Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-ß-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.

Topical Use of Low-dose Tranexamic Acid Has no Effect on Drainage Volume after Medial Open Wedge High Tibial Osteotomy: A Case Control Study.

OBJECTIVE: Many studies reported that tranexamic acid (TXA) was effective in reducing surgical blood loss in the perioperative period of medial open wedge high tibial osteotomy (MOWHTO). However, few studies focused on the simple topical use of TXA in MOWHTO, and the modality and dosage of topical use of TXA varied. The purpose of this study was to observe the effect of topical use of low-dose TXA on drainage volume after MOWHTO, and to analyze the related influencing factors. METHODS: Data of patients who underwent MOWHTO combined with arthroscopic knee surgery in our department from January 2019 to September 2021 were retrospectively analyzed. A total of 105 patients (38 males and 67 females, aged 57.7 ± 7.5 years) were included in this study who received topical TXA or no TXA. The patients were divided into three groups: control group (39 cases), 0.5 g TXA group (40 cases), 1 g TXA group (26 cases). Postoperative drainage volume, wound healing, incidence of hematoma and deep venous thrombosis (DVT) were observed and analyzed in the three groups. The effects of gender, hypertension and diabetes on postoperative drainage volume were analyzed using a t-test. The correlation between age, body mass index (BMI), osteotomy gap and postoperative drainage volume were analyzed using the Pearson correlation coefficient. RESULTS: The average postoperative drainage volume of the control group was 259.54 ± 226.33 mL, that of the 0.5 g TXA group was 277.18 ± 177.68 mL, and that of the 1 g TXA group was 229.15 ± 219.93 mL. There was no statistically significant difference in postoperative drainage volume among the three groups (F = 0.423, p = 0.656). There was no local hematoma and wound infection in the three groups. The wound fat liquefaction was found in one patient of the control group. The incidence of DVT was 38.9% (7/18) and 57.1% (8/14) in the control group and 0.5 TXA group, respectively. There was no significant difference in the incidence of DVT between the above two groups (p = 0.476). The average postoperative drainage volume of male patients in the three groups was higher than that of female patients, and the differences were statistically significant (p < 0.05). There was no correlation between age, BMI, osteotomy gap and postoperative drainage volume in the three groups (p > 0.05). CONCLUSION: Topical use of low-dose TXA has no significant effect on drainage volume after MOWHTO. The drainage volume after MOWHTO in male patients was more than that in female patients. Topical administration of low-dose TXA does not increase postoperative complications, such as DVT and hematoma.

[Study on clinical characteristics and surgical methods of bucket-handle meniscal tears].

Objective: To summarize the clinical features, surgical methods, and prognosis of bucket-handle meniscal tears (BHMTs), and provide guidance for clinical treatment. Methods: The clinical data of 91 BHMTs patients (91 knees), who met the selection criteria and were admitted between January 2015 and January 2021, was retrospectively analyzed. There were 68 males and 23 females. Age ranged from 16 to 58 years with an average of 34.4 years. The injury was caused by sports in 68 cases, traffic accident in 15 cases, and falls or sprains in 8 cases. There were 49 cases of left knee injury and 42 cases of right knee injury. The time from the onset of symptoms to the admission ranged from 1 day to 13 months (median, 18 days), including >1 month in 35 cases and ≤1 month in 56 cases. Medial BHMTs occurred in 52 cases and lateral BHMTs in 39 cases. There were 36 cases with ACL rupture and 12 cases with discoid meniscus. The knee extension was limited more than 10° in 55 cases. According to the condition of meniscus injury, the meniscus suture with Inside-out combined with All-inside techniques (54 cases) or meniscoplasty (37 cases) under arthroscopy were selected. ACL reconstruction was performed in all patients with ACL rupture with autogenous hamstring tendon. Postoperative complications were observed. International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner score were used to evaluate knee function, and clinical failure was recorded. Results: Two patients developed intermuscular venous thrombosis, which improved after oral anticoagulant therapy. No vascular injury, postoperative infection, joint stiffness, or other complications occurred in all patients. All patients were followed up 24-95 months, with a median of 64 months. A total of 12 cases (13.19%) failed the operation and were re-operated or given oral anti-inflammatory analgesics and rehabilitation therapy. At last follow-up, IKDC score and Lysholm score of 91 patients significantly increased when compared with those before operation ( P<0.05), while Tegner score significantly decreased ( P<0.05). The above indexes of patients treated with meniscus suture and meniscoplasty were also significantly different from those before operation ( P<0.05). Conclusion: BHMTs occurs mostly in young men and is one of the important reasons for the limitation of knee extension after trauma. Arthroscopic meniscus suture and meniscoplasty can obtain good effectiveness according to individual conditions of patients. But the latter can better preserve the shape and function of meniscus, and theoretically can obtain better long-term outcomes, which needs to be confirmed by further research with larger sample size.

Research on nonlinear response analysis of micro-cracks under vibro-acoustic modulation.

In view of the complex nonlinear interaction mechanism between acoustic waves and damage in vibration sound modulation technology, this paper derives the kinematic equilibrium equation for linear elastic materials with cracks undergoing infinitesimal deformation using structural mechanics theory. The weak form of the equation is derived by applying the principle of virtual work to calculate the virtual work due to nonlinear changes in crack spacing. This paper also explains the physical origin of high harmonic and sideband signals in the system displacement solution. In addition, a three-dimensional contact model of micro-cracks is constructed to describe the nonlinear effect of contact sound on the crack surface caused by relevant displacement fields. To verify the correctness of the model, two indicators, the modulation index and the damage index, are used to evaluate the simulation results. The results indicate that the interface contact under micro-crack opening and closing motions causes additional nonlinear frequencies and that the nonlinear response increases with excitation amplitude while being relatively sensitive to micron-level cracks. Finally, experimental research is conducted, which confirms the theoretical derivation, and the reliability of the model has been verified.

Arthroscopy combined with high tibial osteotomy promotes cartilage regeneration in osteoarthritis.

BACKGROUND: To investigate the effect of arthroscopy combined with high tibial osteotomy (HTO) on cartilage regeneration in patients with knee osteoarthritis. METHODS: A retrospective analysis of 50 patients with varus and medial compartment osteoarthritis of the knee treated by arthroscopy combined with HTO. One year after the operation, a second-look arthroscopy was performed to observe the cartilage regeneration. The regeneration of cartilage was evaluated by different pathological staining of some of the new cartilage. Finally, part of the new cartilages (n = 6) were taken for quantitative real-time PCR and western blotting experiments to display the mechanism of cartilage regeneration. RESULTS: One year after arthroscopy combined with HTO, the results of arthroscopy revealed the formation of new tissue in the defect area of the medial compartment's cartilage in the knee joint. In addition, different pathological staining results indicated that the new tissue was cartilage-like tissue. Furthermore, HTO potently up-regulated the expression of p-ERK1/2 at the protein level in knee osteoarthritis patients compared with control group. However, there was no significant difference in the relative expression of collagen II at mRNA and protein level between control group and knee osteoarthritis patients. CONCLUSION: Arthroscopy combined with HTO can promote cartilage regeneration in patients with knee osteoarthritis.

[Management status of anterior cruciate ligament injury in children and adolescents].

Objective: To summarize the current management of anterior cruciate ligament (ACL) injury in children and adolescents, in order to provide reference for the management of ACL injury in children and adolescents. Methods: The relevant literature at home and abroad in recent years was extensively accessed to summarize the management status of ACL injury in children and adolescent. Results: The number of ACL injury in children and adolescents is increasing every year. The diagnosis of ACL mainly depends on symptoms and signs. Rehabilitation, physeal-sparing techniques, partial transphyseal techniques, all-epiphyseal techniques, and transphyseal techniques are used to treat ACL injury in children and adolescents. Conclusion: Dynamic monitoring of knee joint in children and adolescents should be strengthened. The best treatment for ACL injury in children and adolescents is selected according to the patients' actual age, bone age, Tanner stage, and physiological conditions such as menstruation, body growth speed, and other characteristics.

[Experience in diagnosis and treatment of KD- â ¢M dislocation of knee joint].

