BACKGROUND:Recent studies have revealed heterogeneity among ribosomes. Pathological cardiac hypertrophy is characterized by profound alterations in translation. However, how ribosome heterogeneity contributes to this process remains largely unclear. METHODS:We used translating ribosome affinity purification coupled with mass spectrometry to profile ribosome-interacting proteins. Cardiomyocyte-specific gene manipulation was achieved through either genetic knockout or adeno-associated virus-mediated overexpression. Pathological cardiac hypertrophy was induced by transverse aortic constriction surgery in vivo and by phenylephrine stimulation in vitro. RESULTS:The cardiomyocyte-specific ribosome proteomics indicated dynamic alterations in ribosome-interacting proteins during pathological hypertrophy. Notably, multiple proteins associated with ribosome stalling were detected in the ribosome-interactome of hypertrophic hearts. Among these, we verified that CDK5RAP3 (CDK5 regulatory subunit-associated protein 3) exhibited the most specific ribosome binding in hypertrophic hearts. CDK5RAP3 was upregulated and recruited to ribosomes during pathological hypertrophy. It promoted RPL26 (ribosomal protein L26) UFMylation and ribosome-associated quality control on the mitochondrial surface. In vitro, CDK5RAP3 knockdown exacerbated cardiomyocyte hypertrophy induced by phenylephrine, whereas its overexpression attenuated it. In vivo, cardiomyocyte-specific CDK5RAP3 knockout promoted, while adeno-associated virus-mediated overexpression suppressed pathological cardiac hypertrophy induced by transverse aortic constriction. Mechanistically, ribosome stalling on the mitochondrial surface was exacerbated in hypertrophic hearts of both humans and mice, which was associated with impaired mitochondrial protein import. CDK5RAP3 enhanced ribosome-associated quality control, alleviated ribosome stalling, and restored mitochondrial protein import, thereby improving mitochondrial function. Notably, mitochondrial import of PDP1 was maintained by CDK5RAP3-mediated ribosome-associated quality control. Knockdown of PDK (pyruvate dehydrogenase kinase) 1/2, functional antagonists of PDP1, reversed cardiomyocyte hypertrophy caused by CDK5RAP3 deficiency. CONCLUSIONS:This study identifies CDK5RAP3-mediated ribosome-associated quality control on the mitochondrial surface as a critical protective mechanism that preserves protein import and mitochondrial function during pathological cardiac hypertrophy.

Small extracellular vesicles (sEVs) are naturally secreted nanovesicles that mediate intercellular communication by transporting biomolecules such as proteins and nucleic acids. Their inherent biocompatibility makes them promising platforms for RNA therapeutics; however, efficient encapsulation of small RNAs remains challenging. To address this, we developed the Protein N-Myristoylation-induced sEVs Loading (PMEVL) system. PMEVL employs a genetic construct encoding an N-Myristoylation peptide and, optionally, a small-RNA expression cassette in its 3'-untranslated region, enabling N-myristoylation-dependent, efficient, and specific RNA loading into sEVs. Mechanistically, PMEVL enhances sEVs biogenesis by activating ERK1/2 and inhibiting AMPK, while promoting RNA loading through recruitment of ANXA2 and key ESCRT components ALIX and TSG101. This system achieved highly efficient encapsulation of diverse functional RNAs, including exogenous/endogenous small RNAs (miRNAs, siRNAs) and messenger RNAs (e.g., GFP, mCherry), as well as co-loading of multiple siRNAs with proteins of interest. To demonstrate therapeutic potential, PMEVL-mediated delivery of Pcsk9 siRNA suppressed hepatic Pcsk9 expression in vitro and in vivo. In C57BL/6 mice, this treatment restored hepatic low-density lipoprotein receptor (LDLR) expression and significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol, without systemic toxicity. Furthermore, systematic screening of 181 peptides representing the N-terminal 15-18 residues of human N-myristoylated proteins identified candidates that substantially enhanced PMEVL loading efficiency. Collectively, PMEVL represents a versatile, efficient, and modular platform for loading RNA therapeutics into sEVs, with demonstrated co-loading capability for proteins in vitro.

