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Background and rationale Idiopathic pulmonary fibrosis is a critical disease with a poor prognosis. Although different studies have been conducted for the treatment of idiopathic pulmonary fibrosis, limited treatments are available. Jin-shui Huan-xian granule (JHG), which is a Chinese medicine herbal compound, has shown promising efficacy in reducing frequencies of acute exacerbations, improving exercise capacity the quality of life of patients with idiopathic pulmonary fibrosis. This study is to evaluate the efficacy and safety of JHG for IPF. Subjects and methods This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 312 idiopathic pulmonary fibrosis patients will be enrolled and randomly allocated to one of the two groups with 1:1. After a 2-week washout period, 52-week treatment will also be performed for all the patients. Patients in the experimental group and the control group will be given JHG and JHG placebo, respectively. Outcome measures including acute exacerbations, pulmonary function, dyspnea, exercise capacity, and quality of life will be evaluated in this study. Discussion Based on our previous study, it is hypothesized that JHG will reduce acute exacerbations; improve exercise capacity, pulmonary function, and quality of life; and delay the disease progression-free. High-level evidence-based support for TCM in IPF will also be obtained in this study. Trial registration ClinicalTrials.gov NCT04187690. Register on December 11, 2019

The automatic generation algorithm of optical coherence tomography (OCT) images based on generative adversarial networks (GAN) can generate a large number of simulation images by a relatively small number of real images, which can effectively improve the classification performance.We proposed an automatic generation algorithm for retinal OCT images based on GAN to alleviate the problem of insufficient images with high quality in deep learning, and put the diagnosis algorithm toward clinical application.We designed a generation network based on GAN and trained the network with a data set constructed by 2014_BOE_Srinivasan and OCT2017 to acquire three models. Then, we generated a large number of images by the three models to augment age-related macular degeneration (AMD), diabetic macular edema (DME), and normal images. We evaluated the generated images by subjective visual observation, Fréchet inception distance (FID) scores, and a classification experiment.Visual observation shows that the generated images have clear and similar features compared with the real images. