FTH1 protects against osteoarthritis by MAPK pathway inhibition of extracellular matrix degradation.

OBJECTIVE: Ferritin heavy chain 1 (FTH1) is an important subunit of ferro-storing proteins and is indispensable for iron metabolism. Though it has been extensively studied in numerous organs and diseases, the relationship between FTH1 and osteoarthritis (OA) is unclear. DESIGN: Primary murine chondrocytes and cartilage explants were treated with FTH1 siRNA for 72 h. Mice were injected with adenovirus expressing FTH1 after destabilized medial meniscus (DMM) surgery. These approaches were used to determine the effect of FTH1 expression on the pathophysiology of OA. RESULTS: FTH1 expression was down regulated in OA patients and mice after DMM surgery. Knock down of FTH1 induced articular cartilage damage and extracellular matrix degradation in cartilage explants. Further, over expression of FTH1 reduced the susceptibility of chondrocytes to ferroptosis and reversed decrements in SOX9 and aggrecan after DMM surgery. Moreover, FTH1 relieved OA by inhibition of the chondrocyte MAPK pathway. CONCLUSION: This study found FTH1 to play an essential role in extracellular matrix degradation, ferroptosis, and chondrocytes senescence during OA progression. Further, injection of adenovirus expressing FTH1 may be a potential strategy for OA prevention and therapy.

A modular hydrogel bioink containing microsphere-embedded chondrocytes for 3D-printed multiscale composite scaffolds for cartilage repair.

Articular cartilage tissue engineering is being considered an alternative treatment strategy for promoting cartilage damage repair. Herein, we proposed a modular hydrogel-based bioink containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds integrating the micro and macro environment of the native articular cartilage. Gelatin methacryloyl (GelMA)/alginate microsphere was prepared by a microfluidic approach, and the chondrocytes embedded in the microspheres remained viable after being frozen and resuscitated. The modular hydrogel bioink could be printed via the gel-in-gel 3D bioprinting strategy for fabricating the multiscale hydrogel-based scaffolds. Meanwhile, the cells cultured in the scaffolds showed good proliferation and differentiation. Furthermore, we also found that the composite hydrogel was biocompatible in vivo. These results indicated that the modular hydrogel-based bioinks containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds could provide a 3D multiscale environment for enhancing cartilage repairing, which would be encouraging considering the numerous alternative applications in articular cartilage tissue engineering.

MicroRNA-124-3p Attenuated Retinal Neovascularization in Oxygen-Induced Retinopathy Mice by Inhibiting the Dysfunction of Retinal Neuroglial Cells through STAT3 Pathway.

MicroRNA (miRNA) is a non-coding RNA that can regulate the expression of many target genes, and it is widely involved in various important physiological activities. MiR-124-3p was found to associate with the normal development of retinal vessels in our previous study, but the mechanism of its anti-angiogenic effect on pathological retinal neovascularization still needed to be explored. Therefore, this study aimed to investigate the effect and mechanism of miR-124-3p on retinal neovascularization in mice with oxygen-induced retinopathy (OIR). Here, we found that intravitreal injection of miR-124-3p agomir attenuated pathological retinal neovascularization in OIR mice. Moreover, miR-124-3p preserved the astrocytic template, inhibited reactive gliosis, and reduced the inflammatory response as well as necroptosis. Furthermore, miR-124-3p inhibited the signal transducer and activator of transcription 3 (STAT3) pathway and decreased the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. Taken together, our results revealed that miR-124-3p inhibited retinal neovascularization and neuroglial dysfunction by targeting STAT3 in OIR mice.

Downregulation of miR-124-3p suppresses the development of the deep retinal blood vessels by enhancing the Stat1/Ripk1 pathway in mouse retinal microglia.

