Combining balloon catheter expansion with swallowing training can better improve the swallowing of tracheotomy patients after pontine hemorrhage / 中华物理医学与康复杂志

Objective:To observe any effect of supplementing basic swallowing training with balloon catheter dilation on the swallowing function of tracheostomy patients with pontine hemorrhage.Methods:A total of 40 pontine hemorrhage patients with tracheostomy and swallowing disorders were divided randomly into an observation group and a control group, each of 20. Both groups were given nutritional neurodrugs and basic swallowing training, but the observation group also received 25 minutes of balloon catheter dilation, five times a week for 6 weeks. Before and after the 6 weeks of treatment one swallowing therapist evaluated the feeding ability and leakage-aspiration status of each subject assigning functional oral intake (FOIS) ratings and Rosenbek Leakage/Aspiration Rating Scale (PAS) ratings double-blinded. The Watian water swallowing test was also applied.Results:After the treatment the average FOIS and PAS scores of both groups had improved significantly, with those of the observation group then significantly better than among the control group on average. The total treatment effectiveness rate was 70% in the observation group, significantly better than the 30% in the control group.Conclusion:Supplementing swallowing training with balloon catheter dilation can better improve the swallowing of patients recovering from a tracheotomy after pontine hemorrhage.

Robot-assisted virtual scenario training combined with scalp acupuncture can relieve cognitive impairment among stroke survivors / 中华物理医学与康复杂志

Objective:To explore any effect of combining robot-assisted virtual scenario training of the upper limbs with scalp acupuncture on post-stroke cognitive impairment.Methods:Ninety patients with post-stroke cognitive impairment (PSCI) were divided at random into a control group, a scalp acupuncture group and a comprehensive group, each of 30. In addition to routine health education and rehabilitation training, the scalp acupuncture group was given scalp acupuncture, while the comprehensive group was treated with scalp acupuncture and virtual scenario training with an upper limb robot. Before and after 4 weeks of the treatment, the subjects′ cognitive functioning was assessed using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment scale (MoCA). Ability in the activities of daily living (ADL) was quantified using the Modified Barthel Index (MBI).Results:After the intervention, significant improvement was observed in the average MMSE, MoCA and MBI scores of all three groups. The average MMSE and MBI scores of the scalp acupuncture group were then significantly higher than the control group′s averages, while the average MMSE, MoCA and MBI scores of the comprehensive group were all significantly better than those of the other two groups.Conclusion:Robot-assisted virtual scenario upper limb training combined with scalp acupuncture can significantly improve the cognition and ADL ability of PSCI patients.

Cardiothoracic ratio values and trajectories are associated with risk of requiring dialysis and mortality in chronic kidney disease.

BACKGROUND: The prognostic role of the cardiothoracic ratio (CTR) in chronic kidney disease (CKD) remains undetermined. METHODS: We conducted a retrospective cohort study of 3117 patients with CKD aged 18-89 years who participated in an Advanced CKD Care Program in Taiwan between 2003 and 2017 with a median follow up of 1.3(0.7-2.5) and 3.3(1.8-5.3) (IQR) years for outcome of end-stage renal disease (ESRD) and overall death, respectively. We developed a machine learning (ML)-based algorithm to calculate the baseline and serial CTRs, which were then used to classify patients into trajectory groups based on latent class mixed modelling. Association and discrimination were evaluated using multivariable Cox proportional hazards regression analyses and C-statistics, respectively. RESULTS: The median (interquartile range) age of 3117 patients is 69.5 (59.2-77.4) years. We create 3 CTR trajectory groups (low [30.1%], medium [48.1%], and high [21.8%]) for the 2474 patients with at least 2 CTR measurements. The adjusted hazard ratios for ESRD, cardiovascular mortality, and all-cause mortality in patients with baseline CTRs ≥0.57 (vs CTRs <0.47) are 1.35 (95% confidence interval, 1.06-1.72), 2.89 (1.78-4.71), and 1.50 (1.22-1.83), respectively. Similarly, greater effect sizes, particularly for cardiovascular mortality, are observed for high (vs low) CTR trajectories. Compared with a reference model, one with CTR as a continuous variable yields significantly higher C-statistics of 0.719 (vs 0.698, P = 0.04) for cardiovascular mortality and 0.697 (vs 0.693, P < 0.001) for all-cause mortality. CONCLUSIONS: Our findings support the real-world prognostic value of the CTR, as calculated by a ML annotation tool, in CKD. Our research presents a methodological foundation for using machine learning to improve cardioprotection among patients with CKD.

