Improving Right Ventricular Function by Increasing BMP Signaling with FK506.

Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation of BMP (bone morphogenetic protein) signaling with FK506 (tacrolimus) improved RV function by decreasing RV afterload. FK506 therapy further stabilized three patients with end-stage PAH. Whether FK506 has direct effects on the pressure-overloaded right ventricle is yet unknown. We hypothesized that increasing cardiac BMP signaling with FK506 improves RV structure and function in a model of fixed RV afterload after pulmonary artery banding (PAB). Direct cardiac effects of FK506 on the microvasculature and RV fibrosis were studied after surgical PAB in wild-type and heterozygous Bmpr2 mutant mice. RV function and strain were assessed longitudinally via cardiac magnetic resonance imaging during continuous FK506 infusion. Genetic lineage tracing of endothelial cells (ECs) was performed to assess the contribution of ECs to fibrosis. Molecular mechanistic studies were performed in human cardiac fibroblasts and ECs. In mice, low BMP signaling in the right ventricle exaggerated PAB-induced RV fibrosis. FK506 therapy restored cardiac BMP signaling, reduced RV fibrosis in a BMP-dependent manner independent from its immunosuppressive effect, preserved RV capillarization, and improved RV function and strain over the time course of disease. Endothelial mesenchymal transition was a rare event and did not significantly contribute to cardiac fibrosis after PAB. Mechanistically, FK506 required ALK1 in human cardiac fibroblasts as a BMPR2 co-receptor to reduce TGFß1-induced proliferation and collagen production. Our study demonstrates that increasing cardiac BMP signaling with FK506 improves RV structure and function independent from its previously described beneficial effects on pulmonary vascular remodeling.

Pulmonary arterial banding in mice may be a suitable model for studies on ventricular mechanics in pediatric pulmonary arterial hypertension.

BACKGROUND: The role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact of maintained pressure overload in the RV-pulmonary artery (PA) axis on myocardial strain and left ventricular (LV) mechanics in pediatric PAH patients in comparison to a preclinical PA-banding (PAB) mouse model. We hypothesize that the PAB mouse model mimics important aspects of interventricular mechanics of pediatric PAH and may be beneficial as a surrogate model for some longitudinal and interventional studies not possible in children. METHODS: Balanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) images of 18 PAH and 17 healthy (control) pediatric subjects were retrospectively analyzed using CMR feature-tracking (FT) software to compute measurements of myocardial strain. Furthermore, myocardial tagged-CMR images were also analyzed for each subject using harmonic phase flow analysis to derive LV torsion rate. Within 48 h of CMR, PAH patients underwent right heart catheterization (RHC) for measurement of PA/RV pressures, and to compute RV end-systolic elastance (RV_Ees, a measure of load-independent contractility). Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. bSSFP-CMR, tagged CMR, and intra-cardiac catheterization were performed on 12 PAB and 9 control mice (Sham) 7 weeks after surgery with identical post-processing as in the aforementioned patient studies. RV_Ees was assessed via the single beat method. RESULTS: LV torsion rate was significantly reduced under hypertensive conditions in both PAB mice (p = 0.004) and pediatric PAH patients (p < 0.001). This decrease in LV torsion rate correlated significantly with a decrease in RV_Ees in PAB (r = 0.91, p = 0.05) and PAH subjects (r = 0.51, p = 0.04). In order to compare combined metrics of LV torsion rate and strain parameters principal component analysis (PCA) was used. PCA revealed grouping of PAH patients with PAB mice and control subjects with Sham mice. Similar to LV torsion rate, LV global peak circumferential, radial, and longitudinal strain were significantly (p < 0.05) reduced under hypertensive conditions in both PAB mice and children with PAH. CONCLUSIONS: The PAB mouse model resembles PAH-associated myocardial mechanics and may provide a potential model to study mechanisms of RV/LV interdependency.

Photoacoustic Imaging of Embryonic Stem Cell-Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles.

