Evaluation of biomechanical properties and biocompatibility: are partially absorbable cords eligible for anterior cruciate ligament reconstruction?

Introduction: Independent augmentation technology based on reinforcing devices has been reported to signifi-cantly reduce the elongation behavior of graft and improve knee stability after anterior cruciate ligament reconstruction (ACLR). Using biodegradable devices could reduce the risk of severe inflammatory reactions due to particle accumulation from foreign bodies. Given the limitations of the mechanical properties of biodegradable materials, partially biodegradable composite devices may offer a compromise strategy. Methods: Three types of partially absorbable core-sheath sutures, including low-absorbable cord (LA-C), medium-absorbable cord (MA-C) and high-absorbable cord (HA-C), were braided using unabsorbable ultra-high molecular weight polyethylene (UHMWPE) yarn and absorbable polydioxanone (PDO) monofil-ament bundle based on the desired configuration. The feasibility of these partially absorbable cords were verified by biomechanical testing, material degradation testing, and cell experiments, all performed in vitro. Results: Reinforcement of an 8 mm graft with the cords decreased dynamic elongation by 24%-76%, was positively related to dynamic stiffness, and increased the failure load by 44%-105%, during which LA-C showed maximum enhancement. Human ligament-derived fibroblasts showed good proliferation and vitality on each cord over 2 weeks and aligned themselves in the direction of the fibers, especially the UHMWPE portion. Discussion: This study supports the potential of partially degradable UHMWPE/PDO cords, particularly LA-C, for graft protection. Nervertheless, a higher proportion of biodegradable material results in lower stiffness, which may impair the protective and lead to mechanical instability during degradation.

A Multicentre Randomized Controlled Clinical Study of Cross Electro-Nape-Acupuncture (CENA) for the Treatment of Pseudobulbar Palsy in Patients with Tracheotomy Intubation for Severe Cerebral Haemorrhage.

Objective: The objective is to evaluate the clinical efficacy of cross electro-nape-acupuncture (CENA) in the treatment of pseudobulbar palsy in patients with tracheotomy intubation for severe cerebral haemorrhage and to provide an innovative acupuncture method for the treatment of such patients. Methods: A total of 126 patients from six trial centres who met the inclusion criteria were randomly divided into three groups according to the random number table method in the ratio of 1 : 1 : 1, with 42 patients in each group, and the three groups were divided into CENA group, electro-acupuncture group, and acupuncture group. Each group's acupuncture treatment lasted for 30 minutes, and the needles were removed at the end of the treatment. Acupuncture was performed once a week on Sunday only and twice a day from Monday to Saturday, a total of 4 weeks of treatment. The SWT, FDA, ChSWAL-QOL, and TCRGS scores of the three groups of patients before and after treatment were compared to evaluate the effect of CENA on remodelling the function of swallowing reflex and cough reflex and promoting the recovery of dysarthria and swallowing quality of life in pseudobulbar palsy in patients with tracheotomy intubation for severe cerebral haemorrhage. Results: After treatment, the WST and TCRGS grade scores decreased and the FDA and ChSWAL-QOL scores increased significantly in all three groups compared with the pretreatment scores and were statistically significant. There was a significant difference between the three groups for these four indicators after treatment; the comparison between groups showed significant differences in the CENA group compared to the electro-acupuncture and acupuncture groups. The efficiency of the CENA group was significantly better than that of the electro-acupuncture and acupuncture groups. Conclusion: Compared with the acupuncture and electro-acupuncture groups, the CENA could better promote the remodelling of swallowing function and cough reflex function, promote the recovery of dysarthria, and better improve the quality of life of patients with pseudobulbar palsy from tracheotomy intubation in severe cerebral haemorrhage.

MicroRNA-146a-5p alleviates the pathogenesis of osteoarthritis by inhibiting SDF-1/CXCR4-induced chondrocyte autophagy.

BACKGROUND: SDF-1/CXCR4 signaling promotes osteoarthritis (OA) development. CXCR4 is a potential target of miR-146a-5p. This study investigated the therapeutic role and the underlying mechanism of miR-146a-5p in OA. METHODS: Human primary chondrocytes C28/I2 were stimulated with SDF-1. Cell viability and LDH release were examined. Chondrocyte autophagy was assessed using Western blot analysis, ptfLC3 transfection, and transmission electron microscopy. MiR-146a-5p mimics were transfected into C28/I2 cells to investigate the role of miR-146a-5p in SDF-1/CXCR4-induced autophagy of chondrocytes. An SDF-1-induced rabbit OA model was established to investigate the therapeutic role of miR-146a-5p in OA. Histological staining was performed to observe the morphology of osteochondral tissue. RESULTS: SDF-1/CXCR4 signaling promoted autophagy in C28/I2 cells, as demonstrated by increased LC3-II protein expression and autophagic flux induced by SDF-1. SDF-1 treatment significantly inhibited cell proliferation while promoting necrosis and autophagosome formation in C28/I2 cells. In the presence of SDF-1, miR-146a-5p overexpression in C28/I2 cells suppressed CXCR4 mRNA expression, LC3-II and Beclin-1 protein expression, LDH release, and autophagic flux. In addition, SDF-1 increased the autophagy of chondrocytes in rabbits and promoted the development of OA. Compared with the negative control, miR-146a-5p significantly reduced the morphological abnormalities of the rabbit cartilage that were induced by SDF-1, as well as the number of LC3-II-positive cells, protein expression of LC3-II and Beclin 1, and mRNA expression of CXCR4 in osteochondral tissue. These effects were reversed by the autophagy agonist rapamycin. CONCLUSIONS: SDF-1/CXCR4 promotes OA development by enhancing chondrocyte autophagy. MicroRNA-146a-5p may alleviate OA by suppressing CXCR4 mRNA expression and SDF-1/CXCR4-induced chondrocyte autophagy.

Diagnostic nomogram to differentiate between epididymal tuberculosis and bacterial epididymitis.

PURPOSE: We developed and validated a diagnostic nomogram for differentiating epididymal tuberculosis (TB) from bacterial epididymitis. METHODS: In this retrospective study, we developed a prediction model based on demographics and clinical characteristics. Eligible patients were randomly divided into derivation and validation cohorts (ratio 7:3). Univariate and multivariate regression analyses were used to filter variables and select predictors. Multivariate logistic regression was used to construct the nomogram. Concordance index (C-index), calibration plots, and decision curves analysis (DCA) were used to assess the discrimination, calibration, and clinical usefulness of the nomogram. RESULTS: We included 147 patients (epididymal TB, 93; bacterial epididymitis, 54). The derivation cohort included 66 patients with epididymal TB and 38 with bacterial epididymitis; the validation cohort included 27 patients with epididymal TB and 16 with bacterial epididymitis. One regression model was built from three differential variables: body mass index, purified protein derivative, and chronic infection. Accordingly, one nomogram was developed. The model had good discrimination and calibration. C-indexes of the derivation and validation cohorts were 0.89 and 0.98 (95% confidence intervals, 0.83-0.95 and 0.94-1.01), respectively. DCA showed that the proposed nomogram was useful for differentiation. CONCLUSION: The nomogram can differentiate between epididymal TB and bacterial epididymitis.

Construction and Simulation of Biomechanical Model of Human Hip Joint Muscle-Tendon Assisted by Elastic External Tendon by Hill Muscle Model.

Based on the Hill muscle model (HMM), a biomechanical model of human hip muscle tendon assisted by elastic external tendon (EET) was preliminarily established to investigate and analyze the biomechanical transition between the hip joint (HJ) and related muscle tendons. Using the HMM, the optimal muscle fiber length and muscle force scaling variables were introduced by means of constrained optimization problems and were optimized. The optimized HMM was constructed with human parameters of 170 cm and 70 kg. The biomechanical model simulation test of the hip muscle tendon was performed in the automatic dynamic analysis of mechanical systems (ADAMS) software to analyze and optimize the changes in the root mean square error (RMSE), biological moment, muscle moment distribution coefficient (MDC), muscle moment, muscle force, muscle power, and mechanical work of the activation curves of the hip major muscle, iliopsoas muscle, rectus femoris muscle, and hamstring muscle under analyzing the optimized HMM and under different EET auxiliary stiffnesses from the joint moment level, joint level, and muscle level, respectively. It was found that the trends of the output joint moment of the optimized HMM and the biological moment of the human HJ were basically the same, r 2 = 0.883 and RMSE = 0.18 Nm/kg, and the average metabolizable energy consumption of the HJ was (243.77 ± 1.59) J. In the range of 35%∼65% of gait cycle (GC), the auxiliary moment showed a significant downward trend with the increase of EET stiffness, when the EET stiffness of the human body was less than 200 Nm/rad, the biological moment of the human HJ gradually decreased with the increase of EET stiffness, and the MDC of the iliopsoas and hamstring muscles gradually decreased; when the EET stiffness was greater than 200 Nm/rad, the increase of the total moment of the extensor muscles significantly increased, the MDC of the gluteus maximus and rectus muscles gradually increased, and the gluteus maximus and hamstring muscle moments and muscle forces gradually increased; the results show that the optimized muscle model based on Hill can reflect the law of human movement and complete the simulation test of HJ movements, which provides a new idea for the analysis of energy migration in the musculoskeletal system of the lower limb.

