Expression analysis of microRNAs and mRNAs in myofibroblast differentiation of lung resident mesenchymal stem cells.

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease that involved the myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs). However, the specific molecular mechanisms of myofibroblast differentiation of LR-MSCs still remain a mystery. In this study, a comprehensive analysis of miRNAs and mRNAs changes in LR-MSCs treated with TGF-ß1 was performed. Through computational approaches, the pivotal roles of differentially expressed miRNAs that were associated with tight junction, pathways in cancer, focal adhesion, and cytokine-cytokine receptor interaction were shown. Kruppel-like factor 4 (Klf4) and inhibitor of growth family, member 5 (Ing5) may be the targets for the therapy of pulmonary fibrosis by inhibiting myofibroblast differentiation of LR-MSCs and EMT. Collectively, a molecular paradigm for understanding myofibroblast differentiation of LR-MSCs in IPF was provided by the integrated miRNA/mRNA analyses.

The Shh/Gli signaling cascade regulates myofibroblastic activation of lung-resident mesenchymal stem cells via the modulation of Wnt10a expression during pulmonary fibrogenesis.

Lung-resident mesenchymal stem cells (LR-MSCs) are important regulators of lung repair and regeneration, and evidence suggests that this cell population also plays a vital role in fibrosis. Crosstalk between sonic hedgehog (Shh) signaling and wingless/integrated (Wnt) has been demonstrated in idiopathic pulmonary fibrosis (IPF). However, the underlying correlation between LR-MSCs and the Shh-Wnt signaling cascade remains poorly understood. Here, we identified Wnt10a as a key factor in pulmonary fibrosis. Using a bleomycin mouse model, we found that highly expressed Wnt10a was secreted by LR-MSCs undergoing myofibroblastic differentiation. LR-MSCs with myofibroblast characteristics isolated from fibrotic lungs exhibited increased Shh pathway activity, suggesting their role as Shh targets. In vitro, LR-MSCs responded to stimulation by recombinant Shh, acquiring a myofibroblast phenotype. We further demonstrated that the Shh/glioblastoma (Gli) system machinery regulated LR-MSC-to-myofibroblast transition and pulmonary fibrosis via manipulation of Wnt/ß-catenin signaling. Accordingly, inhibition of the Shh-Wnt signaling cascade prevented LR-MSC transformation into myofibroblasts and ameliorated pulmonary fibrotic lesions. Moreover, induction of Wnt10a expression and activation of Shh/Gli signaling were confirmed in human pulmonary fibrosis. In summary, this study linking the Shh-Wnt signaling cascade with LR-MSC fibrogenic activity furthered the current understanding of pulmonary fibrosis pathogenesis and might provide a new perspective in the development of treatment strategies for IPF.

TNF-α-induced NF-κB activation promotes myofibroblast differentiation of LR-MSCs and exacerbates bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR-MSCs) and tumor necrosis factor-α (TNF-α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR-MSCs and TNF-α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro-inflammatory cytokine TNF-α and the transcription factor nuclear factor kappa B (NF-κB) p65 subunit were both upregulated in bleomycin-induced fibrotic lung tissue. In addition, we discovered that TNF-α promotes myofibroblast differentiation of LR-MSCs through activating NF-κB signaling. Interestingly, we also found that TNF-α promotes the expression of ß-catenin. Moreover, we demonstrated that suppression of the NF-κB signaling could attenuate myofibroblast differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis which were accompanied with decreased expression of ß-catenin. Our data implicates that inhibition of the NF-κB signaling pathway may provide a therapeutic strategy for pulmonary fibrosis, a disease that warrants more effective treatment approaches.

M2 macrophages promote myofibroblast differentiation of LR-MSCs and are associated with pulmonary fibrogenesis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the histopathological pattern of usual interstitial pneumonia and is associated with a high mortality rate. Recently, lung resident mesenchymal stem cells (LR-MSCs) have been identified as an important contributor to myofibroblast activation in pulmonary fibrosis. Macrophages are also believed to play a critical role in pulmonary fibrosis. However, the underlying connections between LR-MSCs and macrophages in the pathogenesis of pulmonary fibrosis are still elusive. METHODS: In this study, we investigated the interaction between LR-MSCs and macrophages using a bleomycin-induced mouse pulmonary fibrosis model and a coculture system. RESULTS: Here, we show that blocking pulmonary macrophage infiltration attenuated bleomycin-induced pulmonary fibrosis. In addition, as determined by flow cytometry, we discovered that the recruited macrophages in fibrotic lungs of bleomycin-treated mice were mainly M2 macrophages. In particular, we found that M2, rather than M1 macrophages, promoted myofibroblast differentiation of LR-MSCs. Moreover, we demonstrated that suppression of the Wnt/ß-catenin signaling pathway could attenuate myofibroblast differentiation of LR-MSCs induced by M2 macrophages and bleomycin-induced pulmonary fibrosis. Tissue samples from IPF patients confirmed the infiltration of M2 macrophages and activation of Wnt/ß-catenin signaling pathway. CONCLUSION: In summary, this study furthered our understanding of the pulmonary fibrosis pathogenesis and highlighted M2 macrophages as a critical target for treating pulmonary fibrosis.

Effect of Tendon Stem Cells in Chitosan/ß-Glycerophosphate/Collagen Hydrogel on Achilles Tendon Healing in a Rat Model.

BACKGROUND The aim of this study was to determine whether the local application of tendon stem cells (TSCs) with chitosan/ß-glycerophosphate/collagen(C/GP/Co) hydrogel promotes healing after an acute Achilles tendon injury in a rat model. MATERIAL AND METHODS Ninety-six Sprague-Dawley (SD) rats were used to make an Achilles tendon defect model, then the animals were randomly divided into 4 groups consisting of 8 rats each: control group, hydrogel group, TSCs group, and TSCs with hydrogel group. At 2, 4, and 6 weeks after treatment, tendon samples were harvested, and the quality of tendon repair was evaluated based on histology, immunohistochemistry, and biomechanical properties. RESULTS Combining TSCs with C/GP/Co hydrogel significantly enhances tendon healing compared with the control, hydrogel, and TSCs groups. The improved healing was indicated by the improvement in histological and immunohistochemistry outcomes and the increase in the biomechanical properties of the regenerated tissue at both 4 and 6 weeks post-injury. CONCLUSIONS This study demonstrates that the transplantation of TSCs combined with C/GP/Co hydrogel significantly improved the histological, immunohistochemistry, and biomechanical outcomes of the regenerated tissue at 4 and 6 weeks after implantation. TSCs with C/GP/Co hydrogel is a potentially effective treatment for tendon injury.

Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process.

In this study, we determined the effects of transforming growth factor-beta (TGF-ß) and Wnt/ß-catenin signaling on myofibroblast differentiation of NIH/3T3 fibroblasts in vitro and evaluated the therapeutic efficacy of NSC668036 in bleomycin-induced pulmonary fibrosis murine model. In vitro study, NSC668036, a small organic inhibitor of the PDZ domain in Dvl, suppressed ß-catenin-driven gene transcription and abolished TGF-ß1-induced migration, expression of collagen I and α-smooth muscle actin (α-SMA) in fibroblasts. In vivo study, we found that NSC668036 significantly suppressed accumulation of collagen I, α-SMA, and TGF-ß1 but increased the expression of CK19, Occludin and E-cadherin that can inhibit pulmonary fibrogenesis. Because fibrotic lung exhibit aberrant activation of Wnt/ß-catenin signaling, these data collectively suggest that inhibition of Wnt/ß-catenin signaling at the Dvl level may be an effective approach to the treatment of fibrotic lung diseases.

Medial displacement calcaneal osteotomy with posterior tibial tendon reconstruction for the flexible flatfoot with symptomatic accessory navicular.

We investigated the clinical outcomes after medial displacement calcaneal osteotomy with reconstruction of the posterior tibial tendon insertion on the navicular, in patients with flexible flatfoot with accessory navicular symptoms. From December 2008 to July 2011, 16 patients (21 feet) with a flexible flatfoot, symptomatic accessory navicular, and obvious heel valgus underwent medial displacement calcaneal osteotomy and reconstruction with posterior tibial tendon insertion on the navicular bone. The patients were evaluated preoperatively, 6 weeks and 3, 6, and 12 months postoperatively, and every 6 months thereafter. The clinical examination was undertaken using the American Orthopaedic Foot and Ankle Society ankle and midfoot scores. The radiologic assessments included the arch height, calcaneus inclination angle, talocalcaneal angle, and talar first metatarsal angle on the lateral weightbearing radiograph. The talocalcaneal angle and talar first metatarsal angle was assessed on the anteroposterior view of the weightbearing foot. Heel valgus alignment was assessed on the axial hindfoot radiographs. The mean follow-up duration was 28.5 months (range 18 to 48). All patients were satisfied with the clinical results and were pain free 6 months postoperatively. No cases of wound infection or nerve injury developed. The mean American Orthopaedic Foot and Ankle Society score improved from 53.3 ± 6.5 to 90.8 ± 1.4 at the last follow-up visit (p < .01). The improvements in all radiographic parameters were statistically significant between the preoperative and last follow-up examinations (p < .01). The heel valgus of all patients was corrected. Our results have shown that medial displacement calcaneal osteotomy with reconstruction of the posterior tibial tendon insertion on the navicular bone is an effective treatment of flexible flatfoot with symptomatic accessory navicular, associated with excellent clinical outcomes and correction of the deformity.

Biomimetic Chiral Nanomaterials with Selective Catalysis Activity.

Chiral nanomaterials with unique chiral configurations and biocompatible ligands have been booming over the past decade for their interesting chiroptical effect, unique catalytical activity, and related bioapplications. The catalytic activity and selectivity of chiral nanomaterials have emerged as important topics, that can be potentially controlled and optimized by the rational biochemical design of nanomaterials. In this review, chiral nanomaterials synthesis, composition, and catalytic performances of different biohybrid chiral nanomaterials are discussed. The construction of chiral nanomaterials with multiscale chiral geometries along with the underlying principles for enhancing chiroptical responses are highlighted. Various biochemical approaches to regulate the selectivity and catalytic activity of chiral nanomaterials for biocatalysis are also summarized. Furthermore, attention is paid to specific chiral ligands, materials compositions, structure characteristics, and so on for introducing selective catalytic activities of representative chiral nanomaterials, with emphasis on substrates including small molecules, biological macromolecule, and in-site catalysis in living systems. Promising progress has also been emphasized in chiral nanomaterials featuring structural versatility and improved chiral responses that gave rise to unprecedented chances to utilize light for biocatalytic applications. In summary, the challenges, future trends, and prospects associated with chiral nanomaterials for catalysis are comprehensively proposed.

Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families. METHODS: Clinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio-based whole-exome sequencing. Pyrosequencing, chip-based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants. RESULTS: Novel heterozygous variants in SMC3 were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G>A) in SMC3. The mutated allele G>A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in vitro minigene splicing analysis validated that the c.2535+1G>A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C>A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies. CONCLUSION: Both patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified SMC3 gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.

Peri-navicular arthrodesis for the Stage III Müller-Weiss disease.

BACKGROUND: We aimed to report our results of peri-navicular arthrodesis with autologous iliac bone graft for Stage III Müller-Weiss disease. METHODS: Nine cases of Stage III Müller-Weiss disease according to the Maceira classification (four male and five female) with average age of 48.2 (range, 41 to 58) years, had mild or severe midfoot pain with the longitudinal arch collapse. The patients, all of whom had failed conservative treatment for more than 6 months, underwent peri-navicular arthrodesis. All patients were followed up at 3, 6, 9, and 12 months, and then every 6 months with AOFAS ankle-hindfoot scores and radiographic measurements. Mean followup time for radiological and clinical evaluation was 22.4 (rangem 12 to 52) months. RESULTS: All patients were satisfied with their clinical results without pain 12 months after surgery. The mean AOFAS ankle-hindfoot scores improved from 40.1±8.3 preoperatively to 90.9±2.1 at the last followup (p<0.05). A solid fusion was found in all cases at 3 months after surgery by radiographic and clinical evaluation. The average longitudinal arch height increased from 46.1±2.1 mm preoperatively to 53.5±2.3 mm at the last followup (p<0.05) on the lateral weightbearing radiograph. CONCLUSION: The peri-navicular arthrodesis with autologous iliac bone graft resulted in a good outcome for Stage III Müller-Weiss disease with good clinical outcomes, high fusion rate, and obvious improvement of the longitudinal arch height.

[Effects of different cyclic mechanical stretching loads on human tenocytic cytoskeleton in vitro].

OBJECTIVE: To investigate the human tenocyte cytoskeleton under different in vitro stretching conditions and analyze the relations between the changes of tenocytic cytoskeleton and different stretching loads. METHODS: Human tenocytes, cultivated for 5 -7 passages, were stretched under 4%, 8% and 12% cyclic mechanical stretching with a duration of 2, 4, 8, 12, 24 hours and a frequency of 0.5 and 1.0 Hz. Laser scanning confocal microscope was used to examine the changes of F-actin and nucleus after immunofluorescent staining at different cyclic mechanical stretching loads on human tenocyte. The uni-cell average fluorescence intensity was measured with an image analysis system by the photos of human tenocyte cytoskeleton and analyzed by the single factor analysis of variance. RESULTS: After cyclic stretching under 4% stretching with a duration of 2 hours at 0.5 Hz, the microfilament of human tenocyte had an irregular and dim alignment. F-actin was thicker and ruptured under 4% stretching with a duration of 4 hours. Under 8% stretching with a duration of 4 hours at 0.5 Hz, all actin microfilaments ruptured, but part of membrane microfilament remained intact. There was a rising trend of actin filament fracturing under 12% stretching with a duration of 2, 4, 8, 12, 24 hours at 1.0 Hz. And all actin filaments fractured at 24 hours. In the control group, the fluorescent intensity of F-actin was at the highest and the filament remained intact. Under the same stretching frequency, the fluorescent intensity of F-actin had a declining trend and significant differences existed under different stretching loads with different durations (P < 0.05). The fluorescent intensity of F-actin increased in all experimental groups, but it was lower than that of the control group with a duration of 8 hours. The expression of F-actin decreased with a longer duration and reached its lowest at 24 hours. The most obvious phenomenon of nuclear condensation and apoptotic body formation was observed under 4% stretching with a duration of 4 hours at 0.5 Hz. CONCLUSION: Different cyclic mechanical stretching may cause the in vitro breakage and depolymerization of human tenocytic F-actin. Such an effect correlates with stretching force and its duration.

Alveolar epithelial cell-derived Sonic hedgehog promotes pulmonary fibrosis through OPN-dependent alternative macrophage activation.

The alternative activation of macrophages in the lungs has been considered as a major factor promoting pulmonary fibrogenesis; however, the mechanisms underlying this phenomenon are still elusive. In this study, we investigated the interaction between macrophages and fibrosis-associated alveolar epithelial cells using a bleomycin-induced mouse pulmonary fibrosis model and a coculture system. We demonstrated that fibrosis-promoting macrophages are spatially proximate to alveolar type II (ATII) cells, permissive for paracrine-induced macrophage polarization. Importantly, we revealed that fibrosis-associated ATII cells secrete Sonic hedgehog (Shh), a hedgehog pathway ligand, and that ATII cell-derived Shh promotes the development of pulmonary fibrosis by osteopontin (OPN)-mediated macrophage alternative activation. Mechanistically, Shh promotes the secretion of OPN in macrophages via Shh/Gli signaling cascade. The secreted OPN acts on the surrounding macrophages in an autocrine or paracrine manner and induces macrophage alternative activation through activating the JAK2/STAT3 signaling pathway. Tissue samples from idiopathic pulmonary fibrosis patients confirmed the increased expression of Shh and OPN in ATII cells and macrophages, respectively. Together, our study illustrated an alveolar epithelium-dependent mechanism for macrophage M2 polarization and pulmonary fibrogenesis and suggested that targeting Shh may offer a selective and efficient therapeutic strategy for the development and progression of pulmonary fibrosis.

[Measurement of humeral head retroversion angle with multislice spiral computerized tomography volume rendering technique].

OBJECTIVE: To verify the accuracy of measurement of humeral head retroversion angle with multislice spiral computerized tomography (MSCT) volume rendering technique. METHODS: Twenty cadaveric humeri, 9 left and 11 right, free from traumatic or degenerative disfigurement, were harvested from embalmed cadavers. Before all soft tissues were removed by sharp dissection these humeri were scanned with 16 slice spiral CT scanner (CT1 group); then underwent anatomical measurement (anatomical measuring group); and at last, these humeri with marked anatomic neck were scanned with 16 slice spiral CT scanner again (CT2 group). The measurement was done by 2 orthopedists independently so as to diminish the measuring error. The differences in the humeral head retroversion angle between the CT1 group and anatomical measuring group, and the CT2 group and anatomical measuring group were analyzed with paired-samples T test. RESULTS: It showed that the results have no significant difference among them. The difference in the average value of humeral head retroversion angle between the CT1 group and anatomical measuring group was 1.64 degrees, and that between the CT2 group and anatomical measuring group was 0.65 degrees. CONCLUSION: Simple, fast, and precise, and suitable for clinical application, MSCT volume rendering technique can be used preoperatively, thus helping to realize the idea of individualization of shoulder arthroplasty and shoulder prosthesis. Although this technique is easy to be influence by the subjective factors of the observers, increase of experience and rational measurement may minimize the measurement error.

The hedgehog and Wnt/ß-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Resident mesenchymal stem cells (LR-MSCs) can undergo phenotype conversion to myofibroblasts to augment extracellular matrix production, impairing function and contributing to pulmonary fibrosis. Hedgehog and Wnt signaling are developmental signal cascades that play an essential role in regulating embryogenesis and tissue homeostasis. Recently, it has been reported that both hedgehog and Wnt signaling play important roles in pulmonary fibrogenesis. Thus, the identification of specific target regulators may yield new strategy for pulmonary fibrosis therapies. In our work, we demonstrated the critical role of Gli1, Wnt7b, Wnt10a and Fzd10 in the process of pulmonary fibrogenesis in vitro and in vivo. Gli1 was induced in LR-MSCs following TGF-ß1 treatment and fibrotic lung tissues. Inhibition of Gli1 suppressed myofibroblast differentiation of LR-MSCs and pulmonary fibrosis, and decreased the expression of Wnt7b, Wnt10a and ß-catenin. Gli1 bound to and increased promoter activity of the Wnt7b and Wnt10a genes, and Wnt7b and Wnt10a were critical activators of Wnt/ß-catenin signaling. It was noteworthy that Fzd10 knockdown reduced Wnt7b and Wnt10a-induced activation of Wnt/ß-catenin signaling, which imply that Wnt7b and Wnt10a may be the ligands for Fzd10. Moreover, siRNA-mediated inhibition of Fzd10 prevented TGF-ß1-induced myofibroblast differentiation of LR-MSCs in vitro and impaired bleomycin-induced pulmonary fibrosis. We conclude that hedgehog and Wnt/ß-catenin signaling play a critical role in promoting myofibroblast differentiation of LR-MSCs and development of pulmonary fibrosis. These findings elucidate a therapeutic approach to attenuate pulmonary fibrosis through targeted inhibition of Gli1 or Fzd10.

Inhibition of Wnt/ß-catenin signaling suppresses myofibroblast differentiation of lung resident mesenchymal stem cells and pulmonary fibrosis.

An emerging paradigm proposes a crucial role for lung resident mesenchymal stem cells (LR-MSCs) via a fibroblastic transdifferentiation event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Aberrant activation of Wnt/ß-catenin signaling occurs in virtually all fibrotic lung diseases and is relevant to the differentiation of mesenchymal stem cells (MSCs). In vitro, by measuring the protein levels of several key components involved in Wnt/ß-catenin signaling, we confirmed that this signaling pathway was activated in the myofibroblast differentiation of LR-MSCs. Targeted inhibition of Wnt/ß-catenin signaling by a small molecule, ICG-001, dose-dependently impeded the proliferation and transforming growth factor-ß1 (TGF-ß1)-mediated fibrogenic actions of LR-MSCs. In vivo, ICG-001 exerted its lung protective effects after bleomycin treatment through blocking mesenchymal-myofibroblast transition, repressing matrix gene expression, and reducing cell apoptosis. Moreover, delayed administration of ICG-001 attenuated bleomycin-induced lung fibrosis, which may present a promising therapeutic strategy for intervention of IPF. Interestingly, these antifibrotic actions of ICG-001 are operated by a mechanism independent of any disruption of Smad activation. In conclusion, our study demonstrated that Wnt/ß-catenin signaling may be an essential mechanism underlying the regulation of myofibroblast differentiation of LR-MSCs and their further participation in the development of pulmonary fibrosis.

Isolated talonavicular arthrodesis and talonavicular-cuneiform arthrodesis for the Müller-Weiss disease.

BACKGROUND: The study aimed to introduce the isolated talonavicular and talonavicular-cuneiform arthrodesis for the stage III and IV Müller-Weiss disease and analyze their clinical outcomes. METHODS: Thirty patients of stage III and IV Müller-Weiss disease were divided into the talonavicular (TN) arthrodesis group and the talonavicular-cuneiform (TNC) arthrodesis group according to the perinavicular osteoarthritis by MRI scans. For the isolated talonavicular arthrodesis group, 16 patients underwent talonavicular arthrodesis with two 4.0 mm hollow headless compression screws. For the TNC arthrodesis group, 14 patients were received the TNC arthrodesis with reverse "V" shape osteotomy and autoallergic iliac bone graft. All patients were followed up at 3, 6, 9, and 12 months, and per 6 months after 1 year, by the AOFAS ankle-midfoot scores, and evaluated by radiographic measurements. RESULTS: All of them were followed up in two groups and all patients were satisfied with their clinical results. At the TN arthrodesis group, the patients' mean was 39.8 months (range, 11-66 months) follow-up. The mean AOFAS ankle and hindfoot scores had improved from 38.3 ± 5.1 preoperatively to 88.9 ± 1.9 at the last postoperative assessment. At the TNC arthrodesis group, the mean follow-up was 51.7 months (range, 12-90 months). The mean AOFAS ankle and hindfoot scores were 40.1 ± 7.9 preoperatively to 90.1 ± 2.0 at the last postoperative. All of the cases were solid fusion on the radiograph. CONCLUSIONS: According to MRI evaluation, either TN or TNC arthrodesis for stage III or IV Müller-Weiss disease have the good clinical outcomes with solid fusion rate and obvious improvement of the quality of life of patients.

Individual headless compression screws fixed with three-dimensional image processing technology improves fusion rates of isolated talonavicular arthrodesis.

BACKGROUND: Screw fixation is a typical technique for isolated talonavicular arthrodesis (TNA), however, no consensus has been reached on how to select most suitable inserted position and direction. The study aimed to present a new fixation technique and to evaluate the clinical outcome of individual headless compression screws (HCSs) applied with three-dimensional (3D) image processing technology to isolated TNA. METHODS: From 2007 to 2014, 69 patients underwent isolated TNA by using double Acutrak HCSs. The preoperative three-dimensional (3D) insertion model of double HCSs was applied by Mimics, Catia, and SolidWorks reconstruction software. One HCS oriented antegradely from the edge of dorsal navicular tail where intersected interspace between the first and the second cuneiform into the talus body along the talus axis, and the other one paralleled the first screw oriented from the dorsal-medial navicular where intersected at the medial plane of the first cuneiform. The anteroposterior and lateral X-ray examinations certified that the double HCSs were placed along the longitudinal axis of the talus. Postoperative assessment included the American Orthopaedic Foot & Ankle Society hindfoot (AOFAS), the visual analogue scale (VAS) score, satisfaction score, imaging assessments, and complications. RESULTS: At the mean 44-months follow-up, all patients exhibited good articular congruity and solid bone fusion at an average of 11.26 ± 0.85 weeks (range, 10 ~ 13 weeks) without screw loosening, shifting, or breakage. The overall fusion rates were 100%. The average AOFAS score increased from 46.62 ± 4.6 (range, 37 ~ 56) preoperatively to 74.77 ± 5.4 (range, 64-88) at the final follow-up (95% CI: -30.86 ~ -27.34; p < 0.001). The mean VAS score decreased from 7.01 ± 1.2 (range, 4 ~ 9) to 1.93 ± 1.3 (range, 0 ~ 4) (95% CI: 4.69 ~ 5.48; p < 0.001). One cases (1.45%) and three cases (4.35%) experienced wound infection and adjacent arthritis respectively. The postoperative satisfaction score including pain relief, activities of daily living, and return to recreational activities were good to excellent in 62 (89.9%) cases. CONCLUSIONS: Individual 3D reconstruction of HCSs insertion model can be designed with three-dimensional image processing technology in TNA. The technology is safe, effective, and reliable to isolated TNA method with high bone fusion rates, low incidences of complications.

miR-877-3p targets Smad7 and is associated with myofibroblast differentiation and bleomycin-induced lung fibrosis.

Myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSC) plays an important role in idiopathic pulmonary fibrosis. By comparing the expression profiles of miRNAs before and after myofibroblast differentiation of LR-MSC, we identified miR-877-3p as a fibrosis-related miRNA. We found that miR-877-3p sequestration inhibited the myofibroblast differentiation of LR-MSC and attenuates bleomycin-induced lung fibrosis by targeting Smad7. Smad7, as an inhibitory smad in the TGF-ß1 signaling pathway, was decreased in the myofibroblast differentiation of LR-MSC and up-regulation of Smad7 could inhibit the differentiation process. Our data implicates a potential application of miR-877-3p as a fibrosis suppressor for pulmonary fibrosis therapy and also as a fibrosis marker for predicting prognosis.

The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells.

OBJECTIVES: Microcystin-leucine arginine (MC-LR) is produced by cyanobacteria and can accumulate in lungs through blood circulation. However, the effect of MC-LR on lung remains unclear. In this study, we investigated the chronic, low-dose effect of MC-LR on mouse lung tissues and the influence of MC-LR on mouse alveolar type II epithelial cells (ATII cells). METHODS: MC-LR was orally administered to mice at 0, 1, 10, and 40 µg/L for 6 consecutive months and mouse lungs were obtained for histopathological and immunoblot analysis. ATII cells were cultured in various concentrations of MC-LR (0, 0.5, 5, 50, 500 nmol/L) for indicated time and the cell viability and proteins change were tested. RESULTS: Our study revealed that the chronic, low-dose MC-LR exposure induced alveolar collapse and lung cell apoptosis as well as the breach of cell junction integrity. Furthermore, following treatment with MC-LR, ATII cells could uptake MC-LR, resulting in apoptosis and disruption of cell junction integrity. CONCLUSIONS: These data support the toxic potential of low-dose MC-LR in rendering chronic injury to lung tissues.

[Short-term effectiveness of suture anchor after debridement of extensor tendon insertion for recalcitrant lateral epicondylitis].

OBJECTIVE: To analyze the short-term effectiveness of repairing musculus extensor carpi radialis brevis (ECRB) and extensor digitorum communis (EDC) tendon using suture anchor after debridement of extensor tendon insertion for recalcitrant lateral epicondylitis. METHODS: Between March 2009 and May 2011, 10 patients (10 elbows) with recalcitrant lateral epicondylitis received repair of the ECRB and EDC tendon to the lateral epicondyle using a single suture anchor after debridement of extensor tendon insertion. There were 6 males and 4 females with an average age of 45.4 years (range, 36-57 years). The dominant elbow was involved in 8 patients and nondominant elbow in 2 patients; there were 4 manual workers and 6 ordinary workers. The disease duration ranged from 8 to 24 months (mean, 12.3 months). All patients had epicondylus lateralis humeri pain, local swelling and tenderness, and positive Mill sign. The average elbow range of motion (ROM) was 11.3 degrees (range, 0-30 degrees) in extension and was 132.5 degrees (range, 120-145 degrees) in flexion. Preoperative MRI showed external humeral epicondylitis in all patients. RESULTS: Primary wound healing was obtained in all patients without complications of infection, leakage of joint fluid, and stiffness of elbow. Ten patients were followed up 4 to 23 months with an average of 12 months (more than 12 months in 7 cases). The time to return to work was (3.75 +/- 0.95) months for manual workers and was (2.91 +/- 0.20) months for ordinary workers, showing no significant difference (t = 1.715, P = 0.180). Compared with preoperation, the mean visual analogue scale (VAS) score significantly decreased (P < 0.05), and Mayo score and the grip strength of dominant and nondominant significantly increased (P < 0.05), but no significant difference was found when compared with non-surgical side at last follow-up (P > 0.05). At last follow-up, the average ROM was -1.5 degrees (range, 0-10 degrees) in extension and was 150.5 degrees (range, 140-160 degrees) in flexion. CONCLUSION: To suture anchor for repairing the ECRB and EDC after debridement is a satisfactory procedure to treat recalcitrant lateral epicondylitis. It can effectively prevent loss of the forearm extensor strength, relieve the pain, recover the grip strength, and obtain good results.