Activating Mitochondrial Sirtuin 3 in Chondrocytes Alleviates Aging-Induced Fibrocartilage Layer Degeneration and Promotes Healing of Degenerative Rotator Cuff Injury.

The present study aimed to examine the impact of mitochondrial sirtuin 3 (SIRT3) on the degenerative rotator cuff injury, which is a prevalent issue among the elderly population primarily due to aging-related tissue degradation. The study hypothesized that SIRT3, as a major deacetylase in mitochondria, is a significant factor in controlling the quality of mitochondria and the deterioration of fibrocartilage, a crucial component of the rotator cuff. Results showed that the aging process led to weakened biomechanical properties and degeneration of the fibrocartilage layer in mice, accompanied by a decrease in SIRT3 expression. SIRT3 activation ameliorated the aging-related disruption of chondrocyte phenotype and fibrocartilage degradation. SIRT3 activator honokiol improved the phenotype of senescent chondrocytes and promoted rotator cuff healing in aged mice through SIRT3 activation. In conclusion, the findings suggested that the decline in SIRT3 levels with age contributes to rotator cuff degeneration and chondrocyte senescence, and that SIRT3 activation through the use of honokiol is an effective approach for promoting rotator cuff healing in the elderly population.

Exosomes from CD133+ human urine-derived stem cells combined adhesive hydrogel facilitate rotator cuff healing by mediating bone marrow mesenchymal stem cells.

Background: The inadequate regeneration of natural tissue (mainly fibrocartilage) between tendon and bone during rotator cuff (RC) repair results in an unsatisfactory quality of RC healing. Cell-free therapy based on stem cell exosomes is a safer and more promising approach for tissue regeneration. Here, we investigated the effect of exosomes from human urine-derived stem cells (USCs) and their subpopulations (CD133+USCs) on RC healing. Methods: USCs were isolated from urine and sorted by flow cytometry to obtain CD133+ urine-derived stem cells (CD133+ USCs). Urine-derived stem cell exosomes (USC-Exos) and CD133+ urine-derived stem cell exosomes (CD133+ USC-Exos) were subsequently isolated from the cell supernatant and identified by transmission electron microscopy (TEM), particle size analysis, and Western blot. We performed in vitro functional assays to evaluate the effects of USC-Exos and CD133+ USC-Exos on human bone marrow mesenchymal stem cells (BMSCs) proliferation, migration, osteogenic differentiation, and chondrogenic differentiation. In vivo experiments were performed by local injection of exosome-hydrogel complexes for the treatment of RC injury. The effects of CD133+ USC-Exos and USC-Exos on RC healing were assessed from imaging, histological, and biomechanical tests. Results: CD133+ USCs were positive for CD29, CD44, CD73, CD90, CD133, but negative for CD34 and CD45. Differentiation ability test results showed that both USCs and CD133+ USCs had the potential for osteogenic, chondrogenic, and adipogenic differentiation, but CD133+ USCs had stronger chondrogenic differentiation ability. CD133+ USC-Exos and USC-Exos could be efficiently taken up by BMSCs and promote their migration, osteogenic and chondrogenic differentiation. However, CD133+ USC-Exos could promote the chondrogenic differentiation of BMSCs more than USC-Exos. Compared with USC-Exos, CD133+ USC-Exos could promote the healing of bone-tendon interface (BTI) more effectively, which might be related to its ability to promote the differentiation of BMSCs into chondroblasts. Although the two exosomes exhibited the same effect in promoting subchondral bone repair in BTI, the CD133+ USC-Exos group had higher histological scores and stronger biomechanical properties. Conclusion: CD133+ USC-Exos hydrogel complex may become a promising therapeutic approach for RC healing based on stem cell exosomes. The translational potential of this article: This is the first study to assess the specific role of CD133+ USC-Exos in RC healing which may be related to the activation of BMSCs by CD133+ USC-Exos towards chondrogenic differentiation. Further, our study provides a reference for possible future treatment of BTI by applying CD133+ USC-Exos hydrogel complex.

NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.

Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.

Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis.

INTRODUCTION: Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown. OBJECTIVES: This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. METHODS: Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hitmodel of MV afteracidaspiration-inducedlunginjuryin mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered. RESULTS: The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacologicalinhibitionorknockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent Ca2+ influx and ATP release in lung epithelial cells. CONCLUSIONS: Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novelstrategyfor the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis.

Negative regulator NLRC3: Its potential role and regulatory mechanism in immune response and immune-related diseases.

NLRC3 is a member of the pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) family, and plays a pivotal regulatory role in modulating the activation of immune cells. In macrophages, NLRC3 inhibits the activation of the NF-κB signaling pathway, the STING/TBK1 signaling pathway, and the formation of the inflammasome. In the context of T cells immune response, NLRC3 prevents the activation of T cells by regulating the function of dendritic cells and directly influencing the function of T cells. Different from other pattern recognition receptors, NLRC3 is more closely associated with regulatory activity than pathogens recognition, it influences the fates of cells, for example, prevents proliferation, promotes apoptosis and inhibits pyroptosis. These cellular functions regulated by NLRC3 are involved in the development processes of a variety of diseases, such as infectious disease, sterile inflammatory diseases, and cancer. However, its characteristics, function and regulatory mechanism in immune response and immune-related diseases have not been addressed fully. In this review, we elaborate the potential roles of NLRC3 from several different levels, include molecular mechanism, cellular functions in the immune-related diseases.

Mechanical stimulation improves rotator cuff tendon-bone healing via activating IL-4/JAK/STAT signaling pathway mediated macrophage M2 polarization.

Background: It is well known that appropriate mechanical stimulation benefits tendon-bone (T-B) healing, however, the mechanisms behind this are still uncovered completely. Here, we aimed to explore whether the IL-4/JAK/STAT signaling pathway mediated macrophage polarization was involved in mechanical stimulation induced T-B healing. Method: C57BL/6 mice rotator cuff (RC) repair model was established, and the mice were randomly allocated to the following group. 1. Mice were allowed for free cage activities after surgery (FC group); 2. Mice received treadmill running initiated on postoperative day 7 (TR group); 3. Mice only received a local injection of hydrogel containing IL-4 neutralizing antibody without postoperative intervention (FC â€‹+ â€‹AF-404-SP group); 4. Mice received a local injection of hydrogel containing IL-4 neutralizing antibody and postoperative treadmill running (TR â€‹+ â€‹AF-404-SP group). The expression of IL-4 within supraspinatus tendon (SST) enthesis was measured by Enzyme-linked immunosorbent assay (ELISA). In addition, the activation of JAK/STAT signaling pathway in macrophages and identification of macrophage phenotype at the RC insertion site was detected by Flow cytometry and qRT-PCR. T-B healing quality in this RC repair model was evaluated by histological staining, Micro-computed tomography (Micro-CT) scanning, and biomechanical testing. Result: In this study, using the RC repair model, we confirmed that generation of IL-4, activation of the JAK/STAT signaling pathway in macrophages, the ability of macrophages to polarize towards M2 subtype, and T-B healing quality were significantly enhanced in TR group compared to FC group. When comparing FC â€‹+ â€‹AF-404-SP group with TR â€‹+ â€‹AF-404-SP group, it was found that the mechanical stimulation induced this effect was depleted following the blockade of the IL-4/JAK/STAT signaling pathway. Conclusion: Our finding suggested that mechanical stimulation could accelerate T-B healing via activating the IL-4/JAK/STAT signaling pathway that modulates macrophages to polarize towards M2 subtype. The translational potential of this article: This is the first study to reveal a significant role of mechanical stimulation in the IL-4/JAK/STAT signaling pathway activation and macrophage polarization during RC T-B healing, which highlights the IL-4/JAK/STAT signaling pathway as a potential target to mediate macrophage M2 polarization and improves T-B healing for RC repair.

[Research advances of myeloid-derived suppressor cells in sepsis-induced immunosuppression].

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Most patients with sepsis underwent a state of immune suppression after surviving the acute inflammatory response, and were susceptible to secondary nosocomial infections, leading to a prolonged hospitalization and increased mortality rate. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population with immunosuppressive activities, can contribute to the development of immunosuppression in patients with cancer and inhibit the host immune response, but the characteristics of MDSCs and their functional mechanism has not been fully addressed in the development of sepsis-induced immunosuppression. Thus, this review will summary the new findings on the mechanisms of MDSCs in septic immunosuppressionin order to provide ideas and directions for targeting MDSCs as treatment of septic immunosuppression.

Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study.

Intensive care unit (ICU)-acquired infection is a common cause of poor prognosis of sepsis in the ICU. However, sepsis-associated ICU-acquired infections have not been fully characterized. The study aims to assess the risk factors and develop a model that predicts the risk of ICU-acquired infections in patients with sepsis. Methods: We retrieved data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. A multivariable logistic regression model was used to identify independent risk factors that could predict ICU-acquired infection. We also assessed its discrimination and calibration abilities and compared them with classical score systems. Results: Of 16,808 included septic patients, 2,871 (17.1%) developed ICU-acquired infection. These patients with ICU-acquired infection had a 17.7% ICU mortality and 31.8% in-hospital mortality and showed a continued rise in mortality from 28 to 100 days after ICU admission. The classical Systemic Inflammatory Response Syndrome Score (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Charlson Comorbidity Index (CCI), and Acute Physiology Score III (APS III) scores were associated with ICU-acquired infection, and cerebrovascular insufficiency, Gram-negative bacteria, surgical ICU, tracheostomy, central venous catheter, urinary catheter, mechanical ventilation, red blood cell (RBC) transfusion, LODS score and anticoagulant therapy were independent predictors of developing ICU-acquired infection in septic patients. The nomogram on the basis of these independent predictors showed good calibration and discrimination in both the derivation (AUROC = 0.737; 95% CI, 0.725-0.749) and validation (AUROC = 0.751; 95% CI, 0.734-0.769) populations and was superior to that of SIRS, SOFA, OASIS, SAPS II, LODS, CCI, and APS III models. Conclusions: ICU-acquired infections increase the likelihood of septic mortality. The individualized prognostic model on the basis of the nomogram could accurately predict ICU-acquired infection and optimize management or tailored therapy.

Treatment of chronic lateral ankle instability by double-band anatomical reconstruction of the anterior talofibular ligament's fibular enthesis. / è·è “å‰éŸ§å¸¦è “éª¨æ­¢ç‚¹åŒæŸè§£å‰–é‡å»ºæ²»ç–—æ ¢æ€§è¸å ³èŠ‚å¤–ä¾§ä¸ç¨³.

OBJECTIVES: Anterior talofibular ligament (ATFL) injury is one of the most common injuries in sports medicine, resulting in chronic lateral ankle instability (CLAI). The patients' daily life may be seriously affected by ankle osteoarthritis and other irreversible damages, if the ATFL injury is not treated in time and drags on. Patients with ATFL injury who show no significant recovery after 3-6 months of conservative treatment should consider surgical treatment as soon as possible to restore ankle stability and function. This study aims to investigate the effect of double-bands anatomical reconstruction of the ATFL's fibular enthesis for the treatment of CLAI. METHODS: A retrospective review was conducted on 67 patients diagnosed with CLAI in the Department of Sports Medicine, Xiangya Hospital, Central South University from January 2015 to January 2018, including 42 males and 25 females, aged from 17 to 41 years old, with disease course of (12.6±3.2) months. Of the 67 patients, 29 left ankles and 38 right ankles were included in this study. Patients suffered from repeated sprains which leaded to pain, swelling and obvious ankle relaxation. There were obvious tenderness at the ATFL insertion and the calcaneal fibular ligament insertion. Both the anterior ankle drawer test and the varus stress test were positive. Other ankle disorders were excluded by X-ray. Preoperative color Doppler ultrasonography and magnetic resonance examination were performed to observe ATFL injury. All the patients had surgical indications and no obvious contraindications, and they were treated with arthroscopic debridement and double-bundle anatomical reconstruction of the AFTL's fibular enthesis under anesthesia. Postoperative routine nursing and standardized rehabilitation exercise were recommended. Outpatient follow-up was conducted at 3, 6, 12, and 24 months postoperatively. American Orthopaedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Functional (KAF) score, and the Japanese Society for Surgery of the Foot (JSSF) scale were used to evaluate the clinical outcomes. RESULTS: Intraoperative arthroscopic examination of 67 patients showed inflammatory synovial hyperplasia in 52 cases (77.6%), obvious osteophyte hyperplasia in 12 cases (17.9%), talus osteochondral injury of grade II-III in 23 cases (34.3%), and cartilage injury of grade IV in 5 cases (7.5%). All operations were carried out successfully, and both the anterior ankle drawer test and the varus stress test were negative under anesthesia after surgery. The anchors were in good position. Among them, 3 patients (4.5%) got temporary superficial peroneal nerve palsy and skin numbness at ankle joint after surgery, which gradually recovered within 2 weeks. There were no serious perioperative complications such as infection and suppurative arthritis. Postoperative follow-up was conducted for 12-24 (15.64±3.17) months. At the last follow-up, all patients were walking normally. Most patients had no pain or occasionally mild pain. Ankle function and motion were restored without re-instability. Sixty-four patients (95.5%) worked and exercised as before the surgery. Standing X-ray examination indicated normal joint space without stenosis, and the internal fixation was in good position. Postoperative AOFAS scores (94.78±6.37) were significantly better than the preoperative scores (64.17±12.43, P<0.01). Besides, the KAF scores and the JSSF ankle/hindfoot scale before surgery were significantly increased (KAF: 91.04±11.36 vs 59.74±13.63, P<0.01; JSSF: 95.32±10.21 vs 66.92±14.38, P<0.01). CONCLUSIONS: Arthroscopic debridement and double-bands anatomical reconstruction of the ATFL's fibular enthesis for the treatment of CLAI gains beneficial short-term effects for its minimal invasion and quick recovery.

Efficacy and safety of a novel personalized navigation template in proximal femoral corrective osteotomy for the treatment of DDH.

BACKGROUND: This present study is aimed to retrospectively evaluate the efficacy and safety of a novel personalized navigation template in proximal femoral corrective osteotomy for the treatment of DDH. METHODS: Twenty-nine consecutive patients with DDH who underwent proximal femoral corrective osteotomy were evaluated between August 2013 and June 2017. Based on the different surgical methods, they were divided into the conventional group (n = 14) and navigation template group (n = 15). The osteotomy degrees, radiation exposure, and operation time were compared between the two groups. RESULTS: No major complications relating to osteotomy surgery such as redislocation or avascular necrosis occurred in the navigation template group, which had more accurate osteotomy degrees, less radiation exposure, and shorter operation time when compared with the conventional group (P < 0.05). Moreover, there was significant difference according to the McKay criteria between the two groups (P = 0.0362). CONCLUSIONS: The novel personalized navigation template in proximal femoral corrective osteotomy is effective and safe, which could improve the femoral osteotomy accuracy, reduce radiation exposure, and shorten operation time.

Behavioural Patterns and Postnatal Development in Pups of the Asian Parti-Coloured Bat, Vespertilio sinensis.

Behavioural development is an important aspect of research on animal behaviour. In bats, many studies have been conducted on the development of flight behaviour, but the postnatal behavioural development of bats remains largely unexplored. We studied the behaviours and postnatal development of infant bats by conducting controlled video recorded experiments. Our results showed that before weaning, Asian parti-coloured bats (Vespertilio sinensis) were able to exhibit four types of behaviours, namely, crawling, head moving, wing flapping, and wing spreading, and these behaviours are different from those observed in experiments with adult bats. The number of occurrences of these behaviours was correlated with age and scaled mass index. Furthermore, the number of occurrences of these behaviours in young bats could also reflect their physical developmental status. In young bats, wing flapping and spreading might be a type of play behaviour. These behaviours were negatively correlated with the time of the first flight, indicating that they might help to promote individual physical development. Our results provide fundamental data for revealing the ontogenetic and neurophysiological mechanisms of behavioural development in bats.

In vitro compressive properties of skeletal muscles and inverse finite element analysis: Comparison of human versus animals.

Virtual finite element human body models have been widely used in biomedical engineering, traffic safety injury analysis, etc. Soft tissue modeling like skeletal muscle accounts for a large portion of a human body model establishment, and its modeling method is not enough explored. The present study aims to investigate the compressive properties of skeletal muscles due to different species, loading rates and fiber orientations, in order to obtain available parameters of specific material laws as references for building or improving the human body model concerning both modeling accuracy and computational cost. A series of compressive experiments of skeletal muscles were implemented for human gastrocnemius muscle, bovine and porcine hind leg muscle. To avoid long-time preservation effects, all experimental tests were carried out in 24 h after that the samples were harvested. Considering computational cost and generally used in the previous human body models, one-order hyperelastic Ogden model and three-term simplified viscoelastic quasi-linear viscoelastic (QLV) were selected for numerical analysis. Inverse finite element analysis was employed to obtain corresponding material parameters. With good fitting records, the simulation results presented available material parameters for human body model establishment, and also indicated significant differences of muscle compressive properties due to species, loading rates and fiber orientations. When considering one-order Ogden law, it is worthy of noting that the inversed material parameters of the porcine muscles are similar to those of the human gastrocnemius regardless of fiber orientations. In conclusion, the obtained material parameters in the present study can be references for global human body and body segment modeling.

Changes in the gut microbiota during Asian particolored bat (Vespertilio sinensis) development.

BACKGROUND: The gut microbiota is closely linked to host development, diet and health and is influenced by both the host and the environment. Although many studies have focused on the dynamics of the gut microbiota during development in captive animals, few studies have focused on the dynamics of the gut microbiota during development in wild animals, especially for the order Chiroptera. METHODS: In this study, we characterized the gut microbiota of the wild Asian particolored bat (Vespertilio sinensis) from 1 day to 6 weeks after birth. We explored the changes in their gut microbial community compositions, examined possible influencing factors, and predicted the feeding transition period. RESULTS: The gut microbiota changed during the development of V. sinensis. The alpha diversity of the bats' gut microbiota gradually increased but did not change significantly from the 1st day to the 4th week after birth; however, the alpha diversity decreased significantly in week 5, then stabilized. The beta diversity differed slightly in weeks 4-6. In week 4, the fecal samples showed the highest diversity in bacterial community composition. Thus, we predicted that the potential feeding transition period for V. sinensis may occur during week 4. Redundancy analysis showed that age and body mass index significantly affected the compositional changes of the gut microbiota in Asian particolored bats. CONCLUSION: The gut microbiota changed during the development of V. sinensis. We suggest that changes in the alpha and beta diversity during week 4 after birth indicate a potential feeding transition, highlighting the importance of diet in the gut microbiota during the development of V. sinensis.

Curcumin ameliorates monosodium urate-induced gouty arthritis through Nod-like receptor 3 inflammasome mediation via inhibiting nuclear factor-kappa B signaling.

BACKGROUND: Monosodium urate (MSU) crystals-induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti-inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive. METHODS: We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals-stimulated cells were collected and subjected to enzyme-linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod-like receptor 3 (NLRP3) inflammasome/nuclear factor-kappa B (NF-κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU-induced gouty arthritis rat models. RESULTS: Curcumin could reduce MSU crystals-induced IL-1ß and TNF-α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase-1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU-induced NF-κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU-induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL-1ß, TNF-α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase-1, caspase-1, pro-IL-1ß, and IL-1ß were downregulated by curcumin in vivo. CONCLUSIONS: These results indicated that curcumin could effectively ameliorate MSU crystal-induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF-κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis.

Anatomic reconstruction of anterior talofibular ligament with tibial tuberosity-patellar tendon autograft for chronic lateral ankle instability.

INTRODUCTION: Anatomic repair of the anterior talofibular ligament (ATFL) is challenging when the local ligamentous tissue is severely attenuated. Anatomic reconstruction of the ATFL with tibial tuberosity-patellar tendon (TT-PT) autograft is a feasible choice that can avoid the complicated tendon-bone healing and restore ankle stability. MATERIALS AND METHODS: From 2009 to 2015, 31 chronic lateral ankle instability (CLAI) patients (31 ankles), who had a serious injury on the ATFL only, were treated with anatomic reconstruction of ATFL with TT-PT. American orthopedic foot and ankle society ankle-hindfoot score (AHS), visual analog scale for pain score (VAS), Karlsson-Peterson score, Tegner activity level, and objective examination comprehending range of motion were used to evaluate the clinical outcomes before and after operation. Radiographically, talar tilt angles and anterior drawer were assessed in pre- and postoperative ankle stress views. RESULTS: Among the 31 ankles, 17 ankles with single-bundle ATFL and 14 ankles with double-bundle ATFL were found at operation. At a mean follow-up of 42 months (24-82 months), all patients were satisfied with the procedure. Mean AHS significantly increased from 60.5 ± 8.2 to 93.5 ± 4.8. Mean Karlsson-Peterson score significantly increased from 55.2 ± 11.0 preoperatively to 91.2 ± 6.9 at final follow-up. Average VAS significantly decreased from 5.9 ± 1.6 preoperatively to 1.4 ± 1.0 at the latest follow-up. Mean Tegner activity level was 3.7 ± 0.9 before operation, compared with 7.0 ± 0.8 after operation. On stress radiographs, mean talar tilt angle was 17.0 ± 3.4° before operation and 3.8 ± 2.1° at the latest follow-up. In addition, mean anterior tibiotalar translation was 7.5 ± 2.2 mm before operation and 1.8 ± 1.1 mm at the latest follow-up. CONCLUSION: Anatomic reconstruction of the ATFL using a TT-PT autograft allows bone-bone healing in talus and tendon-tendon/periosteum healing in fibula rather than requiring tendon-bone healing, which is an alternative choice for treating CLAI caused by single ATFL insufficiency.

A new hypothesis on the mechanism of atrophic non-union.

Non-union after bone fracture is rather common with an increasing frequency of incidence rate due to poorly treated early operations, among which the mechanism of atrophic non-union remains unclear. Previous opinions showed that impaired blood supply of affected limbs might mostly contribute to the atrophic non-union, which discriminated it with hypertrophic non-union. Nevertheless, there had been increasingly adequate evidences supporting that normal blood supplies existed in atrophic non-unions, as well as in hypertrophic non-unions or healthy bone fractures. Our hypothesis, based on the newly acquired evidences of atrophic non-union, was that there existed mesenchymal stem cells in the area of atrophic non-union. These mesenchymal stem cells, which remained temporally quiescent, could perform re-ossification under certain growth conditions, such as pressure during callus distraction with external fixator. According to the hypothesis, treatment for atrophic non-union should focus on the stimulation and reactivation of endogenetic mesenchymal stem cells or transplantation of autologous normal mesenchymal stem cells. This hypothesis may shed some light on the mechanism of atrophic non-union.

[Pharmacokinetics and tissue distribution of Schisandra chinensis extract in mice].

OBJECTIVE: To investigate the pharmacokinetics and tissue distribution of Schisandra chinensis in mice. METHODS: Schisandrin in mice plasma and tissues including heart, liver, spleen, lung and kidney was quantitatively determined by HPLC. RESULTS: The concentration-time curve of Schisandra chinensis extract was described by a single compartment model, Cmax was (2.17 +/- 0.27) mg/ mL, t(max) was (1.00 +/- 0.32) h, AUC0-->infinity, was (4.07 +/- 0.62) mg x h/mL. The sequence of distribution of schisandrin in mice body was as follows: liver > plasma > kidney > lung > heart > spleen. CONCLUSION: The distribution of extract in the body is abroad. Liver has relative high concentration of schisandrin, which is beneficial to the treatment of hepatic disease.