[Mid-term effectiveness analysis of combined knee extensor mechanism realignment with bone anchor for recurrent patella dislocation].

Objective: To explore the mid-term effectiveness of combined knee extensor mechanism realignment with bone anchor for recurrent patella dislocation. Methods: Between August 2017 and May 2019, 21 patients with recurrent patella dislocation underwent combined knee extensor mechanism realigament with bone anchor and followed up more than 3 years. There were 8 males and 13 females with an average age of 19.4 years (range, 13-26 years). All 21 patients had a history of recurrent patellar dislocation for 2-5 times (median, 3 times), and the disease duration was 1-16 years (mean, 5 years). The preoperative Lysholm score was 67.5±6.3 and the Kujula score was 64.1±7.0. The defect of meniscus, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments were excluded by MRI examination; CT examination showed that the tibial tuberosity-trochlear groove distance was 2.05-2.56 cm, with an average of 2.16 cm; X-ray examination showed that lower limb force line was abnormal. The effectiveness were evaluated by Lysholm score and Kujula score before operation and at 3 years after operation, and Insall evaluation standard at 3 years after operation. Results: All the incisions healed by first intention, and there was no surgical complication such as lower extremity deep vein thrombosis, incision infection, and nerve injury. All 21 patients were followed up 3.0-3.5 years, with an average of 3.2 years. Anteroposterior and lateral X-ray films of the knee joint at 3 years after operation showed that the position of the patella was normal, and the axial X-ray films of the patella (30°, 60°, 90°) showed that the patellofemoral joint had a good relationship. During the follow-up, there was no anchor drop or fracture, no obvious pseudarthrosis formation, and no epiphyseal injury in the minor patients. The Lysholm score was 91.5±7.1 and the Kujula score was 88.1±7.6 at 3 years after operation, which were significantly improved when compared with those before operation ( t=11.57, P=0.00; t=12.78, P=0.00). According to the Insall evaluation criteria, 12 cases were excellent, 4 cases were good, 4 cases were fair, and 1 case was poor, with an excellent and good rate of 76.2%. Conclusion: Combined knee extensor mechanism realignment with bone anchor is a simple and reliable way to treat the recurrent patella dislocation, with a satisfactory mid-term effectiveness and less complications; however, its long-term effectiveness needs further follow-up.

Clinical Efficacy of Auricular Acupressure plus Eye Exercises in the Treatment of Adolescent Pseudomyopia.

Objective: To assess the clinical efficacy of auricular acupressure plus eye exercises in the treatment of adolescent pseudomyopia, to discover an easier and safer way to treat pseudomyopia. Methods: Forty adolescent patients with pseudomyopia were randomly recruited and assigned (1 : 1) to receive either eye exercises (single group, including 11 males and 9 females) or auricular acupressure plus eye exercises (combined group, including 12 males and 8 females). The clinical endpoint was the clinical efficacy after 28 days of treatment. Results: The baseline characteristics of the combined group were comparable with those of the single group (P > 0.05). Auricular acupressure plus eye exercises was associated with a significantly higher clinical efficacy versus eye exercises alone (P < 0.05). Conclusion: Ear acupressure plus eye exercises features promising clinical efficacy in the treatment of adolescent pseudomyopia, effectively arresting the progression of pseudomyopia to true myopia.

[Three-dimensional finite element study on combined proximal and distal knee extension rearrangement for recurrent patellar dislocation].