OBJECTIVE: To explore the effectiveness of one-stage posterior medial corner (PMC) repair or reconstruction combined with anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction in treating KD-ⅢM dislocation. METHODS: The clinical data of 15 patients with knee KD-ⅢM dislocation who met the selection criteria between January 2016 and July 2019 were retrospectively analyzed. There were 9 males and 6 females, aged 22-61 years (mean, 40.3 years). Injuries were caused by violence of flexion, valgus, and external rotation, including 10 cases of traffic accident injuries, 3 cases of crush injuries, 1 case of winch injury, and 1 case of explosion injury. The time from injury to operation ranged from 3 days to 6 months, with an average of 18.5 days. PMC repair combined with PCL+ACL reconstruction was performed in 10 cases in acute stage (within 3 weeks after injury), including 3 cases of irreducible dislocation. PMC+PCL+ACL reconstruction was performed in 5 cases with chronic dislocation. Before operation and at last follow-up, the knee joint function was evaluated by Lysholm score and International Knee Documentation Committee (IKDC) 2000 score. KT-3000 was used to evaluate the forward stability of the knee (calculated the difference of tibial anterior displacement of both knees), the X-ray films of the stress position of the knee joint was used to evaluate the valgus of the knee (calculated the difference of medial joint space width of both knees) and the backward stability (calculated the difference of tibial posterior displacement of both knees), and the internal and external rotation stability was evaluated by knee flexion 30° tibial external rotation and knee flexion 90° tibial internal rotation tests (calculated the difference of tibial internal rotation and the difference of tibial external rotation of both knees). RESULTS: The operation time was 120-240 minutes, with an average of 186.5 minutes. Patients were followed up 24-48 months, with an average of 27.4 months. There was no complication such as infection, deep vein thrombosis, vascular injury, or heterotopic ossification. At last follow-up, the Lysholm score, IKDC2000 score, the difference of tibial anterior displacement of both knees, the difference of medial joint space width of both knees, the difference of tibial posterior displacement of both knees, the difference of tibial internal rotation and the difference of tibial external rotation of both knees significantly improved when compared with preoperative ones ( P<0.05). According to the IKDC2000 valgus stability grading standard, there were 3 cases of grade C and 12 cases of grade D before operation, and 10 cases of grade A and 5 cases of grade B at last follow-up, which was significantly improved when compared with that before operation ( Z=-4.930, P=0.000). At last follow-up, the pivot shift tests of 15 patients were negative. The anterior and posterior drawer tests of 10 patients were negative, 5 patients had mild instability, both the anterior and posterior drawer tests were positive. CONCLUSION: KD-ⅢM dislocation of the knee joint can lead to the posterior medial and anterior instability. Acute dislocation combined with "dimple sign" requires surgical reduction as soon as possible to repair PMC and reconstruct PCL and ACL. In chronic patients, PMC is difficult to repair, it is recommended to reconstruct PMC, PCL, and ACL at one stage to improve knee joint stability. The early and middle effectiveness are satisfactory.

Gray matter volume reduction with different disease duration in trigeminal neuralgia.

PURPOSE: Structural magnetic resonance imaging is widely used to explore brain gray and white matter structure in trigeminal neuralgia (TN) but has yielded conflicting findings. This study investigated the relationship between disease duration as a clinical feature of TN and changes in brain structure. METHODS: We divided 49 TN patients into three groups (TN1-TN3) based on disease duration (TN1 = 1.1 ± 0.7 (0-2) years, TN2 = 4.8 ± 1.5 (3-7) years, TN3 = 15.1 ± 5.5 (10-30) years). We used voxel-based morphometry (VBM) to compare the gray matter volume (GMV) across groups and between TN patients and 18 matched healthy control subjects. RESULTS: The TN1 group showed reduced GMV of pain-related regions in the cerebellum; the TN2 group showed reduced GMV in the thalamus and the motor/sensory cortex; and the TN3 group showed reduced GMV in the emotional and reward circuits compared with healthy controls. Similar brain regions, including bilateral hippocampi, caudate, left insular cortex, and medial superior frontal cortex, were affected in TN2 and TN3 compared with TN1. CONCLUSION: Disease duration can explain differences in structural alterations-especially in pain-related brain regions-in TN. These results highlight the advanced structural neuroimaging method that are valuable tools to assess the trigeminal system in TN and may further our current understanding of TN pathology.

Research on sound power measurement of multi-element ultrasonic focusing transducer based on cross-spectrum method.

In this paper, aiming at the problem that a multi-array focused ultrasonic transducer working in a high power range has a nonlinear influence on the measurement accuracy, a study of acoustic power measurement based on the near field cross-spectrum method was carried out. The focused acoustic field of a multi-array transducer was derived theoretically by combining the cross-spectrum method and the Westervelt nonlinear acoustic propagation equation. Finite element simulation was used to establish the model of the focused sound field of the multi-array transducer under different excitation conditions, and the influence law of each harmonic on the total sound power under specific excitation conditions was obtained. A cross-spectrum measurement system was built to scan the two near focusing planes under different excitation conditions. The total energy, each harmonic energy, and their proportion in the focusing region under the corresponding excitation were obtained through calculation and processing. The theoretical and simulation results were verified, and the harmonic energies were compensated in the calculation of the total ultrasonic power. The measurement results were compared with those obtained by radiation force balances. It was found that the maximum measurement deviation of compensated ultrasonic power was 7.89%, which met the requirements of acoustic measurement. The accuracy of the method and conclusion was verified under the power range of 10-60 W.

Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence.

BACKGROUND: Application of mesenchymal stem cell-derived exosomes (MSC-EXO) has emerged as a novel therapeutic strategy for myocardial infarction (MI). Our previous study showed that pretreatment with hemin, a potent heme oxygenase-1 (HO-1) inducer, enhanced the cardioprotective effects of MSCs in a mouse model of MI. This study aimed to investigate the therapeutic effects of EXO derived from hemin-pretreated MSCs (Hemin-MSC-EXO) in MI and explore the potential mechanisms. METHODS: MSC-EXO and Hemin-MSC-EXO were collected and characterized. MSC-EXO and Hemin-MSC-EXO were intramuscularly injected into the peri-infarct region in a mouse model of MI. Heart function of mice was assessed by echocardiography. The mitochondrial morphology of neonatal mice cardiomyocytes (NMCMs) under serum deprivation and hypoxic (SD/H) conditions was examined by Mitotracker staining. The cellular senescence of NMCMs was determined by senescence-associated-ß-galactosidase assay. A loss-of-function approach was adopted to determine the role of Hemin-MSC-exosomal-miR-183-5p in the regulation of cardiomyocyte senescence RESULTS: EXO were successfully isolated from the supernatant of MSCs and Hemin-pretreated MSCs. Compared with MSC-EXO, injection of Hemin-MSC-EXO significantly improved cardiac function and reduced fibrosis. Both MSC-EXO and Hemin-MSC-EXO ameliorated cardiomyocyte senescence and mitochondrial fission in vitro and in vivo, and the latter exhibited better protective effects. MicroRNA sequencing revealed a higher level of miR-183-5p in Hemin-MSC-EXO than in MSC-EXO. MiR-183-5p knockdown partially abrogated the protective effects of Hemin-MSC-EXO in attenuating mitochondrial fission and cellular senescence of cardiomyocytes induced by SD/H. High mobility group box-1 (HMGB1) abundance was lower in Hemin-MSC-EXO-treated than MSC-EXO-treated mouse hearts, and HMGB1 was identified as one of the potential target genes of miR-183-5p. Mechanistically, Hemin-MSC-EXO inhibited SD/H-induced cardiomyocyte senescence partially by delivering miR-183-5p into recipient cardiomyocytes via regulation of the HMGB1/ERK pathway. Furthermore, knockdown of miR-183-5p reduced the Hemin-MSC-EXO-mediated cardioprotective effects in a mouse model of MI. CONCLUSION: Our results reveal that Hemin-MSC-EXO are superior to MSC-EXO in treating MI. Exosomal miR-183-5p mediates, at least partially, the cardioprotective effects of Hemin-MSC-EXO by inhibiting cardiomyocyte senescence via regulation of the HMGB1/ERK pathway. This study highlights that MSC-EXO have high translational value in repairing cardiac dysfunction following infarction.

Apelin Rejuvenates Aged Human Mesenchymal Stem Cells by Regulating Autophagy and Improves Cardiac Protection After Infarction.

The protective effects of mesenchymal stem cell (MSC)-based therapy for myocardial infarction (MI) are largely hampered as they age. Apelin is an endogenous ligand of its receptor APJ and plays an essential role in regulating multiple biological activities including MSC proliferation and survival. In this study, we investigated whether Apelin regulates MSC senescence and whether its overexpression could rejuvenate aged MSCs (AMSCs) to improve cardiac protection following infarction in mice. MSC senescence was evaluated by senescence-associated ß-galactosidase assays. Apelin level was examined by western blotting. Autophagy was determined by transmission electron microscopy. The cardioprotective effect of AMSCs with Apelin overexpression (Apelin-AMSCs) was assessed in a mouse MI model. Apelin expression was dramatically reduced in AMSCs. Interestingly, knockdown of Apelin induced young MSCs (YMSC) senescence, whereas overexpression rescued AMSC senescence. Apelin overexpression also increased AMSC angiogenic capacity. Mechanistically, Apelin overexpression upregulated the autophagy level of AMSCs by activating AMP-activated protein kinase (AMPK) signaling, thereby rejuvenating AMSCs. Compared with AMSCs, transplantation of Apelin-AMSCs achieved better therapeutic efficacy for MI by enhancing cell survival and angiogenesis. In conclusion, our results reveal that Apelin activates AMPK to rejuvenate AMSCs by increasing autophagy and promotes cardioprotection following infarction in mice. This study identified a novel target to rejuvenate AMSCs and enhance their therapeutic efficacy.

