demonstrated that prominin2 exerts antiferroptosis effects by inhibiting BTB and CNC homology 1 (BACH1) that promotes ROS generation, and thus exerts potent antioxidant effects in oxidative stress (OS)-induced BMSCs ferroptosis, including elevating BMSCs' survival rate and enhancing GSH contents. BMSCs with PROM2 overexpression also partially delayed the progression of intervertebral disk degeneration in vivo, as illustrated by less loss of disk height and lower histological scores. Our findings revealed a mechanism that the prominin2/BACH1/ROS axis participates in BMSCs ferroptosis and the strengthening of this axis is promising to maintain BMSCs' survival after explantation.NEW & NOTEWORTHY We found that prominin2 might be a potential biomarker and is expected to be utilized to augment engrafted bone marrow mesenchymal stem cells (BMSCs) survival rate. The prominin2/BTB and CNC homology 1 (BACH1)/reactive oxygen species (ROS) axis, which participates in the regulation of BMSCs ferroptosis induced by tert-butyl hydroperoxide (TBHP), is uncovered in our study. The therapeutic targeting of the prominin2/BACH1/ROS axis components is promising to elevate the survival of transplanted BMSCs in clinical practice.
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Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.
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Ferroptose , Surcharge en fer , Transplantation de cellules souches mésenchymateuses , Cellules souches mésenchymateuses , Humains , Antioxydants/métabolisme , Surcharge en fer/métabolismeRÉSUMÉ
@#Objective To explore the application of Tsetlin Machine (TM) in heart beat classification. Methods TM was used to classify the normal beats, premature ventricular contraction (PVC) and supraventricular premature beats (SPB) in the 2020 data set of China Physiological Signal Challenge. This data set consisted of the single-lead electro-cardiogram data of 10 patients with arrhythmia. One patient with atrial fibrillation was excluded, and finally data of the other 9 patients were included in this study. The classification results were then analyzed. Results The classification results showed that the average recognition accuracy of TM was 84.3%, and the basis of classification could be shown by the bit pattern interpretation diagram. Conclusion TM can explain the classification results when classifying heart beats. The reasonable interpretation of classification results can increase the reliability of the model and facilitate people's review and understanding.
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@#Objective To recognize the different phases of Korotkoff sounds through deep learning technology, so as to improve the accuracy of blood pressure measurement in different populations. Methods A classification model of the Korotkoff sounds phases was designed, which fused attention mechanism (Attention), residual network (ResNet) and bidirectional long short-term memory (BiLSTM). First, a single Korotkoff sound signal was extracted from the whole Korotkoff sounds signals beat by beat, and each Korotkoff sound signal was converted into a Mel spectrogram. Then, the local feature extraction of Mel spectrogram was processed by using the Attention mechanism and ResNet network, and BiLSTM network was used to deal with the temporal relations between features, and full-connection layer network was applied in reducing the dimension of features. Finally, the classification was completed by SoftMax function. The dataset used in this study was collected from 44 volunteers (24 females, 20 males with an average age of 36 years), and the model performance was verified using 10-fold cross-validation. Results The classification accuracy of the established model for the 5 types of Korotkoff sounds phases was 93.4%, which was higher than that of other models. Conclusion This study proves that the deep learning method can accurately classify Korotkoff sounds phases, which lays a strong technical foundation for the subsequent design of automatic blood pressure measurement methods based on the classification of the Korotkoff sounds phases.
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Objective:To compare the clinical efficacy of percutaneous transhepatic gallbladder drainage (PTGBD) combined with delayed laparoscopic cholecystectomy (LC) with direct LC in the treatment of acute cholecystitis.Methods:A single-center case-control retrospective study was used. Sixty-three patients with acute cholecystitis with onset time ≥ 72 hours during the period from August 1, 2021 to December 10, 2022 in the Department of Hepatobiliary Surgery of the 900TH Hospital of Joint Logistics Support Force were selected. There were 38 males and 25 females, aged (57.3±15.4) years, with an age range of 28-87 years. According to whether PTGBD treatment was performed before LC, they were divided into experimental group ( n=29) and control group ( n=34). Experimental group was treated with PTGBD combined with delayed LC and control group was treated with LC only.The differences in operative time, intra-operative bleeding, intra-operative transit open rate, post-operative hospital days, total hospital days, hospital costs, short-term post-operative complications of LC and post-operative time to exhaustion were compared and analysed between the two groups. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups.Measurement data with skewed distribution were expressed as M( Q1, Q3), and rank sum test was used for comparison between groups; Chi-square test was used to compare the counting data groups. Results:Intraoperative bleeding, total hospital days, hospital costs and postoperative time to exhaustion were 0(0, 50) mL, 13(11, 18) d, 29 015.0 (22 791.6, 39 000.8) yuan and 1(1, 2) d in the experimental group and 50(0, 88) mL, 7(6, 11) d, 16 015.0 (15 832.1, 22 185.1) yuan, 2(1, 3) d, the difference was statistically significant between the two groups( P<0.05). In the experimental group, the operative time, the intraoperative transit open rate, the number of postoperative hospital days, and the incidence of short-term postoperative complications of LC were 80 (55, 115) min, 13.8%, 5 (3, 7) days, 34.5%, respectively, compared with 98(70, 125) min, 20.6%, 5(3, 6) days, 38.2% in the control group, the difference between the two groups was not statistically significant ( P>0.05). Conclusion:The clinical efficacy of PTGBD combined with delayed LC is better than direct line LC, and it is feasible and effective for patients with cholecystitis whose inflammatory indexes have returned to normal and who have high gallbladder tone.