Cardiac fibroblast (CF) differentiation into myofibroblasts is a crucial driver of cardiac fibrosis, leading to myocardial stiffness and eventually impairing heart function. Cardiomyocyte-fibroblast intercellular communication has emerged as a key regulatory way for CF activation and the fibrotic response. However, the molecular mechanisms linking cardiomyocyte secretomes to CF activation within heart failure remain poorly understood. Here, we identified a stress-responsive protein Maf1 in cardiomyocytes as a central regulator of CF activation in both in vivo and in vitro models of cardiac fibrosis. Maf1 overexpression (cardiomyocyte-specific Maf1 overexpression mice, Maf1 cOE) attenuated CF proliferation, ECM protein expression, and myofibroblast differentiation, while Maf1 loss-of-function (Maf1 knockout mice, Maf1-KO) exacerbated cardiac fibrosis. Notably, Maf1 directly suppresses the expression and secretion of Sfrp2 by affecting its promoter DNA methylation through DNA methyltransferase 1 (Dnmt1), which is essential for promoting CF activation and fibrosis. Sfrp2 overexpression or Sfrp2 recombinant protein treatment exacerbates TGFβ1-induced fibrosis, while silencing Dnmt1 reverses the upregulation of Sfrp2 by Maf1. These findings identify Maf1 as a pivotal link between cardiomyocyte secretomes and fibrosis, suggesting it as a potential therapeutic target to mitigate fibrosis and enhance cardiac recovery during heart failure.

Voltage-gated calcium channels are emerging regulators of cellular homeostasis, but their molecular interplay with mitochondrial bioenergetics in chondrocytes remains poorly characterized. This study elucidates how the T-type calcium channel CaV3.3 governs mitochondrial calcium-redox coupling through structural interactions with MICU1, the regulatory subunit of the mitochondrial calcium uniporter (MCU) complex. The absence of the CaV3.3 precipitated mitochondrial ultrastructural disorganization characterized, coupled with MICU1 downregulation and consequent loss of MCU gating fidelity. Through integrated transcriptomic-proteomic profiling and live-cell imaging, we demonstrate that CaV3.3 deficiency induces pathological mitochondrial calcium influx, triggering Reactive oxygen species (ROS) overproduction and bioenergetic collapse, these metabolic derangements activated intrinsic apoptosis. Notably, lentiviral overexpression of MICU1 in CaV3.3 knockout cells restored the mitochondrial calcium set point and inhibited ROS burst, while rescued cell proliferation and inhibited apoptosis execution. Our findings establish CaV3.3 as a redox rheostat coordinating MICU1-mediated mitochondrial calcium buffering, with direct implications for cartilage matrix maintenance and osteoarthritis therapy targeting calcium-handling macromolecules.

The lack of standardized Platelet-Rich Plasma (PRP) protocols for Knee Osteoarthritis (KOA), combined with significant patient variability, leads to inconsistent PRP effectiveness across studies. This study aims to assess the influence of PRP injection frequencies on KOA treatment and explore the role of patient characteristics and PRP properties in the treatment’s effectiveness. A retrospective cohort study was conducted with KOA patients who received three PRP injections (4-week intervals) at a hospital in Chongqing. The Wilcoxon signed-rank test was used to analyze differences in self-reported recovery rates across different treatment time points, with Bonferroni correction applied for significance level adjustment (α). The Mann-Whitney U test, Kruskal–Wallis H test, Spearman correlation analysis, and restricted cubic spline models were used to assess the associations between sex, baseline Kellgren–Lawrence grade, age, PRP red blood cell (RBC) concentration, PRP white blood cell (WBC) concentration, PRP platelet concentration, the multiple of PRP platelet concentration relative to the baseline autologous level (Enrichment-PLT), and self-reported recovery rates. The study included 28 KOA patients. Significant improvement in self-reported recovery rate was observed 4 weeks after the first treatment (median: 30.0

Inflammation is a critical pathological process in myocardial infarction. Although immunosuppressive therapies can mitigate inflammatory responses and improve outcomes in myocardial infarction, they also increase the risk of infections. Identifying novel regulators of local cardiac inflammation could provide safer therapeutic targets for myocardial ischemia/reperfusion injury. In this study, we identified a previously uncharacterized micropeptide, which we named Inflammation Associated MicroPeptide (IAMP). IAMP is predominantly expressed in cardiac fibroblasts, and its expression is closely associated with cardiac inflammation. Downregulation of IAMP promotes, whereas its overexpression prevents, the transformation of cardiac fibroblasts into a more inflammatory phenotype under stressed/stimulated conditions, as evidenced by changes in the expression and secretion of proinflammatory cytokines. Consequently, loss of IAMP function leads to uncontrolled inflammation and worsens cardiac injury following ischemia/reperfusion surgery. Mechanistically, IAMP promotes the degradation of HIF-1α by interacting with its stabilizing partner HSP90 and, thus, suppresses the transcription of proinflammatory genes downstream of HIF-1α. This study underscores the significance of fibroblast-mediated inflammation in cardiac ischemia/reperfusion injury and highlights the therapeutic potential of targeting micropeptides for myocardial infarction.

Osteoarthritis (OA) is a complex and heterogeneous degenerative joint disease, which demands a shift from generalized palliative care to precision medicine, necessitating accurate staging and grading for effective treatment, particularly in regenerative therapies. This paper comprehensively reviews the evolution and integration of OA classification systems, highlighting advancements toward greater sensitivity and objectivity. Understanding multifaceted pathogenesis is also crucial for developing targeted interventions. The authors detail precision regenerative strategies across physical therapy, traditional Chinese medicine (TCM) synergistic treatments, and advanced biological therapies. These approaches aim to modulate the joint microenvironment, promote cartilage regeneration, and inhibit degradation. Furthermore, the importance of temporal management through staged rehabilitation, including early functional training and load control, is emphasized for optimizing recovery. Long-term management requires a systematic approach involving regular disease progression monitoring, incorporating clinical, imaging, and molecular markers, alongside comprehensive lifestyle interventions focusing on weight management, physical activity, and other health pillars. The integration of precise diagnostics, stage-specific regenerative treatments, personalized rehabilitation, and holistic health management represents the future of OA care towards personalized and effective therapeutic outcomes.

The therapeutic efficacy of intra-articular mesenchymal stem cells (MSCs) injection for patients with osteoarthritis (OA) currently exhibits inconsistency, and the underlying mechanism remains elusive. It has been postulated that the immunomodulatory properties and paracrine activity of MSCs might be influenced by the inflammatory micro-environment within osteoarthritic joints, potentially contributing to this observed inconsistency. Adipose-derived MSCs (ADSCs) were isolated from SD rats and pre-treated with Toll-like receptor 3 (TLR3) agonist Poly I:C or Toll-like receptor 4 (TLR4) agonist LPS. The pre-treated ADSCs were then co-cultured with IL-1β-induced osteoarthritic chondrocytes using a Transwell system to analyze the paracrine effect of ADSCs on reversing the osteoarthritic phenotype of chondrocytes. RT-PCR and Western blot analysis revealed that Poly I:C and LPS pre-treatments up-regulated the expression of IL-10 and IL-6 in ADSCs, respectively. Furthermore, only Poly I:C-preconditioned ADSCs significantly promoted proliferation while inhibiting apoptosis in IL-1β-treated chondrocytes. Additionally, Poly I:C-preconditioned ADSCs downregulated MMP13 expression while upregulating aggrecan and collagen II expression levels in IL-1β-treated chondrocytes. TLR3 activation polarizes ADSCs into an immunomodulatory phenotype distinct from TLR4 activation, exerting differential effects on reversing the osteoarthritic phenotype of chondrocytes; thus indicating that MSCs’ paracrine effect regulated by TLRs signaling impacts the efficacy of intra-articular MSCs injection.