Objective: To establish a three-dimensional finite element analysis model of the knee joint in fresh frozen cadavers, to verify the validity of the model and to simulate the stress distribution characteristics of the patellofemoral joint after combined proximal and distal knee extension rearrangement surgery for recurrent patellar dislocation. Methods: One male and one female fresh frozen cadavers (4 knees in total), using voluntary body donations, were used to measure the maximum pressure on the patellofemoral articular surface at each passive flexion angle (0°, 30°, 60°, 90°, 120°) of the normal knee joint and the model after combined proximal and distal knee extension rearrangement surgery for recurrent patellar dislocation with tibial tuberosity-trochlear groove distance (TT-TG) value >2.00 cm using pressure-sensitive paper, respectively. Then, the 2 freshly frozen cadavers were used to construct three-dimensional finite element models of normal knee joints and postoperative knee joints, and the maximum pressure on the patellofemoral articular surface was measured at various passive flexion angles. The maximum pressure was compared with the measurement results of the pressure-sensitive paper to verify the validity of the three-dimensional finite element model. In addition, the maximum pressure on the patellofemoral joint surface measured by three-dimensional finite element was compared between the normal knee joint and the postoperative knee joint at various passive flexion angles, so as to obtain an effective three-dimensional finite element model for the simulation study of the stress distribution characteristics of the patellofemoral joint after combined proximal and distal knee extension rearrangement surgery for recurrent patellar dislocation. Results: The maximum pressure on the patellofemoral joint surface measured by pressure-sensitive paper and three-dimensional finite element measurements were similar at all passive flexion angles in the normal knee joint, with a difference of -0.08-0.06 MPa; the maximum pressure on the patellofemoral joint surface measured by pressure-sensitive paper and three-dimensional finite element measurements were also similar at all passive flexion angles in the knee after combined proximal and distal knee extension rearrangement surgery, with a difference of -0.04-0.09 MPa. The maximum pressure on the patellofemoral joint surface measured by three-dimensional finite elements were also similar between the normal knee joint and the knee joint after combined proximal and distal knee extension rearrangement surgery at all passive flexion angles, with a difference of -0.50--0.03 MPa. Conclusion: The three-dimensional finite element model of the normal knee joint and the knee joint after combined proximal and distal knee extension rearrangement surgery can accurately and effectively quantify the change in the maximum pressure on the patellofemoral joint surface; for recurrent patellar dislocations with TT-TG value>2.00 cm, the combined proximal and distal knee extension rearrangement surgery can achieve a maximum pressure of the patellofemoral joint surface similar to that of the normal knee joint.

Effects of cross electro-nape-acupuncture (CENA) on recovery of consciousness and tracheotomy tube sealing in serious cerebral hemorrhage.

OBJECTIVE: This study was designed to explore the effects of cross electro-nape-acupuncture (CENA) treatment on the recovery of consciousness and tracheotomy tube sealing in patients with serious cerebral hemorrhage (SCH). METHODS: A total of 60 patients with SCH admitted to the Intensive Care Unit of the South Hospital of the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from November 2020 to June 2021 were selected and randomized into two groups: the CENA group and a control group, given no acupuncture. Both groups were given the same basic treatment and patients in the CENA group were additionally given CENA treatment. Glasgow coma scale (GCS) scores, mismatch negative wave (MMN) and the cough reflex grading score (TCRGS) were recorded and compared after treatment for four weeks. The time to tracheostomy tube sealing was also recorded. RESULTS: After treatment, the GCS scores and MMN latency values of the two groups were significantly improved, with significantly better GCS scores and MMN latency values in the CENA group than in the control group. After treatment, the two groups of TCRGS were reduced, with more significant decreases in the CENA group than in the control group. CONCLUSION: With CENA, it took less time to achieve recovery of consciousness, improve cough reflex score and shortened the time to tracheal tube cutting and sealing in patients with SCH.

Finite Element Analysis of Femoral-Acetabular Impingement (FAI) Based on Three-Dimensional Reconstruction.

