Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Identification of retinal thickness and blood flow in age-related macular degeneration with reticular pseudodrusen.

AIM: To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen (RPD) as an early detection strategy for age-related macular degeneration (AMD). METHODS: This retrospective study included 24 subjects (33 eyes) with RPD and 25 heathy control subjects (34 eyes). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) of the retinal posterior poles were investigated with optical coherence tomography angiography (OCTA). Retinal thicknesses and vessel densities were analyzed statistically. RESULTS: The general retinal thicknesses of RPD eyes were significantly decreased (95%CI -14.080, -0.655; P=0.032). The vessel densities of DCP in RPD eyes were significantly increased in the global (95%CI 1.067, 7.312; P=0.027), parafoveal (95%CI 0.417, 5.241; P=0.022), and perifoveal (95%CI 0.181, 6.842; P=0.039) quadrants. However, the vessel densities of the SCP were rarely increased in the eyes with RPD. CONCLUSION: The thinning of retinas in the RPD group suggests a reduction in the number of cells. Additionally, the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply, possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina. This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.

TACC diagnosed by transoesophageal endoscopic ultrasonography: A case report.

BACKGROUND: Primary adenoid cystic carcinoma in the trachea (TACC) is a rare tumour. Tracheal bronchoscopy is always chosen as a routine approach to obtain a pathological diagnosis, but it can be associated with an increased risk of asphyxia. CASE SUMMARY: We describe a case of TACC in a patient evaluated by chest computed tomography (CT) with three-dimensional reconstruction imaging and diagnosed by transoesophageal endoscopic ultrasonography. The pathological diagnosis confirmed tracheal adenoid cystic carcinoma. CONCLUSION: We highlight the importance of CT and provide a successful exploration of transoesophageal biopsy as a safe alternative approach.

Clinical Application of the Musculoperiosteal Iliac Flap for Osteonecrosis of the Femoral Head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) often affects young, active patients, and the femoral head's preservation is the primary goal of treatment for this disease. Vascularized iliac crest bone grafting is one of the many vascularized procedures used in treating ONHF. In some cases, we selectively performed this procedure using the musculoperiosteal iliac flap with the ascending branch of the lateral femoral circumflex artery for ONFH treatment. METHODS: Twelve patients (12 hips) with nontraumatic femoral head necrosis underwent musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery. The Harris Hip Score (HHS), visual analog scale score, and double-hip X-ray findings were used to analyze hip function changes within 10 days preoperatively and 6 and 12 months postoperatively. RESULTS: The mean HHS increased from 52.33 ± 3.34 preoperatively to 65.92 ± 5.04 6 months postoperatively and 79.75 ± 3.84 12 months postoperatively, and the data showed a statistical significance difference between preoperative and postoperative (F = 131.90, P < 0.01). The HHS at 6 and 12 months after surgery were significantly different (P < 0.01). The visual analog scale score showed the same trend. The x-ray of hip joints at 6 and 12 months after surgery showed that the femoral heads' shape and contour were good, femoral heads did not collapse, and the transferred bone flaps healed well. CONCLUSIONS: Musculoperiosteal iliac flap transfer with the ascending branch of the lateral femoral circumflex artery may be an effective method with a high clinical success rate for treating young patients with early to midstage ONFH.

Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model.

Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.

Biocompatible Porous Tantalum Metal Plates in the Treatment of Tibial Fracture.

Fractures of the tibia represent a common class of injuries in orthopedics. The blood supply to the tibia is poor due to the small subcutaneous muscle tissues inside. Consequently, the tibia is prone to delayed fracture healing and nonunion of the fracture after surgery. In this case, we used porous tantalum metal plate to treat nonunion of a tibial fracture and achieved satisfactory therapeutic effects. For the first time in the field, we used 3D printing technology to fabricate porous tantalum metal plates for the treatment of tibial fractures. The resulting porous tantalum metal exhibited excellent mechanical and biological properties, and improved the therapeutic effects for the treatment of a tibial fracture nonunion. Porous tantalum metal plates have great application potential as a new implant material for internal fixation.

Micro Perfusion and Quantitative Analysis of the Femoral Head Intraosseous Artery.

The present study investigates the feasibility of micro perfusion of femoral head specimens from femoral neck fracture patients by the inferior retinacular arteries and performing intraosseous artery quantitative analysis of the femoral head. Twelve femoral neck fracture patients who had undergone conventional hip replacement surgery were included in this study. Femoral head specimen arteries were first dissected and exposed and then perfused by the inferior retinacular arteries and all the femoral heads underwent micro-CT scanning. After micro-CT scanning, a digital 3-D model was reconstructed to quantify the femoral head intraosseous arteries for comparison with a normal femoral head. The artery length density, artery volume density, and artery length/volume ratio were calculated separately and compared with normal femoral head parameters. Micro-CT scanning displayed the epiphyseal arterial network structure and their fine vascular branches in all 12 femoral neck fractures. Blood was supplied from the inferior retinacular artery to the epiphyseal arterial network then to all the fine blood vessels within the femoral head. No statistical differences were observed in femoral heads' intraosseous artery length densities or volume densities between the normal and femoral neck fracture specimens, while the artery length/volume ratio showed a statistical difference, and the ratio increased from 19 to 46. Micro perfusion of the femoral head by the inferior retinacular arteries is possible and can present the epiphyseal network and their fine arterial branches in pathologic conditions to provide a morphological basis for the study of femoral head disease.