One of the features of pathological cardiac hypertrophy is enhanced translation and protein synthesis. Translational inhibition has been shown to be an effective means of treating cardiac hypertrophy, although system -wide side effects are common. Regulators of translation, such as cardiac -specific long noncoding RNAs (lncRNAs), could provide new, more targeted therapeutic approaches to inhibit cardiac hypertrophy. Therefore, we generated mice lacking a previously identified lncRNA named CARDINAL to examine its cardiac function. We demonstrate that CARDINAL is a cardiacspecific, ribosome -associated lncRNA and show that its expression was induced in the heart upon pathological cardiac hypertrophy and that its deletion in mice exacerbated stress -induced cardiac hypertrophy and augmented protein translation. In contrast, overexpression of CARDINAL attenuated cardiac hypertrophy in vivo and in vitro and suppressed hypertrophy -induced protein translation. Mechanistically, CARDINAL interacted with developmentally regulated GTPbinding protein 1 (DRG1) and blocked its interaction with DRG family regulatory protein 1 (DFRP1); as a result, DRG1 was downregulated, thereby modulating the rate of protein translation in the heart in response to stress. This study provides evidence for the therapeutic potential of targeting cardiac -specific lncRNAs to suppress disease -induced translational changes and to treat cardiac hypertrophy and heart failure.

One of the features of pathological cardiac hypertrophy is enhanced translation and protein synthesis. Translational inhibition has been shown to be an effective means of treating cardiac hypertrophy, although system-wide side effects are common. Regulators of translation, such as cardiac-specific long noncoding RNAs (lncRNAs), could provide new, more targeted therapeutic approaches to inhibit cardiac hypertrophy. Therefore, we generated mice lacking a previously identified lncRNA named CARDINAL to examine its cardiac function. We demonstrate that CARDINAL is a cardiac-specific, ribosome-associated lncRNA and show that its expression was induced in the heart upon pathological cardiac hypertrophy and that its deletion in mice exacerbated stress-induced cardiac hypertrophy and augmented protein translation. In contrast, overexpression of CARDINAL attenuated cardiac hypertrophy in vivo and in vitro and suppressed hypertrophy-induced protein translation. Mechanistically, CARDINAL interacted with developmentally regulated GTP-binding protein 1 (DRG1) and blocked its interaction with DRG family regulatory protein 1 (DFRP1); as a result, DRG1 was downregulated, thereby modulating the rate of protein translation in the heart in response to stress. This study provides evidence for the therapeutic potential of targeting cardiac-specific lncRNAs to suppress disease-induced translational changes and to treat cardiac hypertrophy and heart failure.

Diabetic chronic wounds are notoriously difficult to heal as a result of their susceptibility to infection. To address this issue, we constructed an innovated and adaptable solution in the form of injectable chitosan (CS) hydrogel, denoted as CCOD, with enhanced antibacterial and anti-inflammatory properties. This hydrogel is created through a Schiff base reaction that combines chitosan-grafted chlorogenic acid (CS-CGA) and oxidized hyaluronic acid (OHA) with deferoxamine (DFO) as a model drug. The combination of CS and CGA has demonstrated excellent antibacterial and anti-inflammatory properties, while grafting played a pivotal role in making these positive effects stable. These unique features make it possible to customize injectable hydrogel and fit any wound shape, allowing for more effective and personalized treatment of complex bacterial infections. Furthermore, the hydrogel system is not only effective against inflammation and bacterial infections but also possesses antioxidant and angiogenic abilities, making it an ideal solution for the repair of chronic wounds that have been previously thought of as unmanageable.

Recent studies highlight the vital role of oxidative stress and reactive oxygen species (ROS) during progression of osteoarthritis (OA). Attenuating oxidative stress and reducing reactive oxygen species generation in joints represent reasonable strategies for the treatment of osteoarthritis. To address the potential question for clinical translation, and improve the biocompatibility and long-term performance of current antioxidants, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity and first applied to osteoarthritis intervention. Our in vitro results showed that Ta-NH2 NPs were stable with good biocompatibility, and protected viability and hyaline-like phenotype in H2O2-challenged chondrocytes. In addition, the in vivo biodistribution data demonstrated a sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage without organ toxicity and abnormality in hemogram or blood biochemistry indexes. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced osteoarthritis model. This study preliminarily explored the potential of simply modified metal nanoparticles as effective reactive oxygen species scavenging agent for osteoarthritis intervention, and offered a novel strategy to achieve sustained reactive oxygen species suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.

AIMS:The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration.METHODS AND RESULTS:We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway.CONCLUSION:Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.

Enhancement of protein synthesis from mRNA translation is one of the key steps supporting cardiomyocyte hypertrophy during cardiac remodeling. The methyltransferase-like5 (METTL5), which catalyzes m6A modification of 18S rRNA at position A1832, has been shown to regulate the efficiency of mRNA translation during the differentiation of ES cells and the growth of cancer cells. It remains unknown whether and how METTL5 regulates cardiac hypertrophy. In this study, we have generated a mouse model, METTL5-cKO, with cardiac-specific depletion of METTL5 in vivo. Loss function of METTL5 promotes pressure overload-induced cardiomyocyte hypertrophy and adverse remodeling. The regulatory function of METTL5 in hypertrophic growth of cardiomyocytes was further confirmed with both gain- and loss-of-function approaches in primary cardiomyocytes. Mechanically, METTL5 can modulate the mRNA translation of SUZ12, a core component of PRC2 complex, and further regulate the transcriptomic shift during cardiac hypertrophy. Altogether, our study may uncover an important translational regulator of cardiac hypertrophy through m6A modification.

Background: N6-methyladenosine (m6A) plays a critical role in various biological processes. However, no study has addressed the role of m6A modification in the statin-induced protection of endothelial cells (ECs). Methods: Quantitative real-time polymerase chain reaction and Western blotting analyses were used to study the expression of m6A regulatory genes in atorvastatin-treated ECs. Gain- and loss-of-function assays, methylated RNA immunoprecipitation analysis, and dual-luciferase reporter assays were performed to clarify the function of FTO (fat mass and obesity-associated protein) in ECs. Results: Atorvastatin decreased FTO protein expression in ECs. The knockdown of FTO enhanced the mRNA and protein expression of KLF2 (Kruppel-like factor 2) and eNOS (endothelial NO synthase) but attenuated TNFα (tumor necrosis factor alpha)-induced VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) expression, as well as the adhesion of monocytes to ECs. Conversely, FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. Subsequent investigations demonstrated that KLF2 and eNOS are functionally critical targets of FTO. Mechanistically, FTO interacted with KLF2 and eNOS transcripts and regulated their expression in an m6A-dependent manner. After FTO silencing, KLF2 and eNOS transcripts with higher levels of m6A modification in their 3′ untranslated regions were captured by YTHDF3 (YT521-B homology m6A RNA-binding protein 3), resulting in mRNA stabilization and the induction of KLF2 and eNOS protein expression. Conclusions: FTO might serve as a novel molecular target to modulate endothelial function in vascular diseases.

Pathological cardiac hypertrophy is an independent risk factor for the development of heart failure. Long noncoding RNAs (lncRNAs), an emerging class of non-protein-coding transcripts, are involved in regulation of multiple cardiac diseases through diverse molecular mechanism, whereas the role of cytoplasmic lncRNAs in regulating cardiac hypertrophy remains unclear. In this study, we identified a novel and functional long noncoding RNA Gm17501, which was predominantly expressed in the cytoplasm of cardiomyocytes. The expression level of lncRNA Gm17501 was altered in cardiac hypertrophy induced by pressure overload and phenylephrine treatment. Moreover, lncRNA Gm17501 expression was decreased in the heart tissue of patients with heart failure. Silencing lncRNA Gm17501 aggravated cardiac hypertrophy under pathological stress. Inhibition of lncRNA Gm17501 did not alter the expression of nearby genes but decreased mRNA level of calcium handling proteins which were involved in cardiac contraction. Therefore, the cytoplasmic lncRNA Gm17501 might protect cardiomyocytes against hypertrophy, possibly by maintaining calcium signaling pathway.

Abstract Background Osteoarthritis (OA), which involves the dysfunction of articular cartilage, is the most common form of joint disease that results in arthralgia, joint deformation and limited mobility in patients. Recent studies highlighted the vital role of oxidative stress and reactive oxygen species (ROS) during progression of OA. Therefore, attenuating oxidative stress and reducing ROS generation in articular joints represent reasonable strategies for the treatment of OA. However, in addition to instability of current antioxidants caused by fluctuation in osteoarthritic physicochemical microenvironment, poor biocompatibility and short articular joint retention also seriously hindered their clinical application. Results Considering the above-mentioned, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity. Our in vitro results showed that Ta-NH2 NPs had good biocompatibility and stability, and could protect viability and hyaline-like phenotype in chondrocyte under H2O2 challenge. In addition, the in vivo biodistribution data demonstrated sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage with unnoticed organ toxicity and abnormity in hemogram and blood biochemistry analyses. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced OA model. Conclusion This study explored the potential of Ta-NH2 NPs as effective ROS scavenging agent for intra-articular injection, and offered a novel strategy to achieve sustained ROS suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.

目的 建立HPLC-DAD法同时测定益肾健骨丸(当归、枸杞子、苏木等)中5种成分的含量.方法 该药物甲醇提取液的分析采用Waters Symmetry C18色谱柱(250 mmx4.6 mm,5 μm);流动相甲醇-0.2％磷酸,梯度洗脱;体积流量1 mL/min;检测波长230、330 nm;柱温25℃.结果 龙胆苦苷、马钱苷、芍药苷、阿魏酸、毛蕊花糖苷分别在63.60～636.00 μg/mL(r=0.999 9)、5.90～59.00 μ,g/mL(r=0.999 6)、40.125～401.25 μg/mL(r=0.999 7)、2.062 5～20.625 μ.g/mL(r=0.999 9)、5.775～57.75 μg/mL(r= 0.999 8)范围内线性关系良好,平均加样回收率分别为100.5％、99.6％、100.4％、100.1％、99.57％,RSD 分别为1.05％、1.36％、1.19％、1.55％、1.24％.结论 该方法简便可靠,重复性好,可用于益肾健骨丸的质量控制.

Objective: Many tissues contained resident mesenchymal stromal/stem cells (MSCs) that facilitated tissue hemostasis and repair. However, there is no typical marker to identify the resident cardiac MSCs. We aimed to determine if CD51 could be an optimal marker of cardiac MSCs and assess their therapeutic potential for mice with acute myocardial infarction (AMI).Methods: Cardiac-derived CD51+CD31–CD45–Ter119– cells (named CD51+cMSCs) were isolated from C57BL/6 mice(7-day-old) by flow cytometry. The CD51+cMSCs were characterized by proliferation capacity, multi-differentiation potential, and expression of typical MSC-related markers. Adult C57BL/6 mice (12-week-old) were utilized for an AMI model via permanently ligating the left anterior descending coronary artery. The therapeutic efficacy of CD51+cMSCs was estimated by echocardiography and pathological staining. To determine the underlying mechanism, lentiviruses were utilized to knock down gene (stem cell factor [SCF]) expression of CD51+cMSCs.Results: In this study, CD51 was expressed in the entire layers of the cardiac wall in mice, including endocardium, epicardium, and myocardium, and its expression was decreased with age. Importantly, the CD51+cMSCs possessed potent self-renewal potential and multi-lineage differentiation capacity in vitro and also expressed typical MSC-related surface proteins. Furthermore, CD51+cMSC transplantation significantly improved cardiac function and attenuated cardiac fibrosis through pro-angiogenesis activity after myocardial infarction in mice. Moreover, SCF secreted by CD51+cMSCs played an important role in angiogenesis both in vivo and in vitro.Conclusions: Collectively, CD51 is a novel marker of cardiac resident MSCs, and CD51+cMSC therapy enhances cardiac repair at least partly through SCF-mediated angiogenesis.

目的 探讨关节镜下"8"字缝线与克氏针内固定治疗儿童前交叉韧带(ACL)胫骨止点撕脱骨折的临床疗效.方法 48例ACL胫骨止点撕脱骨折患儿采用关节镜下"8"字缝线("8"字缝线组,26例)与克氏针内固定(克氏针组,22例)治疗.末次随访时记录膝关节活动度、Lysholm评分和IKDC评分.结果 患儿均获得随访,时间12～24个月.两组前抽屉试验及Lachman试验均转为阴性.末次随访时,两组膝关节活动度、Lysholm评分和IKDC评分均高于术前(P<0.05);两组间3项比较差异均无统计学意义(P>0.05).结论 关节镜下"8"字缝线与克氏针内固定治疗儿童ACL胫骨止点撕脱骨折疗效相当,而"8"字缝线内固定无骨骺损伤风险,术后无需取出.