In order to solve the problem that people often have pain in the hip joint, it is more meaningful to study femoral-acetabular impingement syndrome in the future. This article aims to study the finite element analysis of femoral-acetabular impingement based on three-dimensional reconstruction. This paper proposes a selective image matching strategy. In the feature matching stage, all images are not matched in pairs, but the corresponding camera distance between the images is calculated initially, which has little effect on the number of features and greatly reduces the time of feature matching, thereby reducing the time cost of 3D reconstruction. In this experiment, a double-blind experiment was used to check the range of motion of all hip joints. Two senior radiologists read the obtained hip joint orthographic films to screen out the hip joint orthographic films that meet the requirements. Experimental data shows that although the initial matching points of the algorithm in this paper are lower than those of the traditional algorithm, the final number of matching points is higher than that of the traditional algorithm. When the final number of patches is fixed to 10000, the initial patch required by the algorithm in this paper is more than that required by the SAD algorithm, nearly 13%, but the total storage requirement is 56.4% of the SAD algorithm, which is a big improvement.

Effects of the triple therapy of carnosine glycoside, edaravone, and Xueshuantong in hemorrhagic cerebral infarction.

OBJECTIVE: This study was designed to evaluate the effects of the triple therapy of Muscular Amino Acid and Peptides and Nucleosides (MAAPN), edaravone, and Xueshuantong on neurological function, tumor volume, and adverse reactions in patients with hemorrhagic cerebral infarction. METHODS: In this retrospective study, a total of 115 patients with hemorrhagic cerebral infarction admitted to the hospital from January 2020 to January 2021 were enrolled and assigned to the observation group (n=57) or the control group (n=58) according to different treatment methods. The two groups were both treated with a conventional treatment regimen, and the observation group was additionally given carnosine, edaravone, and Xueshuantong, with a course of treatment spanning 14 days. The neurological and motor functions and changes in cerebral edema and cerebral infarct lesion size in patients were evaluated. The levels of inflammatory factors, blood lipids, neuron-specific enolase (NSE), S-100ß, and matrix metalloproteinase-9 (MMP-9) of the two groups were determined and compared. The adverse effects and rebleeding of patients were recorded. The Barthel index (BI) was used to evaluate the quality of life of patients. RESULTS: The treatment efficiency in the observation group was significantly higher than that in the control group (P<0.05). After treatment, the observation group obtained more favorable outcomes in terms of the neurological and motor functions, lesions of brain edema and cerebral infarction, and BI scores, than those of the control group (all P<0.05). In addition, after treatment, the levels of inflammatory factors, blood lipids, NSE, S-100ß, MMP-9, plasma viscosity, and whole blood viscosity of the two groups of patients all decreased remarkably, with better outcomes in the observation group when compared with the control group (all P<0.05). The observation group showed a markedly lower rebleeding rate than the control group (P<0.05). CONCLUSION: For patients with hemorrhagic cerebral infarction, the triple therapy of carnosine glycoside, edaravone, and Xueshuantong effectively enhances the neurological and motor function, reduces cerebral edema and cerebral infarction, and improves the quality of life, with high safety.

Effects of Tissue-engineered Bone by Coculture of Adipose-derived Stem Cells and Vascular Endothelial Cells on Host Immune Status.

AIM: The study aimed to explore the effects of tissue-engineered bone constructed with partially deproteinized biologic bone (PDPBB) and coculture of adipose-derived stem cells (ADSCs) and vascular endothelial cells (VECs) on host immune status, providing a very useful clue for the future development of bone engineering. METHODS: Tissue-engineered bones constructed by PDPBB and ADSCs, VECs or coculture of them were implanted into the muscle bag of bilateral femurs of Sprague-Dawley rats. Partially deproteinized biologic bone alone and blank control were also implanted. After transplantation, the proliferation of implanted seed cells in tissue-engineered bones was labeled by bromodeoxyuridine staining. Moreover, the changes of T-lymphocyte subpopulations, including CD3 + CD4+ and CD3 + CD8+ in peripheral blood were then detected using flow cytometry to analyze the immune rejection of tissue-engineered bone implantation based on peripheral blood CD4/CD8 ratios. RESULTS: After transplantation, the proliferation of implanted seed cells was observed in tissue-engineered bones of different groups. At different time points after transplantation, the CD4+/CD8+ ratio in peripheral blood of PDPBB + ADSCs, PDPBB + coculture, and blank control groups did not exhibit significant change. Although the CD4+/CD8+ ratio in peripheral blood of PDPBB + VECs group was significantly higher than other group at 1 week after transplantation, that of PDPBB + VECs and PDPBB + coculture group was significantly decreased at 8 week after transplantation compared with that of blank control group. CONCLUSIONS: Our results indicated that there was no significant immune rejection after transplantation of tissue-engineered bone constructed with PDPBB and coculture of ADSCs and VECs as seed cells.

Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig.

BACKGROUND: Varieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was to determine whether this animal can serve as a more effective osteoarthritis model and explore the role of SDF-1/CXCR4 signaling pathway in the development of Osteoarthritis in animals. METHODS: Twenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection, and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. Synovium was taken out for stromal cell-derived factor-1 analysis. RESULTS: Histopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II revealed an apparent reduction in this marker in the chemical groups compared with the other groups. CONCLUSIONS: These results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.

Potential of Forsythoside I as a therapeutic approach for acute lung injury: Involvement of TXNIP/NLRP3 inflammasome.

OBJECTIVE: To explore the role of Forsythoside I (FI) in acute lung injury (ALI) mouse and its underling mechanism. METHODS: The cell models of ALI are constructed by LPS induction. After pretreatment with different concentrations of FI, the lung injury is assessed by pathological changes of lung tissues and cell apoptosis. The cell viability, levels of pro-inflammatory cytokines, and the activation of TXNIP/NLRP3 pathway are inspected to investigate whether the effect of FI on inflammatory response is exerted by regulating the TXNIP/NLRP3 pathway. RESULTS: LPS induces inflammatory cell infiltration, tissue necrosis and pulmonary interstitial edema of mouse tissues, and LPS increases the protein concentration and levels of pro-inflammatory factors in mouse BALF. Additionally, enhanced cell apoptotic level, increased W/D ratio and MPO activity, as well as suppressed SOD activity are observed in LPS-induced mouse models. Those inflammation response, oxidative stress and lung injury can be attenuated by FI (12.5 mg/kg, 25 mg/kg, 50 mg/kg) in a dose-dependent manner. Meanwhile, both in vitro and in vivo studies reveal that FI can lead to suppressed TXNIP expression and inactivated NLRP3 inflammasomes. TXNIP is an upstream target of NLRP3, and FI mitigates ALI by decreasing TXNIP to block NLRP3 inflammasomes. CONCLUSION: FI protects against ALI through the mediation of TXNIP/NLRP3 inflammasome axis and therefore has a certain potential for ALI treatment.

A novel method to establish the rabbit model of knee osteoarthritis: intra-articular injection of SDF-1 induces OA.

BACKGROUND: Animal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. However, these methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA. METHODS: Our studies attempted to find a rapid, easy, and consistent with the natural pathological process of OA modeling method by intra-articular injection of stromal cell-derived factor 1 (SDF-1) in the rabbit knee. After induction we collected cartilage specimens from the medial femoral condyle to undergo macroscopic, histological, immunohistochemical, and biochemical evaluations. Meanwhile, compared with Hulth surgical method to evaluate its efficacy. RESULTS: Macroscopic observation and modified Mankin score of histological staining exhibited typical features of middle stage OA cartilage in SDF-1 injected groups. Immunohistochemically, the positive expression of interleukin-1 (IL-1) and tumor necrosis factor α(TNF-α) was earlier and higher in high dose SDF-1 group than the surgical group. The matrix metalloproteinases (MMPs) in synovial fluid and chondrocytes significantly increased, but type II collagen (COLII) and aggrecan (ACAN) protein expressions decreased in SDF-1 injected group following the extension of time and increase of SDF-1 concentration. CONCLUSIONS: Our data indicated intra-articular injection of SDF-1 (40µg/kg, three times for 12 weeks) can induce rabbit knee OA model successfully more rapidly and easily than traditional surgical modeling. The study provided a further option for the establishment of knee OA animal model.

Interleukin-1ß-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling.

BACKGROUND: Interleukin-1ß (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown. METHODS: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation. RESULTS: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice. CONCLUSION: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.

Microglia exosomal miRNA-137 attenuates ischemic brain injury through targeting Notch1.

Microglia are the resident immune cells in the central nervous system and play an essential role in brain homeostasis and neuroprotection in brain diseases. Exosomes are crucial in intercellular communication by transporting bioactive miRNAs. Thus, this study aimed to investigate the function of microglial exosome in the presence of ischemic injury and related mechanism. Oxygen-glucose deprivation (OGD)-treated neurons and transient middle cerebral artery occlusion (TMCAO)-treated mice were applied in this study. Western blotting, RT-PCR, RNA-seq, luciferase reporter assay, transmission electron microscope, nanoparticle tracking analysis, immunohistochemistry, TUNEL and LDH assays, and behavioral assay were applied in mechanistic and functional studies. The results demonstrated that exosomes derived from microglia in M2 phenotype (BV2-Exo) were internalized by neurons and attenuated neuronal apoptosis in response to ischemic injury in vitro and in vivo. BV2-Exo also decreased infarct volume and behavioral deficits in ischemic mice. Exosomal miRNA-137 was upregulated in BV2-Exo and participated in the partial neuroprotective effect of BV2-Exo. Furthermore, Notch1 was a directly targeting gene of exosomal miRNA-137. In conclusion, these results suggest that BV2-Exo alleviates ischemia-reperfusion brain injury through transporting exosomal miRNA-137. This study provides novel insight into microglial exosomes-based therapies for the treatment of ischemic brain injury.

Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction.

BACKGROUND: Cerebral infarction ranks as the second leading cause of disability and death globally, and inflammatory response of glial cells is the main cause of brain damage during cerebral infarction. METHODS: Studies have shown that mesenchymal stem cells (MSCs) can secrete exosomes and contribute to cerebral disease. Here, we would explore the function of MSC-derived exosome in cerebral infarction. RESULTS: Microarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion (MCAO) mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4. Then, we injected AAV9-miR-542-3p into paracele of sham or MCAO mice. Functional analysis showed that AAV9-miR-542-3p inhibited infarction area and the number of degenerating neurons and suppressed inflammatory factors' expression and inflammatory cell infiltration. As well, transfection of miR-542-3p mimics into HA1800 cells underwent oxygen and glucose deprivation (OGD). Similarly, overexpression of miR-542-3p alleviated OGD induced cell apoptosis, ROS, and activation of inflammation response. Moreover, miR-542-3p could be packaged into MSCs and secreted into HA1800 cells. The extractive exosome-miR-21-3p treatment relieved MCAO- or OGD-induced cerebral injury and inflammation through targeting TLR4. CONCLUSION: These results confirmed that MSC-derived exosome miR-542-3p prevented ischemia-induced glial cell inflammatory response via inhibiting TLR4. These results suggest possible therapeutic strategies for using exosome delivery of miR-542-3p to cure cerebral ischemic injury.

A non-inferiority comparison of Delta Medical's PEEK Suture Anchor and Smith & Nephew's PEEK Suture Anchor in arthroscopic rotator cuff repair: a multicenter prospective single-blind randomized controlled clinical trial.

BACKGROUND: To compare the early clinical outcomes and Magnetic Resonance Imaging (MRI) results of Delta Medical's PEEK (polyether ether ketone) suture anchor with those of Smith & Nephew's PEEK suture anchor in patients with arthroscopic rotator cuff repair. METHODS: A total of 106 patients in four different medical centers were randomly allocated into two groups: Delta Medical's PEEK suture anchor (53 patients); Smith & Nephew's PEEK suture anchor (53 patients). The MRI results and early clinical outcomes were evaluated at 3 and 6 months postoperatively. The University of California at Los Angeles (UCLA) shoulder rating scale and the visual analog scale (VAS) score for pain and range of motion were evaluated. MRI were performed at 3 and 6 months postoperatively to examine the integrity of the repaired rotator cuff tendon based on the Sugaya classification. RESULTS: Significant improvements in pain relief, shoulder function, and functional scores were observed in both groups after surgery regardless of the suture anchor applied (P<0.001). No differences observed in the functional scores and range of motion. The assessments of UCLA scores at 3 and 6 months produced no statistical differences (P=0.885 and 0.340, respectively). The mean VAS scores in group 1 did not reveal statistical differences at 3 and 6 months after surgery compared to group 2. No significant differences in the range of motion were found at each follow-up time-point and no shifting or breakage of the anchors occurred between the two groups (P>0.01). No major intra- or post-operative complications, such as infection, and vessel or nerve injury. CONCLUSIONS: Pain relief and shoulder function were improved after complete rotator cuff repair in both groups, regardless of the suture anchor applied. The difference in functional scores and range of motion were not significant in groups 1 and 2. Delta Medical's PEEK suture anchor had a non-inferiority effect compared to Smith & Nephew's PEEK suture anchor. Delta Medical's PEEK suture anchor was suitable for arthroscopic rotator cuff repair. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100051716.