An enlarged heart occurs during various medical conditions and can result in early death. However, it is unclear whether this is also the case in patients with chronic kidney disease (CKD). Although the size of the heart can be measured on chest X-rays, this process is time consuming. We used artificial intelligence to quantify the heart size of 3117 CKD patients based on their chest X-rays within hours. We found that CKD patients with an enlarged heart were more likely to develop end-stage kidney disease or die. This could improve monitoring of CKD patients with an enlarged heart and improve their care.

Biofeedback training can significantly improve dysphagia among stroke survivors / 中华物理医学与康复杂志

Objective:To observe any effect of combining surface electromyography biofeedback with intensive pharyngeal ascending e-biofeedback training on dysphagia among stroke survivors.Methods:Sixty stroke survivors with dysphagia were randomly divided into a biofeedback group, a pharyngeal ascending group and a combination group, each of 20. In addition to routine swallowing training, the biofeedback group received 20 minutes of surface electromyographic biofeedback training daily while the pharyngeal ascending group did pharyngeal rising reinforcement training based on biofeedback for strength and skill training (BiSSkiT) theory. The combination group was given both. Before and after 4 weeks of the interventions, videofluoroscopy was used to evaluate everyone′s swallowing. The Swallowing Function Assessment Scale (SSA) and the Dysphagia Outcome and Severity Scale (DOSS) were also applied.Results:Significant improvement was observed in all 3 groups in terms of their average VFSS, SSA and DOSS scores. The average videofluoroscopy, SSA and DOSS results of the combination group were then significantly better than the other two groups′ averages, and those of the pharyngeal ascending group were significantly superior to those of the biofeedback group.Conclusion:Combining intensive pharyngeal ascending electronic biofeedback training with surface EMG biofeedback can significantly improve the swallowing function of stroke survivors.

Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Application of machine learning methods for the prediction of true fasting status in patients performing blood tests.

The fasting blood glucose (FBG) values extracted from electronic medical records (EMR) are assumed valid in existing research, which may cause diagnostic bias due to misclassification of fasting status. We proposed a machine learning (ML) algorithm to predict the fasting status of blood samples. This cross-sectional study was conducted using the EMR of a medical center from 2003 to 2018 and a total of 2,196,833 ontological FBGs from the outpatient service were enrolled. The theoretical true fasting status are identified by comparing the values of ontological FBG with average glucose levels derived from concomitant tested HbA1c based on multi-criteria. In addition to multiple logistic regression, we extracted 67 features to predict the fasting status by eXtreme Gradient Boosting (XGBoost). The discrimination and calibration of the prediction models were also assessed. Real-world performance was gauged by the prevalence of ineffective glucose measurement (IGM). Of the 784,340 ontologically labeled fasting samples, 77.1% were considered theoretical FBGs. The median (IQR) glucose and HbA1c level of ontological and theoretical fasting samples in patients without diabetes mellitus (DM) were 94.0 (87.0, 102.0) mg/dL and 5.6 (5.4, 5.9)%, and 92.0 (86.0, 99.0) mg/dL and 5.6 (5.4, 5.9)%, respectively. The XGBoost showed comparable calibration and AUROC of 0.887 than that of 0.868 in multiple logistic regression in the parsimonious approach and identified important predictors of glucose level, home-to-hospital distance, age, and concomitantly serum creatinine and lipid testing. The prevalence of IGM dropped from 27.8% based on ontological FBGs to 0.48% by using algorithm-verified FBGs. The proposed ML algorithm or multiple logistic regression model aids in verification of the fasting status.