Effect of superior retinacular artery damage on osteonecrosis of the femoral head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is the result of dysfunctional blood supply, but associations between specific damaged arteries, imaging changes and clinical sign require more understanding. We investigated characteristics of ONFH that pertain to blood supply, imaging appearance, and clinical feature to judge the prognosis of ONFH. METHODS: Clinical data were collected for 92 patients (118 hips) with ONFH, including gender, age, duration of pain (from initial clinical presentation to arthroplasty), cause, stage, and classification. Magmatic resonance imaging and X-rays were obtained of all patients to diagnose ONFH. The sizes of lesions were classified by necrotic index. The location of necrosis was classified as Type A, B, or C using the grading system by magmatic resonance imaging and X-rays. All hips were imaged with digital subtraction angiography to visualize their blood-supply characteristics. Hips were divided into groups based on the source artery for femoral head damage: superior retinacular artery (S), inferior retinacular artery (I), and combined superior and inferior retinacular arteries (S+I). Via digital subtraction angiography, imaging appearances and clinical data in three groups were compared. RESULTS: ONFH was caused by damage in either the superior or inferior retinacular artery, or both, in all of 118 hips. The group with only inferior retinacular artery damage reported longer hip pain duration than the other groups. The probability of the lesion extending laterally to the acetabular edge in group S was much more than it in group I. Necrosis indices of the patients in S and S+I were higher than those in group I. CONCLUSIONS: ONFH associated with interruption of the superior and inferior retinacular arteries in this study. When the former alone was damaged, the necrosis of the volume was larger, the risk of femoral head collapse was higher and the time from initial clinical presentation to arthroplasty was shorter.

Prospective and comparative analysis of internal fixation of femoral neck fractures with or without vascularized iliac graft in young adults.

The purpose of this study was to compare the effectiveness of 2 surgical approaches for femoral neck fractures in young adults: internal fixation with or without a vascularized iliac graft. Between January 1998 and December 2008, seventy-eight patients presented with a Garden type III (n=38) or IV (n=40) femoral neck fracture. Thirty-eight patients were women and 40 were men, with an average age of 28 years (range, 16-38 years). Fractures were caused by fall injury (n=24), motor vehicle accident (n=36), and heavy weight lifting (n=18). Patients were randomly divided into 2 groups. Group A underwent internal fixation with 2 cannulated compression screws combined with an iliac graft supported by the ascending branch of the lateral femoral circumflex artery (n=44), and group B underwent internal fixation with 3 cannulated compression screws (n=34). Average follow-up was 4.5 years (range, 2-8 years), and mean Harris Hip Score was 92 (range, 62-100) in group A and 84 (range, 40-100) in group B. Average fracture healing time at final follow-up was 4.4 months in group A and 6 months in group B. Two (4.5%) cases of osteonecrosis of the femoral head occurred in group A, and 8 (23.5%) cases occurred in group B. Internal fixation with 2 cannulated compression screws combined with an iliac graft supported by the ascending branch of the lateral femoral circumflex artery is an effective surgical approach for treating femoral neck fractures in young adults to minimize the occurrence of fracture nonunion and osteonecrosis of the femoral head and to facilitate bone healing and functional recovery of the hip.

Anti-inflammation effects of corn silk in a rat model of carrageenin-induced pleurisy.

Pleurisy is an inflammation of the pleural layers that surround the lungs. Despite much research into inflammatory diseases, no drugs with favorable safety profiles are available yet for their treatment. Corn silk has been used in many parts of the world for the treatment of edema, cystitis, gout, kidney stones nephritis, and prostitutes. However, no scientific reports on the anti-inflammatory effects of corn silk were so far available. To test the anti-inflammatory efficacy of corn silk extract (CSEX) in a rat model of carrageenin (Cg)-induced pleurisy, exudate formation, and cellular infiltration, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), vascular endothelial growth factor alpha (VEGF-α), interleukin-17 (IL-17), C3 and C4 complement protein levels, adhesion molecule (ICAM-1) and inducible nitric oxide synthase (iNOS) levels, nuclear factor kappa B (NF-κB) activation, and total antioxidant activity were studied, respectively. Pretreatment with CSEX reduced Cg-induced pleurisy exudate, number of leukocytes, oxidative stress, C3 protein level, and O (2)(-) levels at the inflammatory site. Pretreatment with CSEX also inhibited TNF-α, IL-1ß, VEGF-α, and IL-17A and blocked inflammation-related events (ICAM-1 and iNOS) by activation of NF-κB. Supplementation with CSEX may be a promising treatment for inflammatory diseases that involve oxidative stress.