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@#Currently, in precision cardiac surgery, there are still some pressing issues that need to be addressed. For example, cardiopulmonary bypass remains a critical factor in precise surgical treatment, and many core aspects still rely on the experience and subjective judgment of cardiopulmonary bypass specialists and surgeons, lacking precise data feedback. With the increasing elderly population and rising surgical complexity, precise feedback during cardiopulmonary bypass becomes crucial for improving surgical success rates and facilitating high-complexity procedures. Overcoming these key challenges requires not only a solid medical background but also close collaboration among multiple interdisciplinary fields. Establishing a multidisciplinary team encompassing professionals from the medical, information, software, and related industries can provide high-quality solutions to these challenges. This article shows several patents from a collaborative medical and electronic information team, illustrating how to identify unresolved technical issues and find corresponding solutions in the field of precision cardiac surgery while sharing experiences in applying for invention patents.
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Microglia, the main immune macrophages in the central nervous system, can be highly involved in the occurrence and development of Alzheimer's disease(AD)through microglia polarization and receptor protein expression. Traditional Chinese Medicine has been demonstrated to have regulatory effects on MG. Many active components in Traditional Chinese herbs play important roles in decreasing β-amyloid peptide(Aβ)accumulation, inhibiting neuro-inflammation and regulating microglia polarization etc. In this study the role of microglia in the pathogenesis of AD and the mechanism by which Traditional Chinese Medicine regulating microglia are reviewed to provide a reference for the treatment of AD.
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Purpose: Polypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment. Methods: We conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response. Results: The results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group. Conclusions: Our study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.
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Cytokines , Facteur de nécrose tumorale alpha , Humains , Études rétrospectives , Molécule-1 d'adhérence des cellules vasculaires , Facteur de croissance endothéliale vasculaire de type A , ChoroïdeRÉSUMÉ
Bone marrow mesenchymal stem cells (BMSCs) have been investigated as cellular therapeutics for intervertebral disc degeneration. However, transplanted BMSCs are prone to be damaged. TNF-α is reported to extensively promote degeneration process. Nevertheless, the relationship between BMSCs senescence and TNF-α-induced stress has not been elucidated. Previous studies showed that mitophagy is a crucial factor in maintaining cellular homeostasis. Hence, we sought to clarify the role and mechanism of mitophagy in TNF-α-induced biological changes of BMSCs. Here, we found that TNF-α caused transient senescent damage in the early stage. Meanwhile, Parkin-mediated mitophagy was initiated and weakened the damage through maintaining mitochondria homeostasis. After inhibiting mitophagy by knockdown of Parkin, TNF-α irreversibly caused cellular senescence. These results suggested that Parkin-mediated mitophagy played protective role in BMSCs in response to TNF-α, which could be a crucial therapeutic target in the future.
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Cellules souches mésenchymateuses , Mitophagie , Apoptose , Cellules de la moelle osseuse , Facteur de nécrose tumorale alpha/pharmacologie , Ubiquitin-protein ligasesRÉSUMÉ
Retinal ganglion cells (RGCs) axons are the signal carriers of visual information between retina and brain. Therefore, they play one of the important roles affected in many optic neurodegenerative diseases like glaucoma. Among the genetic risks associated with glaucoma, the E50K mutation in the Optineurin (OPTN) gene are known to result in glaucoma in the absence of increased intraocular pressure (IOP), whereas the relevant pathological mechanism and neurological issues remain to be further investigated. In this study, the OPTN (E50K) mutant mouse model was established through CRISPR/Cas9-mediated genome editing, and aging-related RGCs loss and the visual dysfunction were identified. In E50K mice 16 months old, the axonal transport decreased comparing to wild-type (WT) mice at the same age. Furthermore, results of electron microscopy demonstrated significant morphological anomaly of mitochondria in RGCs axons of young E50K mice 3 months old, and these changes were aggravated with age. These indicated that the damaged mitochondria-associated dysfunction of RGCs axon should play an etiological role in glaucoma as an age-related outcome of OPTN (E50K) mutation. The findings of this study have potential implications for the targeted prevention and treatment of NTG.