Combining biofeedback based on virtual reality technology with transcranial magnetic stimulation aids the recovery of dysphagic stroke survivors / 中华物理医学与康复杂志

Objective:To observe the effect of combining biofeedback therapy (BFT) based on virtual reality technology with repeated transcranial magnetic stimulation (rTMS) on dysphagia among stroke survivors.Methods:Eighty patients were randomly divided into a control group, an rTMS group, a BFT group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the rTMS and BFT groups were given those treatments, while the combined treatment group was given both for 4 weeks. Swallowing function was evaluated before and after the treatment using the standardized swallowing assessment (SSA) and the functional oral intake scale (FOIS). Videofluoroscopy was used to quantify the subjects′ oral and pharyngeal phases and their aspiration status.Results:Significant improvement was observed in the average FOIS and SSA scores, as well as in the average oral and pharyngeal phases and in aspiration. The combined treatment group′s results were significantly better in all those aspects than those of the other 3 groups.Conclusion:The combined application of biofeedback therapy based on virtual reality technology and repeated transcranial magnetic stimulation can improve the swallowing function of stroke survivors with dysphagia. It is worthy of clinical promotion.

Parameters optimization in Heparin affinity chromatography purification of human coagulation factor Ⅸ / 中国输血杂志

【Objective】 To optimize the purification conditions of heparin affinity chromatography in the purification of human coagulation factor Ⅸ by response surface method and establish the optimal chromatography process parameters. 【Methods】 The effect of sample loading temperature on purification efficiency was analyzed through single factor test. Three-factor three-level response surface method was used to optimize the chromatographic elution conditions. The Folin phenol method and the automatic hemagglutination analyzer were used to determine the total protein content and human coagulation factor Ⅸ titer, respectively. The purification effect was evaluated by activity index and process recovery rate. 【Results】 The optimized optimal chromatographic conditions were loading at 5 ℃, washing 4 CV, eluent formulation of sodium citrate 20 mmol/L, arginine hydrochloride 18.7 mmol/L, NaCl 611.6 mmol/L and pH 7.5; under this optimal setting, the recovery rate of the chromatographic process was (46.6±2.9) %, titer of factor Ⅸ rated to (68.4±4.7) IU/mL and specific activity was (62.8±3.3) IU/mg. 【Conclusion】 The optimized parameters of heparin affinity chromatography process by response surface method can produce better purification effect on human coagulation factor Ⅸ.

Electroacupuncture enhances the effectiveness of electrical stimulation in treating spastic foot drop / 中华物理医学与康复杂志

Objective:To observe the clinical effect of combining four-channel electrical stimulation with electroacupuncture of the antagonistic muscles in treating post-stroke spastic foot drop.Methods:Ninety stroke survivors with spastic foot drop were randomly divided into a control group, an electrical stimulation group and an observation group, each of 30. In addition to routine rehabilitation training, the electrical stimulation group was given four-channel electrical stimulation for 4 weeks, the electrical stimulation was delivered with a pulse duration of 200μs and an intensity of motor threshold at 30Hz, while the observation group also received electroacupuncture of the antagonistic muscle. Before and after the treatment, the three groups were evaluated using the clinical spasticity index (CSI). Stride frequency, stride length, and the supporting and swing phases on the affected side were also measured. Electromyography (EMG) was also conducted.Results:After the treatment, the average CSI scores of all groups had decreased significantly, with that of the observation group significantly lower than the electrical stimulation group and control group′s averages. The average gait descriptors of the three groups had also improved significantly, with significantly greater improvement in the observation group than in the other two. The average H reflex latency was significantly longer and Hmax/Mmax was significantly smaller in all three groups, but the observation group′s average values were again significantly better than those of the electrical stimulation group.Conclusion:Electroacupuncture of the antagonistic muscle enhances the effectiveness of four-channel electrical stimulation in relieving foot drop symptoms and improving gait after a stroke.

Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis

Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting "Warburg effect" compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H

The construction of nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration

In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. The differentiation of M cells was observed by up-regulated expression of Sialyl Lewis A antigen (SLAA) and integrin 1, and down-regulated activity of alkaline phosphatase. After targeting M cells with iRGD peptide (cRGDKGPDC), the transport of nanoparticles increased. , the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration. In the evaluation of immune effect , the nasal administration of OVA-PLGA/iRGD led to more release of IgG, IFN-, IL-2 and secretory IgA (sIgA) compared with OVA@PLGA group. Collectively, the study constructed M cell model, and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.