Trace elements analysis of urine and hair in tuberculous pleurisy.

In this study, copper, zinc, magnesium, manganese, selenium, and iron of urine and hair were measured in the patients with tuberculous (TB) pleurisy (n = 24) and in the control group (n = 20). Selenium, magnesium, and zinc of hair were found to be significantly lower in TB pleurisy cases than those in the control group (p < 0.05, p < 0.001, and p < 0.01, respectively). On the contrary, selenium and magnesium of urine were found to be significantly elevated in TB pleurisy cases than those in the control group (p < 0.05 and p < 0.001, respectively). There was no significant difference in the value of manganese and iron between TB pleurisy and the control group (p > 0.05). Copper level were significantly increased in hair and decreased in urine of the patients (p < 0.01). The occurrence of these abnormalities constitutes new information regarding trace elements in TB pleurisy patients. These results may provide an additional disease correlate for assessing TB pleurisy risk.

[Treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow stromal stem cells under arthroscope].

OBJECTIVE: To understand the biological characteristics and osteogenic potential of hVEGF-165 gene modified marrow stromal stem cells and investigate the effect and value of treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow stromal stem cells under arthroscope. METHODS: rAAV-2-hVEGF-165 plasmids were extracted and transfected into rabbit marrow stromal stem cells. hVEGF-165 mediated by adeno-associated virus (AAV) was used to transfect rMSCs. The transfection efficiency was detected with enhanced green fluorescent protein under fluorescence microscope. hVEGF-165 mediated by adeno-associated virus (AAV) was used to transfect rMSCs. Virus transfection stayed overnight after 90% cell converged. MOI was 105. The transcription and expression of hVEGF-165 protein expression were detected by RT-PCR and Western blot. The necrotic bone was emptied and then MSCs were implanted under arthroscope. The histology of femoral head was inspected at postoperative 2 - 8 weeks. RESULTS: The expression of hVEGF-165 gene could be found distinctly in the transfected rabbit MSCs and hVEGF-165 protein in the supernatants of transfected cell cultures. The transfection efficiency of adeno-associated virus (AAV) transfected rMSCs was 70%. And rAAV-2-hVEGF-165 transfected rMSCs achieved an effective expression by RT-PCR and Western blot. hVEGF-165 could be found after a 48-hour transfection and peaked at Day 10. Immunohistochemical detection showed that the implanted rMSCs was positive at Week 2 and strong positive at Week 8. The compressive strength of the hVEGF-165 gene group approached that of normal control. CONCLUSION: hVEGF-165 gene transfected rabbit MSCs can express hVEGF-165 with highly biological activity. It provides provided a basis for employing hVEGF-165 gene and MSCs based gene therapy for ONFH repairing and regeneration. rAAV-2-hVEGF-165/MSCs may be implanted accurately under arthroscope. Implantation of human BMP-2 gene transfected BMSCs can repair early-stage experimental femoral head necrosis.

Meconium-stained liquor during labor is associated with raised neonatal cord blood 8-iso-prostaglandin F2alpha concentration.

OBJECTIVE: The purpose of this study was to compare the umbilical arterial 8-iso-prostaglandin F2alpha, concentrations between pregnancies that were complicated by moderate or thick meconium-stained liquor and those with clear liquor. STUDY DESIGN: Umbilical cord arterial blood samples were collected from 247 singleton pregnancies with either moderate or thick meconium-stained liquor at any stage of labor or clear liquor at all stages of labor for the determination of the total 8-iso-prostaglandins F2alpha concentration. RESULTS: The median total 8-iso-prostaglandins F2alpha concentration of the meconium-stained liquor group was significantly higher than that of the control group (719.2 vs 115.8 pg/mL). Among the meconium-stained liquor group, those who had a change from "clear liquor" at early labor to "moderate/ thick meconium-stained liquor" at late first stage or at delivery (late meconium-stained liquor group) had higher 8-iso-prostaglandins F2alpha concentration, compared with those who had moderate/ thick meconium-stained liquor since early labor (early meconium-stained liquor group; 959.8 vs 499.9 pg/mL). With the use of multiple regression analysis, meconium-stained liquor, duration of second stage of labor, and abnormal fetal heart tracings were independent determinants of cord blood 8-iso-prostaglandins F2alpha concentration. CONCLUSION: Moderate or thick meconium-stained liquor is an independent factor for increased oxidative stress in pregnancy.