The last decade has seen impressive progress in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that makes them ideal tools to repair injured hearts. To achieve an optimal outcome, advanced molecular imaging methods are essential to accurately track these transplanted cells in the heart. Herein, we demonstrate for the first time that a class of photoacoustic nanoparticles (PANPs) incorporating semiconducting polymers (SPs) as contrast agents can be used in the photoacoustic imaging (PAI) of transplanted hESC-CMs in living mouse hearts. This is achieved by virtue of two benefits of PANPs. First, strong PA signals and specific spectral features of SPs allow PAI to sensitively detect and distinguish a small number of PANP-labeled cells (2,000) from background tissues in vivo. Second, the PANPs show a high efficiency for hESC-CM labeling without adverse effects on cell structure, function, and gene expression. Assisted by ultrasound imaging, the delivery and engraftment of hESC-CMs in living mouse hearts can be assessed by PANP-based PAI with high spatial resolution (~100 µm). In summary, this study explores and validates a novel application of SPs as a PA contrast agent to track labeled cells with high sensitivity and accuracy in vivo, highlighting the advantages of integrating PAI and PANPs to advance cardiac regenerative therapies.

Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. Stem Cells 2017;35:2138-2149.

[Research on Test Method of Metallic Element Contained in Tea Based on EDXRF Technique].

As it has been certified by experimental testing that when using the energy-dispersive X-ray fluorescence (EDXRF) method to analyze the metallic elements contained in the tea the energy segment of effective X-ray fluorescence photons is located between 3 and 16 keV. Accordingly the spectral correction element is targeted at the copper elements located near the energy center(8 keV). The copper elements are also used as the picketage to be the standard curve. In the energy segment of effective X-ray fluorescence photons contained in the tea 1.25 mg · kg(-1) of the average detection limit was obtained by using the spiked method to analyze four elements of copper, iron, zinc and lead. Compared with the flame atomic absorption spectrum(FAAS), the actual relative error of the tested value by EDXRF is less than 6%, and the relative standard deviation is less than 5%. The result by T test shows that p > 0.05. The conclusions are that there are no statistically significant differences between EDXRF and FAAS. The measured results gained by the two methods agree with each other. And EDXRF can be used thoroughly to test the metal contents contained in the tea. The result shows that it is feasible to test the metallic contents contained in the tea by EDXRF, and its measured result can meet the requirements of field testing and analysis.

Measuring body layer vibration of vocal folds by high-frame-rate ultrasound synchronized with a modified electroglottograph.

The body-cover concept suggests that the vibration of body layer is an indispensable component of vocal fold vibration. To quantify this vibration, a synchronized system composed of a high-frame-rate ultrasound and a modified electroglottograph (EGG) was employed in this paper to simultaneously image the body layer vibration and record the vocal fold vibration phase information during natural phonations. After data acquisition, the displacements of in vivo body layer vibrations were measured from the ultrasonic radio frequency data, and the temporal reconstruction method was used to enhance the measurement accuracy. Results showed that the modified EGG, the waveform and characteristic points of which were identical to the conventional EGG, resolved the position conflict between the ultrasound transducer and EGG electrodes. The location and range of the vibrating body layer in the estimated displacement image were more clear and discernible than in the ultrasonic B-mode image. Quantitative analysis for vibration features of the body layer demonstrated that the body layer moved as a unit in the superior-inferior direction during the phonation of normal chest registers.

Characterization of the homogeneous tissue mixture approximation in breast imaging dosimetry.