Advances in tumor microenvironment responsive and regulatory drug delivery system / 药学学报

The complexity of tumor microenvironment brings both challenges and opportunities for targeted drug delivery. On the one hand, using the special characteristic as stimuli, we can construct a variety of responsive drug delivery systems for tumor targeting. On the other hand, the abnormal vasculature and dense extracellular matrix in solid tumor become formidable barriers to the nanoparticles delivery, which greatly reduces the drug delivery efficiency. Lots of researches focus on regulating the tumor microenvironment to make it more conducive to drug delivery. In this review, we will highlight the recent advances both in tumor microenvironment responsive nano-drug delivery systems design and tumor microenvironment regulation to improve tumor targeted delivery efficiency, and discuss the existing problems and future development.

The progress and perspective of nanoparticle-enabled tumor metastasis treatment

As one of the most serious threats to human being, cancer is hard to be treated when metastasis happens. What's worse, there are few identified targets of metastasis for drug development. Therefore, it is important to develop strategies to prevent metastasis or treat existed metastasis. This review focuses on the procedure of metastasis, and first summarizes the targeting delivery strategies, including primary tumor targeting drug delivery, tumor metastasis targeting drug delivery and hijacking circulation cells. Then, as a promising treatment, the application of immunotherapy in tumor metastasis treatment is introduced, and strategies that stimulating immune response are reviewed, including chemotherapy, photothermal therapy, photodynamic therapy, ferroptosis, sonodynamic therapy, and nanovaccines. Finally, the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.

Microecology research: a new target for the prevention of asthma / 中华医学杂志(英文版)

The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.

Lattice Boltzmann-Discrete Element Modeling Simulation of SCC Flowing Process for Rock-Filled Concrete.

Since invented in 2003, rock-filled concrete (RFC) has gained much attention and has been successfully applied in more and more civil and hydraulic projects in China. This study developed a numerical framework to simulate self-compacting concrete (SCC) flows in the voids among rocks of RFC, which couples the lattice Boltzmann method and discrete element method (DEM). The multiple-relaxation-time scheme is used to simulate self-compacting mortar (SCM) for better stability while the motion of coarse aggregates in SCC is simulated with DEM. The immersed moving boundary method is incorporated to deal with the interactions between coarse aggregates and SCM. After validation, the coupled framework is applied to study SCC flows in a single channel and in porous media with multi-channels. A passing factor PF was proposed and calculated to describe quantitatively the passing ability of SCC through a single channel. The study found that jamming of SCC occurs when the ratio Ar of the gap width to particle diameter is smaller than 2.0 and the jamming risk increases with solid particles fraction while the passing ability has a weak relation with the pressure gradient. Further, SCC flow is self-tuning in porous media with multi-channels and it is prone to go through larger or wider gaps. Exceeded existence of narrow gaps will significantly increase the jamming risk.

Artificial intelligence-based decision-making for age-related macular degeneration.

Artificial intelligence (AI) based on convolutional neural networks (CNNs) has a great potential to enhance medical workflow and improve health care quality. Of particular interest is practical implementation of such AI-based software as a cloud-based tool aimed for telemedicine, the practice of providing medical care from a distance using electronic interfaces. Methods: In this study, we used a dataset of labeled 35,900 optical coherence tomography (OCT) images obtained from age-related macular degeneration (AMD) patients and used them to train three types of CNNs to perform AMD diagnosis. Results: Here, we present an AI- and cloud-based telemedicine interaction tool for diagnosis and proposed treatment of AMD. Through deep learning process based on the analysis of preprocessed optical coherence tomography (OCT) imaging data, our AI-based system achieved the same image discrimination rate as that of retinal specialists in our hospital. The AI platform's detection accuracy was generally higher than 90% and was significantly superior (p < 0.001) to that of medical students (69.4% and 68.9%) and equal (p = 0.99) to that of retinal specialists (92.73% and 91.90%). Furthermore, it provided appropriate treatment recommendations comparable to those of retinal specialists. Conclusions: We therefore developed a website for realistic cloud computing based on this AI platform, available at https://www.ym.edu.tw/~AI-OCT/. Patients can upload their OCT images to the website to verify whether they have AMD and require treatment. Using an AI-based cloud service represents a real solution for medical imaging diagnostics and telemedicine.

Theranostic nanoparticles with tumor-specific enzyme-triggered size reduction and drug release to perform photothermal therapy for breast cancer treatment

Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency, nanoparticles need to change size so as to fully utilize the enhanced permeability and retention (EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin (BSA) protected gold nanocluster (AuNC@CBSA, 21.06 nm) to both load indocyanine green (ICG) and act as imaging probe to realize theranostic. Then AuNC@CBSA-ICG was fabricated with negatively charged hyaluronic acid (HA) to form AuNC@CBSA-ICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed AuNC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter or , AuNC@CBSA-ICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated AuNC@CBSA-ICG@HA was potential for breast cancer therapy.

Effect of Sling Exercise Therapy on Chronic Nonspecific Low Back Pain / 中国康复理论与实践

Objective:To observe the effect of sling exercise therapy on chronic nonspecific low back pain. Methods:From February, 2017 to February, 2018, 84 patients with chronic nonspecific low back pain were randomly divided into control group and observation group, with 42 cases in each group. The observation group was treated with the combination of the sling exercise therapy and acupuncture, and the control group only received acupuncture. They were assessed with Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) before treatment, one month after treatment and at three-month follow-up. Results:Before treatment, there was no statistically significant difference in the scores of VAS and ODI between two groups (t < 1.638, P > 0.05). One month after treatment and at three-month follow-up, the scores of VAS and ODI decreased in both groups (P < 0.01). Compared with one month after treatment, the scores of VAS and ODI increased in the control group at three-month follow-up (t > 2.219, P < 0.05), however, no difference was found in the observation group (t < 1.738, P > 0.05). One month after treatment, the scores of VAS and ODI were lower in the observation group than in the control group (t > 3.535, P < 0.001). Conclusion:Sling exercise therapy combined with acupuncture is superior to simple acupuncture in treating chronic nonspecific low back pain, and the curative effect is persistent.

Plant stress RNA-seq Nexus: a stress-specific transcriptome database in plant cells.

BACKGROUND: Abiotic and biotic stresses severely affect the growth and reproduction of plants and crops. Determining the critical molecular mechanisms and cellular processes in response to stresses will provide biological insight for addressing both climate change and food crises. RNA sequencing (RNA-Seq) is a revolutionary tool that has been used extensively in plant stress research. However, no existing large-scale RNA-Seq database has been designed to provide information on the stress-specific differentially expressed transcripts that occur across diverse plant species and various stresses. RESULTS: We have constructed a comprehensive database, the plant stress RNA-Seq nexus (PSRN), which includes 12 plant species, 26 plant-stress RNA-Seq datasets, and 937 samples. All samples are assigned to 133 stress-specific subsets, which are constructed into 254 subset pairs, a comparison between selected two subsets, for stress-specific differentially expressed transcript identification. CONCLUSIONS: PSRN is an open resource for intuitive data exploration, providing expression profiles of coding-transcript/lncRNA and identifying which transcripts are differentially expressed between different stress-specific subsets, in order to support researchers generating new biological insights and hypotheses in molecular breeding or evolution. PSRN is freely available at http://syslab5.nchu.edu.tw/PSRN .

Biclustering of transcriptome sequencing data reveals human tissue-specific circular RNAs.

BACKGROUND: Emerging evidence has been experimentally confirmed the tissue-specific expression of circRNAs (circRNAs). Global identification of human tissue-specific circRNAs is crucial for the functionality study, which facilitates the discovery of circRNAs for potential diagnostic biomarkers. RESULTS: In this study, circRNA back-splicing junctions were identified from 465 publicly available transcriptome sequencing samples. The number of reads aligned to these identified junctions was normalized with the read length and sequence depth for each sample. We generated 66 models representing enriched circRNAs among human tissue transcriptome through biclustering algorithm. The result provides thousands of newly identified human tissue-specific circRNAs. CONCLUSIONS: This result suggests that expression of circRNAs is not prompted by random splicing error but serving molecular functional roles. We also identified circRNAs enriched within circulating system, which, along with identified tissue-specific circRNAs, can serve as potential diagnostic biomarkers.