Study on the Evaluation Method of Sound Phase Cloud Maps Based on an Improved YOLOv4 Algorithm.

Most sound imaging instruments are currently used as measurement tools which can provide quantitative data, however, a uniform method to directly and comprehensively evaluate the results of combining acoustic and optical images is not available. Therefore, in this study, we define a localization error index for sound imaging instruments, and propose an acoustic phase cloud map evaluation method based on an improved YOLOv4 algorithm to directly and objectively evaluate the sound source localization results of a sound imaging instrument. The evaluation method begins with the image augmentation of acoustic phase cloud maps obtained from the different tests of a sound imaging instrument to produce the dataset required for training the convolutional network. Subsequently, we combine DenseNet with existing clustering algorithms to improve the YOLOv4 algorithm to train the neural network for easier feature extraction. The trained neural network is then used to localize the target sound source and its pseudo-color map in the acoustic phase cloud map to obtain a pixel-level localization error. Finally, a standard chessboard grid is used to obtain the proportional relationship between the size of the acoustic phase cloud map and the actual physical space distance; then, the true lateral and longitudinal positioning error of sound imaging instrument can be obtained. Experimental results show that the mean average precision of the improved YOLOv4 algorithm in acoustic phase cloud map detection is 96.3%, the F1-score is 95.2%, and detection speed is up to 34.6 fps. The improved algorithm can rapidly and accurately determine the positioning error of sound imaging instrument, which can be used to analyze and evaluate the positioning performance of sound imaging instrument.

A case of multiple Vertebrobasilar artery fenestration misdiagnosed as vertebral artery dissection.

BACKGROUND: Fenestration of vertebra-basilar artery is an uncommon congenital vascular anomaly, which is identified by incidental findings on imaging in patients presented without related symptoms or in patients with intracerebral hemorrhage secondary to concomitant artery aneurysm or arteriovenous malformations. Yet, cases of fenestration being misdiagnosed as cerebral artery dissection have never been reported. CASE PRESENTATION: We present a patient of 66-year-old female with acute onset of dizziness after chiropractic manipulation of the neck. Neck computed tomography angiography (CTA) showed 'double lumen' sign and 'intimal flap' of the V1 segment of the vertebral artery, which led to the initial diagnosis of vertebral artery dissection (VAD). However, vertebral artery fenestration at V1 segment was eventually identified by multi-directional digital subtraction angiography (DSA). Interestingly, concomitant vertebral fenestration at V3 segment, basilar fenestration and basilar artery tip aneurysm was also revealed by DSA. CONCLUSION: The triple fenestration at vertebrobasilar artery with basilar tip artery aneurysm is extremely rare, and the fenestration at the V1 segment of vertebral artery was easily misdiagnosed as VAD due to the similar imaging morphology.

Applications of chitin and chitosan nanofibers in bone regenerative engineering.

Promoting bone regeneration and repairing defects are urgent and critical challenges in orthopedic clinical practice. Research on bone substitute biomaterials is essential for improving the treatment strategies for bone regeneration. Chitin and its derivative, chitosan, are among the most abundant natural biomaterials and widely found in the shells of crustaceans. Chitin and chitosan are non-toxic, antibacterial, biocompatible, degradable, and have attracted significant attention in bone substitute biomaterials. Chitin/chitosan nanofibers and nanostructured scaffolds have large surface area to volume ratios and high porosities. These scaffolds can be fabricated by electrospinning, thermally induced phase separation and self-assembly, and are widely used in biomedical applications such as biological scaffolds, drug delivery, bacterial inhibition, and wound dressing. Recently, some chitin/chitosan-based nanofibrous scaffolds have been found structurally similar to bone's extracellular matrix and can assist in bone regeneration. This review outlines the biomedical applications and biological properties of chitin/chitosan-based nanofibrous scaffolds in bone tissue engineering.

High CCL5 expression is associated with osteosarcoma metastasis and poor prognosis of patients with osteosarcoma.

Osteosarcoma is the most common primary malignant tumor of the skeletal system and is characterized by an aggressive clinical course and high metastatic potential. Regulated upon Activation Normal T cell Expressed and Secreted, also termed C­C motif chemokine ligand 5 (CCL5), is associated with metastasis and poor prognosis in various types of cancer. The aim of the current study was to investigate the association between CCL5 expression and clinicopathological features and prognosis in patients with osteosarcoma. Tissue microarrays and reverse transcription­quantitative polymerase chain reaction and immunohistochemistry were used to examine the expression of CCL5 in human osteosarcoma tissues. The prognostic value of CCL5 expression was evaluated by the Kaplan­Meier method and Cox proportional hazards regression model. The rate of high CCL5 expression was significantly higher in metastatic osteosarcomas than in osteosarcomas without metastases. The overall survival rates (P=0.001) and the metastasis­free survival rates (P<0.001) of the low CCL5 expression group were significantly higher than the CCL5 high expression group. Multivariate Cox regression analysis indicated that CCL5 expression had independent predictive value for the prognosis of patients with osteosarcoma. In conclusion, the data of the current study indicated that CCL5 may serve as a biomarker for prognosis of osteosarcoma, and may be a potential molecular target for osteosarcoma therapy.

Lentivirus-induced knockdown of LRP1 induces osteoarthritic-like effects and increases susceptibility to apoptosis in chondrocytes via the nuclear factor-κB pathway.

Low-density lipoprotein receptor-related protein 1 (LRP1) is known to regulate cell survival and inflammation. The present study investigated the involvement of LRP1 in the regulation of tumor necrosis factor (TNF)-α-induced expression of matrix metalloproteinase (MMP)-13. Furthermore, the study aimed to elucidate the mechanisms underlying the effects of LRP1 on TNF-α-induced inflammation and apoptosis of chondrocytes. Lentivirus-mediated RNA interference techniques were used to knockdown the LRP1 gene. Subsequently, the effects of LRP1 on TNF-α-induced MMP-13 expression were determined using quantitative polymerase chain reaction, western blot analysis and ELISA. Furthermore, the TNF-α-induced intracellular pathway was investigated using a nuclear factor (NF)-κB inhibitor (Bay 11-7082). In addition, the effect of LRP1 regulation on growth and apoptosis in chondrocytes was investigated using western blot analysis and a TUNEL assay. LRP1 knockdown was shown to increase TNF-α-induced MMP-13 expression via the activation of the NF-κB (p65) pathway, which reduced the expression of collagen type II and cell viability. In addition, LRP1 inhibited cell apoptosis by increasing the expression of phospho-Akt and B-cell lymphoma 2 (Bcl-2), while suppressing the expression of caspase-3 and Bcl-2-associated X protein. The results of the present study indicated that LRP1 was able to inhibit TNF-α-induced apoptosis and inflammation in chondrocytes. Therefore, LRP1 may be an effective osteoarthritis inhibitor, potentially providing a novel approach for antiarthritic therapeutics.

Gastrodin prevents steroid-induced osteonecrosis of the femoral head in rats by anti-apoptosis.

BACKGROUND: Gastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH. METHODS: All 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups. RESULTS: The incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower. CONCLUSION: Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.

The influence of a half-course tourniquet strategy on peri-operative blood loss and early functional recovery in primary total knee arthroplasty.

PURPOSE: The aim of this study was to explore the influence of a half-course tourniquet strategy on the peri-operative blood loss and early functional recovery in primary total knee arthroplasty. METHODS: A prospective clinical randomised controlled study was carried out in which 64 patients were equally divided into two groups: half-course group and whole-course group. A series of indicators were observed and recorded. These included operation time, peri-operative blood loss, visual analogue scale (VAS) score of the thigh or knee, limb swelling index, rehabilitation progress and occurrence of deep venous thrombosis cases. RESULTS: There was no significant difference in operation time between the two groups. The intra-operative blood loss was slightly more in the half-course group, while the difference was not significant. The post-operative blood loss and calculated blood loss were less in the half-course group and the difference was significant. The thigh VAS score, limb swelling and time intervals required for patients to achieve straight leg raises and 90° of knee flexion in the half-course group were better than in the whole-course group. No case of symptomatic deep venous thrombosis happened in this study, while occult incidence of deep venous thrombosis happened in both groups, but no significant difference between the groups was confirmed. CONCLUSIONS: The half-course tourniquet strategy could decrease the total peri-operative blood loss in primary total knee arthroplasty. It was beneficial in helping patients to achieve earlier functional recovery by improving the pain experience and limb swelling early in the post-operative period.