PURPOSE: To compare the estimate of normalized glandular dose in mammography and breast CT imaging obtained using the actual glandular tissue distribution in the breast to that obtained using the homogeneous tissue mixture approximation. METHODS: Twenty volumetric images of patient breasts were acquired with a dedicated breast CT prototype system and the voxels in the breast CT images were automatically classified into skin, adipose, and glandular tissue. The breasts in the classified images underwent simulated mechanical compression to mimic the conditions present during mammographic acquisition. The compressed thickness for each breast was set to that achieved during each patient's last screening cranio-caudal (CC) acquisition. The volumetric glandular density of each breast was computed using both the compressed and uncompressed classified images, and additional images were created in which all voxels representing adipose and glandular tissue were replaced by a homogeneous mixture of these two tissues in a proportion corresponding to each breast's volumetric glandular density. All four breast images (compressed and uncompressed; heterogeneous and homogeneous tissue) were input into Monte Carlo simulations to estimate the normalized glandular dose during mammography (compressed breasts) and dedicated breast CT (uncompressed breasts). For the mammography simulations the x-ray spectra used was that used during each patient's last screening CC acquisition. For the breast CT simulations, two x-ray spectra were used, corresponding to the x-ray spectra with the lowest and highest energies currently being used in dedicated breast CT prototype systems under clinical investigation. The resulting normalized glandular dose for the heterogeneous and homogeneous versions of each breast for each modality was compared. RESULTS: For mammography, the normalized glandular dose based on the homogeneous tissue approximation was, on average, 27% higher than that estimated using the true heterogeneous glandular tissue distribution (Wilcoxon Signed Rank Test p = 0.00046). For dedicated breast CT, the overestimation of normalized glandular dose was, on average, 8% (49 kVp spectrum, p = 0.00045) and 4% (80 kVp spectrum, p = 0.000089). Only two cases in mammography and two cases in dedicated breast CT with a tube voltage of 49 kVp resulted in lower dose estimates for the homogeneous tissue approximation compared to the heterogeneous tissue distribution. CONCLUSIONS: The normalized glandular dose based on the homogeneous tissue mixture approximation results in a significant overestimation of dose to the imaged breast. This overestimation impacts the use of dose estimates in absolute terms, such as for risk estimates, and may impact some comparative studies, such as when modalities or techniques with different x-ray energies are used. The error introduced by the homogeneous tissue mixture approximation in higher energy x-ray modalities, such as dedicated breast CT, although statistically significant, may not be of clinical concern. Further work is required to better characterize this overestimation and potentially develop new metrics or correction factors to better estimate the true glandular dose to breasts undergoing imaging with ionizing radiation.

Image-level supervised segmentation for human organs with confidence cues.

Image segmentation for human organs is an important task for the diagnosis and treatment of diseases. Current deep learning-based methods are fully supervised and need pixel-level labels. Since the medical images are highly specialized and complex, the work of delineating pixel-level segmentation masks is very time-consuming. Weakly supervised methods are then chosen to lighten the workload, which only needs physicians to determine whether an image contains the organ regions of interest. These weakly supervised methods have a common drawback, in that they do not incorporate prior knowledge that alleviates the lack of pixel-level information for segmentation. In this work, we propose a weakly supervised method based on prior knowledge for the segmentation of human organs. The proposed method was validated on three data sets of human organ segmentation. Experimental results show that the proposed image-level supervised segmentation method outperforms several state-of-the-art methods.

Method for selective ablation of undifferentiated human pluripotent stem cell populations for cell-based therapies.

Human pluripotent stem cells (PSCs), which are composed of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an opportunity to advance cardiac cell therapy-based clinical trials. However, an important hurdle that must be overcome is the risk of teratoma formation after cell transplantation due to the proliferative capacity of residual undifferentiated PSCs in differentiation batches. To tackle this problem, we propose the use of a minimal noncardiotoxic doxorubicin dose as a purifying agent to selectively target rapidly proliferating stem cells for cell death, which will provide a purer population of terminally differentiated cardiomyocytes before cell transplantation. In this study, we determined an appropriate in vitro doxorubicin dose that (a) eliminates residual undifferentiated stem cells before cell injection to prevent teratoma formation after cell transplantation and (b) does not cause cardiotoxicity in ESC-derived cardiomyocytes (CMs) as demonstrated through contractility analysis, electrophysiology, topoisomerase activity assay, and quantification of reactive oxygen species generation. This study establishes a potentially novel method for tumorigenic-free cell therapy studies aimed at clinical applications of cardiac cell transplantation.

The left ventricle undergoes biomechanical and gene expression changes in response to increased right ventricular pressure overload.

Pulmonary hypertension (PH) results in right ventricular (RV) pressure overload and eventual failure. Current research efforts have focused on the RV while overlooking the left ventricle (LV), which is responsible for mechanically assisting the RV during contraction. The objective of this study is to evaluate the biomechanical and gene expression changes occurring in the LV due to RV pressure overload in a mouse model. Nine male mice were divided into two groups: (a) pulmonary arterial banding (PAB, N = 4) and (b) sham surgery (Sham, N = 5). Tagged and steady-state free precision cardiac MRI was performed on each mouse at 1, 4, and 7 weeks after surgery. At/week7, the mice were euthanized following right/left heart catheterization with RV/LV tissue harvested for histology and gene expression (using RT-PCR) studies. Compared to Sham mice, the PAB group revealed a significantly decreased LV and RV ejection fraction, and LV maximum torsion and torsion rate, within the first week after banding. In the PAB group, there was also a slight but significant increase in LV perivascular fibrosis, which suggests elevated myocardial stress. LV fibrosis was also accompanied with changes in gene expression in the hypertensive group, which was correlated with LV contractile mechanics. In fact, principal component (PC) analysis of LV gene expression effectively separated Sham and PAB mice along PC2. Changes in LV contractile mechanics were also significantly correlated with unfavorable changes in RV contractile mechanics, but a direct causal relationship was not established. In conclusion, a purely biomechanical insult of RV pressure overload resulted in biomechanical and transcriptional changes in both the RV and LV. Given that the RV relies on the LV for contractile energy assistance, considering the LV could provide prognostic and therapeutic targets for treating RV failure in PH.

Modeling Secondary Iron Overload Cardiomyopathy with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Excessive iron accumulation in the heart causes iron overload cardiomyopathy (IOC), which initially presents as diastolic dysfunction and arrhythmia but progresses to systolic dysfunction and end-stage heart failure when left untreated. However, the mechanisms of iron-related cardiac injury and how iron accumulates in human cardiomyocytes are not well understood. Herein, using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we model IOC and screen for drugs to rescue the iron overload phenotypes. Human iPSC-CMs under excess iron exposure recapitulate early-stage IOC, including oxidative stress, arrhythmia, and contractile dysfunction. We find that iron-induced changes in calcium kinetics play a critical role in dysregulation of CM functions. We identify that ebselen, a selective divalent metal transporter 1 (DMT1) inhibitor and antioxidant, could prevent the observed iron overload phenotypes, supporting the role of DMT1 in iron uptake into the human myocardium. These results suggest that ebselen may be a potential preventive and therapeutic agent for treating patients with secondary iron overload.

Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates.

Transposable elements (TEs) comprise nearly half of the human genome and are often transcribed or exhibit cis-regulatory properties with unknown function in specific processes such as heart development. In the case of endogenous retroviruses (ERVs), a TE subclass, experimental interrogation is constrained as many are primate-specific or human-specific. Here, we use primate pluripotent stem-cell-derived cardiomyocytes that mimic fetal cardiomyocytes in vitro to discover hundreds of ERV transcripts from the primate-specific MER41 family, some of which are regulated by the cardiogenic transcription factor TBX5. The most significant of these are located within BANCR, a long non-coding RNA (lncRNA) exclusively expressed in primate fetal cardiomyocytes. Functional studies reveal that BANCR promotes cardiomyocyte migration in vitro and ventricular enlargement in vivo. We conclude that recently evolved TE loci such as BANCR may represent potent de novo developmental regulatory elements that can be interrogated with species-matching pluripotent stem cell models.

Adaptive deep learning for head and neck cancer detection using hyperspectral imaging.

It can be challenging to detect tumor margins during surgery for complete resection. The purpose of this work is to develop a novel learning method that learns the difference between the tumor and benign tissue adaptively for cancer detection on hyperspectral images in an animal model. Specifically, an auto-encoder network is trained based on the wavelength bands on hyperspectral images to extract the deep information to create a pixel-wise prediction of cancerous and benign pixel. According to the output hypothesis of each pixel, the misclassified pixels would be reclassified in the right prediction direction based on their adaptive weights. The auto-encoder network is again trained based on these updated pixels. The learner can adaptively improve the ability to identify the cancer and benign tissue by focusing on the misclassified pixels, and thus can improve the detection performance. The adaptive deep learning method highlighting the tumor region proved to be accurate in detecting the tumor boundary on hyperspectral images and achieved a sensitivity of 92.32% and a specificity of 91.31% in our animal experiments. This adaptive learning method on hyperspectral imaging has the potential to provide a noninvasive tool for tumor detection, especially, for the tumor whose margin is indistinct and irregular.