The study aimed to investigate the role of microRNA (miR)-124-3p in retinal angiogenesis in a mouse model. An intravitreal injection of miR-124-3p antagomir was used to knockdown the expression of miR-124-3p in the mouse retina at postnatal day (P)3. Immunofluorescent staining of both retinal frozen sections and whole retina were used to observe retinal vascular development in the P6, P9 and P12 mice, as well as the changes in retinal ganglion cells, astrocytes, Müller cells and microglia. Whole retinal RNA extracted from P9 mice was used for transcriptome sequencing. Following gene set enrichment analysis, the enriched genes caused by miR-124-3p inhibition were analyzed by immunofluorescent staining and western blot. Results indicated that deep vascular development was significantly inhibited by the activation of M1 phenotype microglia. Moreover, there were no notable effects on superficial retinal vascular development, the retinal ganglion cells, astrocytes, and Müller cells. The expression of the Stat1/Irf9/Eif2ak2/Ripk1 axis in the miR-124-3p knockdown group was significantly increased. The microglia penetrated deep into the retina and the activation of Ripk1(+) microglia significantly increased, which was accompanied by an increased level of apoptosis to inhibit the deep vascular sprout. Downregulation of miR-124-3p during the early retinal development can suppress the development of the deep retinal blood vessels by enhancing the expression level of the Stat1/Irf9/Eif2ak2/Ripk1 axis and inducing the cell apoptosis of the activation of Ripk1(+) microglia.

Downregulation of miR-210-3p Attenuates High Glucose-Induced Angiogenesis of Vascular Endothelial Cells via Targeting FGFRL1.

INTRODUCTION: Vascular endothelial cell injury and angiogenesis induced by hyperglycemia are the main pathological basis of vascular complications in diabetes mellitus. Our study aimed to investigate the role and mechanism of miR-210-3p in high glucose (HG)-induced angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with HG to mimic the pathological process of hyperglycemia. HUVECs were divided into the control group, HG group, HG+inhibitor-NC group, and HG+miR-210-3p inhibitor group. Proliferation and migration were tested by wound healing assay, tube formation, and Transwell assay. Quantitation real-time PCR and Western blots were performed to determine the expression of miR-210-3p and relative proteins, respectively. RESULTS: The level of miR-210-3p significantly increased in HUVECs treated by HG. The knockdown of miR-210-3p attenuated the tube formation, proliferation, and migration of cultured HUVECs in vitro to inhibit angiogenesis by increasing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) and then attenuating the phosphorylation of signal transducer and activator of transcription 3 (STAT3), extracellular regulated protein kinases, and protein kinase B (Akt). CONCLUSION: Our study revealed that miR-210-3p might be a promising target for treating diabetic-associated vascular injury.

Performance of the AIDRScreening system in detecting diabetic retinopathy in the fundus photographs of Chinese patients: a prospective, multicenter, clinical study.

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population worldwide, and there is a large unmet need for DR screening in China. This observational, prospective, multicenter, gold standard-controlled study sought to evaluate the effectiveness and safety of the AIDRScreening system (v. 1.0), which is an artificial intelligence (AI)-enabled system that detects DR in the Chinese population based on fundus photographs. Methods: Participants with diabetes mellitus (DM) were recruited. Fundus photographs (field 1 and field 2) of 1 eye in each participant were graded by the AIDRScreening system (v. 1.0) to detect referable DR (RDR). The results were compared to those of the masked manual grading (gold standard) system by the Zhongshan Image Reading Center. The primary outcomes were the sensitivity and specificity of the AIDRScreening system in detecting RDR. The other outcomes evaluated included the system's diagnostic accuracy, positive predictive value, negative predictive value, diagnostic accuracy gain rate, and average diagnostic time gain rate. Results: Among the 1,001 enrolled participants with DM, 962 (96.1%) were included in the final analyses. The participants had a median age of 60.61 years (range: 20.18-85.78 years), and 48.2% were men. The manual grading system detected RDR in 399 (41.48%) participants. The AIDRScreening system had a sensitivity of 86.72% (95% CI: 83.39-90.05%) and a specificity of 96.09% (95% CI: 94.14-97.54%) in the detection of RDR, and a false-positive rate of 3.91%. The diagnostic accuracy gain rate of the AIDRScreening system was 16.57% higher than that of the investigator, while the average diagnostic time gain rate was -37.32% lower. Conclusions: The automated AIDRScreening system can detect RDR with high accuracy, but cannot detect maculopathy. The implementation of the AIDRScreening system may increase the efficiency of DR screening.

MicroRNA-92a-3p Regulates Retinal Angiogenesis by Targeting SGK3 in Vascular Endothelial Cells.

Purpose: The purpose of this study was to investigate the effects and mechanism of microRNA (miR)-92a-3p in retinal angiogenesis in vitro and in vivo. Methods: The expression of miR-92a-3p was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Agomir-92a-3p was intravitreally injected into the right eye on postnatal day 3 (P3), P5, and P8 in the mice, with the agomir-NC injected left eye as the control. At P7, P9, and P12, immunofluorescence was performed to examine the retinal superficial vascular plexus, deep vascular plexus, proliferation, and apoptosis in retinal vascular endothelial cells (ECs). Human retinal microvascular endothelial cells (HRMECs) were treated with mimic-NC and mimic-92a-3p, then the tube formation, cell migration, and wound healing assays were used to detect the effect of miR-92a-3p on retinal angiogenesis in vitro. Agomir-92a-3p was also intravitreally injected into the right eye of oxygen-induced retinopathy (OIR) mice at P12, with the agomir-NC injected left eye as the control, the neovascularization was observed by retinal flatmount staining with isolectin B4 at P17. Bioinformatics and high-throughput sequencing were performed to identify potential target genes of miR-92a-3p. RT-qPCR and Western blot were carried out to detect the expression of SGK3, p-GSK3ß, GSK3ß, Bcl-xL, and cleaved caspase-3 in the HRMECs and mouse retinas. Results: The overexpression of miR-92a-3p inhibited the development of retinal superficial vascular plexus and deep vascular plexus, decreased the expression of Ki67, and increased the expression of cleaved caspase-3 in isolectin B4-labeled retinal vascular ECs. In vitro, the overexpression of miR-92a-3p markedly suppressed the tube formation, cell migration, and wound healing of cultured ECs. Overexpression of miR-92a-3p inhibited both in vivo and in vitro physiological angiogenesis by downregulating the expression of SGK3, p-GSK3ß/GSK3ß, and Bcl-xL. In addition, agomir-92a-3p inhibited the pathological retinal neovascularization of OIR mice, by targeting SGK3, p-GSK3ß/GSK3ß, and Bcl-xL. Conclusions: The miR-92a-3p could affect retinal angiogenesis by targeting SGK3 pathway, suggesting that miR-92a-3p may be a potential anti-angiogenic factor for retinal vascular disease.

The Modified Longitudinal Capsulotomy by Outside-In Approach in Hip Arthroscopy for Femoroplasty and Acetabular Labrum Repair-A Cohort Study.

Hip arthroscopy is difficult to perform due to the limited arthroscopic view. To solve this problem, the capsulotomy is an important technique. However, the existing capsulotomy approaches were not perfect in the surgical practice. Thus, this study aimed to propose a modified longitudinal capsulotomy by outside-in approach and demonstrate its feasibility and efficacy in arthroscopic femoroplasty and acetabular labrum repair. A retrospective cohort study was performed and twenty-two postoperative patients who underwent hip arthroscopy in our hospital from January 2019 to December 2021 were involved in this study. The patients (14 females and 8 males) had a mean age of 38.26 ± 12.82 years old. All patients were diagnosed cam deformity and labrum tear in the operation and underwent arthroscopic femoroplasty and labrum repair by the modified longitudinal capsulotomy. The mean follow-up time was 10.4 months with a range of 6−12 months. There were no major complications, including infection, neurapraxias, hip instability or revision in any patients. The average mHHS were 74.4 ± 15.2, 78.2 ± 13.7 and 85.7 ± 14.5 in 3 months, 6 months and 12 months after surgery, respectively, which were all better than that before surgery (44.9 ± 8.6) (p < 0.05). The average VAS were 2.8 ± 1.2, 1.5 ± 0.6 and 1.2 ± 0.7 in 3 months, 6 months and 12 months after surgery, respectively, which were all lower than that before surgery (5.5 ± 2.0) (p < 0.05). The modified longitudinal capsulotomy by outside-in approach is proved to be a safe and feasible method for hip arthroscopy considering to the feasibility, efficacy and security. The arthroscopic femoroplasty and labrum repair can be performed conveniently by this approach and the patient reported outcomes after surgery were better that before surgery in short-term follow-up. This new method is promising and suggested to be widely used clinically.

Effect of secretory leucocyte protease inhibitor on early tendon-to-bone healing after anterior cruciate ligament reconstruction in a rat model.

AIMS: To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. METHODS: In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. RESULTS: SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. CONCLUSION: SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503-512.

A Multicenter Clinical Study of the Automated Fundus Screening Algorithm.

Purpose: To evaluate the effectiveness of automated fundus screening software in detecting eye diseases by comparing the reported results against those given by human experts. Results: There were 1585 subjects who completed the procedure and yielded qualified images. The prevalence of referable diabetic retinopathy (RDR), glaucoma suspect (GCS), and referable macular diseases (RMD) were 20.4%, 23.2%, and 49.0%, respectively. The overall sensitivity values for RDR, GCS, and RMD diagnosis are 0.948 (95% confidence interval [CI], 0.918-0.967), 0.891 (95% CI, 0.855-0.919), and 0.901 (95% CI-0.878, 0.920), respectively. The overall specificity values for RDR, GCS, and RMD diagnosis are 0.954 (95% CI, 0.915-0.965), 0.993 (95% CI-0.986, 0.996), and 0.955 (95% CI-0.939, 0.968), respectively. Methods: We prospectively enrolled 1743 subjects at seven hospitals throughout China. At each hospital, an operator records the subjects' information, takes fundus images, and submits the images to the Image Reading Center of Zhongshan Ophthalmic Center, Sun Yat-Sen University (IRC). The IRC grades the images according to the study protocol. Meanwhile, these images will also be automatically screened by the artificial intelligence algorithm. Then, the analysis results of automated screening algorithm are compared against the grading results of IRC. The end point goals are lower bounds of 95% CI of sensitivity values that are greater than 0.85 for all three target diseases, and lower bounds of 95% CI of specificity values that are greater than 0.90 for RDR and 0.85 for GCS and RMD. Conclusions: Automated fundus screening software demonstrated a high sensitivity and specificity in detecting RDR, GCS, and RMD from color fundus imaged captured using various cameras. Translational Relevance: These findings suggest that automated software can improve the screening effectiveness for eye diseases, especially in a primary care context, where experienced ophthalmologists are scarce.

An Interaction-Based Method for Refining Results From Gene Set Enrichment Analysis.

Purpose: To demonstrate an interaction-based method for the refinement of Gene Set Enrichment Analysis (GSEA) results. Method: Intravitreal injection of miR-124-3p antagomir was used to knockdown the expression of miR-124-3p in mouse retina at postnatal day 3 (P3). Whole retinal RNA was extracted for mRNA transcriptome sequencing at P9. After preprocessing the dataset, GSEA was performed, and the leading-edge subsets were obtained. The Apriori algorithm was used to identify the frequent genes or gene sets from the union of the leading-edge subsets. A new statistic d was introduced to evaluate the frequent genes or gene sets. Reverse transcription quantitative PCR (RT-qPCR) was performed to validate the expression trend of candidate genes after the knockdown of miR-124-3p. Results: A total of 115,140 assembled transcript sequences were obtained from the clean data. With GSEA, the NOD-like receptor signaling pathway, C-type-like lectin receptor signaling pathway, phagosome, necroptosis, JAK-STAT signaling pathway, Toll-like receptor signaling pathway, leukocyte transendothelial migration, chemokine signaling pathway, NF-kappa B signaling pathway and RIG-I-like signaling pathway were identified as the top 10 enriched pathways, and their leading-edge subsets were obtained. After being refined by the Apriori algorithm and sorted by the value of the modulus of d , Prkcd, Irf9, Stat3, Cxcl12, Stat1, Stat2, Isg15, Eif2ak2, Il6st, Pdgfra, Socs4 and Csf2ra had the significant number of interactions and the greatest value of d to downstream genes among all frequent transactions. Results of RT-qPCR validation for the expression of candidate genes after the knockdown of miR-124-3p showed a similar trend to the RNA-Seq results. Conclusion: This study indicated that using the Apriori algorithm and defining the statistic d was a novel way to refine the GSEA results. We hope to convey the intricacies from the computational results to the low-throughput experiments, and to plan experimental investigations specifically.

Proteomic Analysis of Retinal Conditioned Medium: The Effect on Early Differentiation of Embryonic Stem Cells into Retina.

Stem cell replacement therapy has emerged as one of the most promising treatment options for retinal degenerative diseases, which are the main causes of irreversible vision loss. Three-dimensional (3D) retinal organoid culture is a cutting-edge technology for differentiating embryonic stem cells into retinal cells by forming a laminated retinal structure. However, 3D culture systems have strict requirements with respect to the experimental environment and culture technologies. Our study aimed to investigate the effect of retinal conditioned medium (RCM) at different developmental stages on the early differentiation of embryonic stem cells into retina in a 3D culture system. In this study, we added RCM to the 3D culture system and found that it could promote the differentiation of mouse embryonic stem cells (mESCs) into neuroretina. We further explored the possible mechanisms of RCM that regulate differentiation through proteomic analysis. RCM at different time points disclosed different protein profiles. Proteins which improved energy metabolism of mESCs might help improve the viability of embryonic bodies. We then screened out Snap25, Cntn1, Negr1, Dpysl2, Dpysl3, and Crmp1 as candidate proteins that might play roles in the differentiation and neurogenesis processes of mESCs, hoping to provide a basis for optimizing a retinal differentiation protocol from embryonic stem cells.

The application of platelet-rich plasma in the treatment of knee osteoarthritis: A literature review.

BACKGROUND: Primary knee osteoarthritis remains a difficult-to-control degenerative disease. With the rise in average life expectancy and the incidence of obesity, osteoarthritis has brought an increasing economic and physical burden on people. This article summarizes the latest understanding of platelet-rich plasma in the treatment of knee osteoarthritis, and reviews the economic issues of PRP. METHODS: The literatures in Pubmed, Embase, Cochrane library, Web-science and other databases were searched, and literature inclusion and exclusion criteria were formulated. According to the Cochrane systematic reviewer's manual, the included literatures were grouped, and qualitative descriptions and quantitative meta-analysis were performed. Continuous statistical methods were used to compare the effects and adverse effects of PRP before and after treatment, as well as between PRP and other conservative treatments. RESULTS: A total of 12 randomized controlled trials were included in this study. A total of 959 KOA patients (1070 knees) were enrolled and followed for 3-12 months. PRP total knee scores were significantly better than baseline at 1, 2, 3, 6 and 12 months after treatment (1 month: SMD = 0.60, P < 0.01; 2 months: SMD = 0.98, P < 0.01; 3 months: SMD = 1.16, P < 0.01; 6 months: SMD = 1.49, P < 0.01; 12 months: SMD = 1.47, P < 0.01). In terms of adverse reactions, PRP did not increase the risk of adverse events compared with HA (OR = 0.96, P = 0.85). CONCLUSIONS: Compared with many other treatment methods, intra-articular injection of PRP has been proven to be safe and effective to improve the quality of life of patients with KOA.

Asporin regulated by miR-26b-5p mediates chondrocyte senescence and exacerbates osteoarthritis progression via TGF-ß1/Smad2 pathway.

OBJECTIVES: This study aimed to investigate the role and mechanism of asporin in modulating chondrocyte senescence in OA pathology. METHODS: Asporin and senescence-related hallmark expression were examined in human and experimental OA mouse cartilage samples. Twelve-week-old male C57 mice were administered with recombinant protein (rm-asporin)- or asporin-siRNA-expressing lentiviruses via intra-articular injection once a week after destabilization of the medial meniscus (DMM) surgery to induce OA. Cartilage damage was measured using the Osteoarthritis Research Society International score. Senescence-associated ß-galactosidase (SA-ß-Gal) staining, γH2AX, p21 and p16INK4a were analysed by immunofluorescence staining and western blot to assess the specific role of asporin in chondrocyte senescence. The TGF-ß1-Smad2 signalling pathway and miR-26b-5p were further evaluated to explore the mechanism of asporin in OA. RESULTS: Asporin was upregulated in articular chondrocytes of OA patients and DMM mice and accompanied by accumulation of senescent cells. Asporin overexpression exaggerated OA progression, whereas silencing asporin restored chondrocyte homeostasis and deferred chondrocyte senescence, leading to markedly attenuated DMM-induced OA. Cellular and molecular analyses showed that asporin can be inhibited by miR-26b-5p, which was significantly downregulated in OA cartilage, leading to exacerbation of experimental OA partially through inhibition of TGF-ß1-Smad2 signalling in chondrocytes. CONCLUSIONS: Our findings indicate that asporin plays an essential role in chondrocyte senescence and OA pathogenesis. Upregulated by miR-26b-5p, asporin inhibits the TGF-ß1-Smad2 pathway to accelerate chondrocyte senescence and exacerbate cartilage degeneration. Targeting the miR-26b-5p-asporin-Smad2 axis may serve as a practical therapeutic strategy to delay chondrocyte senescence and OA development.

Transcriptomics and Metabolomics Changes Triggered by Inflorescence Removal in Panax notoginseng (Burk.).

The root of Panax notoginseng (Burk.), in which saponins are the major active components, is a famous traditional Chinese medicine used to stop bleeding and to decrease inflammation and heart disease. Inflorescence removal increases the yield and quality of P. notoginseng, but the underlying molecular mechanisms are unknown. Here, the differences between inflorescence-removal treatment and control groups of P. notoginseng were compared using transcriptomics and metabolomics analyses. Illumina sequencing of cDNA libraries prepared from the rhizomes, leaves and roots of the two groups independently identified 6,464, 4,584, and 7,220 differentially expressed genes (DEG), respectively. In total, 345 differentially expressed transcription factors (TFs), including MYB and WRKY family members, were induced by the inflorescence-removal treatment. Additionally, 215 DEGs involved in saponin terpenoid backbone biosynthetic pathways were identified. Most genes involved in the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways were activated by inflorescence removal. The co-expression analysis showed that the low expression levels of flavonoid biosynthesis-related genes (e.g., C4H and F3H) decreased the biosynthesis and accumulation of some flavonoids after inflorescence removal. The results not only provide new insights into the fundamental mechanisms underlying the poorly studied inflorescence-removal process in P. notoginseng and other rhizome crops, but they also represent an important resource for future research on gene functions during inflorescence-removal treatments and the reproductive stage.

Segmentation of Laser Marks of Diabetic Retinopathy in the Fundus Photographs Using Lightweight U-Net.

Diabetic retinopathy (DR) is a prevalent vision-threatening disease worldwide. Laser marks are the scars left after panretinal photocoagulation, a treatment to prevent patients with severe DR from losing vision. In this study, we develop a deep learning algorithm based on the lightweight U-Net to segment laser marks from the color fundus photos, which could help indicate a stage or providing valuable auxiliary information for the care of DR patients. We prepared our training and testing data, manually annotated by trained and experienced graders from Image Reading Center, Zhongshan Ophthalmic Center, publicly available to fill the vacancy of public image datasets dedicated to the segmentation of laser marks. The lightweight U-Net, along with two postprocessing procedures, achieved an AUC of 0.9824, an optimal sensitivity of 94.16%, and an optimal specificity of 92.82% on the segmentation of laser marks in fundus photographs. With accurate segmentation and high numeric metrics, the lightweight U-Net method showed its reliable performance in automatically segmenting laser marks in fundus photographs, which could help the AI assist the diagnosis of DR in the severe stage.

An Improved Device Clears Blockages in the Tube of Irrigation and Drainage Systems.

The outflow tube may be blocked during continuous irrigation for the treatment of septic joints. Although multiple solutions have been applied to clear the blockage, there are still many disadvantages. The success rate is difficult to guarantee, and bacteria may enter the joint cavity and cause secondary infection. We designed an improved irrigation and drainage system that avoids these disadvantages and is particularly convenient to use. In addition, the improved system provides more thorough lavage and drainage and prevents joint adhesion.

Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways.

BACKGROUND: To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development. METHODS: Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1ß and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages. RESULTS: Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1ß and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling. CONCLUSIONS: This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway.

Milk fat globule-epidermal growth factor (EGF) factor 8 (MFG-E8), as a necessary bridging molecule between apoptotic cells and phagocytic cells, has been widely studied in various organs and diseases, while the effect of MFG-E8 in osteoarthritis (OA) remains unclear. Here, we identified MFG-E8 as a key factor mediating chondrocyte senescence and macrophage polarization and revealed its role in the pathology of OA. We found that MFG-E8 expression was downregulated both locally and systemically as OA advanced in patients with OA and in mice after destabilization of the medial meniscus surgery (DMM) to induce OA. MFG-E8 loss caused striking progressive articular cartilage damage, synovial hyperplasia, and massive osteophyte formation in OA mice, which was relieved by intra-articular administration of recombinant mouse MFG-E8 (rmMFG-E8). Moreover, MFG-E8 restored chondrocyte homeostasis, deferred chondrocyte senescence and reprogrammed macrophages to the M2 subtype to alleviate OA. Further studies showed that MFG-E8 was inhibited by miR-99b-5p, expression of which was significantly upregulated in OA cartilage, leading to exacerbation of experimental OA partially through activation of NF-κB signaling in chondrocytes. Our findings established an essential role of MFG-E8 in chondrocyte senescence and macrophage reprogramming during OA, and identified intra-articular injection of MFG-E8 as a potential therapeutic target for OA prevention and treatment.

Clinical application of polyurethane meniscal scaffold: A meta-analysis.

OBJECTIVE: In patients with partial meniscus defect, the implantation of polyurethane meniscal scaffold has become a common method for the treatment of meniscus vascular entry and tissue regeneration. However, it is unclear whether polyurethane meniscal scaffold will yield better clinical and MRI results after surgery. This meta-analysis compared the clinical and MRI results of polyurethane meniscal scaffold in some patients with meniscus defects. METHODS: By searching PubMed, Embase, and Cochrane Library, a systematic review of studies evaluating the clinical outcomes of patients with polyurethane meniscal scaffold implantation. The search terms used are: "meniscus", "meniscal", "scaffold", "Actifit" "polyurethane" and "implant". The study was evaluated based on the patient's reported outcome score, accompanying surgery, and radiology results. Genovese scale was used to evaluate morphology and signal intensity, and Yulish score was used to evaluate the imaging performance of articular cartilage. RESULTS: There were 16 studies that met the inclusion criteria, a total of 613 patients, and the overall average follow-up time was 41 months. The clinical scores at the final follow-up, such as VAS, IKDC, Tegner, and KOOS, were significantly improved compared with preoperatively. The MS, SI, and IIRMC scores evaluated in MRI showed no significant difference between preoperative and final follow-up. However, for AC (OR 0.34, 95% CI 0.11-1.00; P = 0.05) and AME (OR 0.08, 95% CI 0.03-0.22; P < 0.01), the final follow-up results were worse than preoperatively. CONCLUSIONS: This meta-analysis found that compared with preoperative, the clinical effect of the final follow-up was significantly improved. However, MS, SI, and IIRMC in MRI parameters did not change significantly. In addition, the final follow-up results of AC and AME showed a deteriorating trend. Therefore, for patients with partial meniscus defects, polyurethane meniscal scaffold seem to be a viable option, and further research is needed to determine whether the deterioration of AC and AME is clinically relevant.