Histopathology Feature Mining and Association with Hyperspectral Imaging for the Detection of Squamous Neoplasia.

Hyperspectral imaging (HSI) is a noninvasive optical modality that holds promise for early detection of tongue lesions. Spectral signatures generated by HSI contain important diagnostic information that can be used to predict the disease status of the examined biological tissue. However, the underlying pathophysiology for the spectral difference between normal and neoplastic tissue is not well understood. Here, we propose to leverage digital pathology and predictive modeling to select the most discriminative features from digitized histological images to differentiate tongue neoplasia from normal tissue, and then correlate these discriminative pathological features with corresponding spectral signatures of the neoplasia. We demonstrated the association between the histological features quantifying the architectural features of neoplasia on a microscopic scale, with the spectral signature of the corresponding tissue measured by HSI on a macroscopic level. This study may provide insight into the pathophysiology underlying the hyperspectral dataset.

An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium.

A major challenge in myocardial infarction (MI)-related heart failure treatment using microRNA is the efficient and sustainable delivery of miRNAs into myocardium to achieve functional improvement through stimulation of intrinsic myocardial restoration. In this study, we established an in vivo delivery system using polymeric nanoparticles to carry miRNA (miNPs) for localized delivery within a shear-thinning injectable hydrogel. The miNPs triggered proliferation of human embryonic stem cell-derived cardiomyocytes and endothelial cells (hESC-CMs and hESC-ECs) and promoted angiogenesis in hypoxic conditions, showing significantly lower cytotoxicity than Lipofectamine. Furthermore, one injected dose of hydrogel/miNP in MI rats demonstrated significantly improved cardiac functions: increased ejection fraction from 45% to 64%, reduced scar size from 20% to 10%, and doubled capillary density in the border zone compared to the control group at 4 weeks. As such, our results indicate that this injectable hydrogel/miNP composite can deliver miRNA to restore injured myocardium efficiently and safely.

[Treatment strategy for flail foot with sensory disorder of spina bifida sequela in adult].

Objective: To summarize the main methods and comprehensive effects of limited surgery combined with external fixation for the treatment of flail foot with sensory disorder of spina bifida sequela in adult. Method: The clinical data of 22 cases (30 feet) of the adult spina bifida sequela who suffered from flail foot with sensory disorder and treated by limited surgery combined with external fixation were retrospectively analysed between January 2005 and December 2015. There were 14 males and 8 females with an age of 8-38 years (mean, 21.5 years). All 30 feet were distal ankle sensory loss, including 2 cases (2 feet) on the left side, 2 cases (2 feet) on the right side, and 18 cases (26 feet) on both sides. There was 1 foot accompanied by ulcerative plantar ulcers, and 3 feet lost their toes due to foot osteomyelitis in the weight-bearing area. Combined with 3 cases of hip dislocation, 3 cases of scoliosis, 4 cases of knee deformity, and 3 cases of ptosis. There were 5 cases of normal control of urine and stool, 10 cases of partial control of urine and stool, 6 cases of overflow urinary incontinence, and 1 case of cystostomy. According to X-ray film, the lesion of spina bifida was evaluated, the laminar insufficiency was located at L 3-L 5 in 8 cases, L 5, S 1 in 9 cases, and L 3-S 3 in 5 cases. In the patients, 12 feet were performed ankle joint arthrodesis, 10 feet subtalar arthrodesis, and 8 feet tibia-talus-calcaneus arthrodesis. Ilizarov external fixator was used in 18 feet, Hybrid fixator in 8 feet, Hybrid fixator and cannulate screws in 3 feet, and Ilizarov fixator and cannulate screws in 1 foot. Results: All 22 patients were followed up 10-80 months (mean, 48.5 months). All ankle deformities were corrected effectively after operation, the middle and hind feet were stable, the plantar foot was restored, the whole foot was loaded, and the ulcer healed without recurrence. There were 2 cannulate screws ruptured in the subtalar arthrodesis, bone healed after screws break; no complication such as surgical infection, neurovascular injury, and so on happened. At last follow-up, based on the evaluation criteria of QIN Sihe lower limb deformity correction, the results were excellent in 15 feet, good in 9 feet, and fair in 6 feet, with an excellent and good rate of 80.0%. Conclusion: The treatment of flail foot with sensory disorder of spina bifida sequela is more demanding. The limited surgeries combined with external fixation play an important role for recovering the stability of foot and ankle, better clinical results, and less complications.

Detection and delineation of squamous neoplasia with hyperspectral imaging in a mouse model of tongue carcinogenesis.

Hyperspectral imaging (HSI) holds the potential for the noninvasive detection of cancers. Oral cancers are often diagnosed at a late stage when treatment is less effective and the mortality and morbidity rates are high. Early detection of oral cancer is, therefore, crucial in order to improve the clinical outcomes. To investigate the potential of HSI as a noninvasive diagnostic tool, an animal study was designed to acquire hyperspectral images of in vivo and ex vivo mouse tongues from a chemically induced tongue carcinogenesis model. A variety of machine-learning algorithms, including discriminant analysis, ensemble learning, and support vector machines, were evaluated for tongue neoplasia detection using HSI and were validated by the reconstructed pathological gold-standard maps. The diagnostic performance of HSI, autofluorescence imaging, and fluorescence imaging were compared in this study. Color-coded prediction maps were generated to display the predicted location and distribution of premalignant and malignant lesions. This study suggests that hyperspectral imaging combined with machine-learning techniques can provide a noninvasive tool for the quantitative detection and delineation of squamous neoplasia.

[Data analysis of 8 113 cases of limb deformities corrected by external fixation].

Objective: To analyze the data of external fixation instruments (including Ilizarov instruments) used by QIN Sihe orthopaedic surgical team in the treatment of limb deformities in the past 30 years, and to explore the indications for the application of modern external fixation techniques in the correction of limb deformities and individual device configuration selection strategy. Methods: According to QIN Sihe orthopaedic surgical team, the use of external fixator between January 1988 and December 2017 was analyzed retrospectively. The total use of external fixation and the proportion of different external fixators were analyzed in gender, different operation time, different age, different parts, and different diseases. Results: External fixators were used in 8 113 patients, 69 of them were used simultaneously in both lower extremity surgery, so 8 182 external fixators were used. Among them, there were 4 725 (57.74%) combined external fixators, 3 388 (41.41%) Ilizarov circle fixators, 64 (0.78%) single arm external fixators (including Orthofix), 5 (0.06%) Taylor space external fixators. There were 4 487 males (55.31%) and 3 626 females (44.69%). According to the analysis of different time periods, the number of external fixators increased year by year, and the number of applications increased after 2000. The main age of the patients was 11-30 years old, of which 1 819 sets (22.23%) were used at the age of 21-25 years. The use of the external fixator covered almost all parts of the limbs, with the ankle and toe areas being the most common, reaching 4 664 sets (57.00%), and the upper extremities the least, with 152 sets (1.86%). The 8 113 cases covered more than a dozen disciplines and more than 150 kinds of diseases. The top 5 diseases were poliomyelitis sequelae, cerebral palsy, deformity of lower extremity after spina bifida, traumatic sequelae, and congenital equinovarus foot. Conclusion: Ilizarov technique has been widely used in extremity deformity, disability, and complicated orthopedic diseases caused by vascular, lymphoid, nerve, skin, endocrine, and other diseases. The indication of operation is far beyond the scope of orthopedics. The domestic external fixator and its mounting tools can basically meet the requirements of various treatments. The technique of external fixation has entered a new era of tension tissue regeneration under stress control, natural repair of tissue trauma and deformity, and reconstruction of limb function.

Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction.

Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 107 NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9-14/group) at 4 days after 60-min coronary artery occlusion-reperfusion. Cardiac function and left ventricular remodeling were similarly improved in both iPSC-CM-treated groups. To mimic the ischemic environment in the infarcted heart, both cultured NHP and human iPSC-CMs underwent 24-hr hypoxia in vitro. Both cells and media were collected, and similarities in transcriptomic as well as metabolomic profiles were noted between both groups. In conclusion, both NHP and human iPSC-CMs confer similar cardioprotection in a rodent myocardial infarction model through relatively similar mechanisms via promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis.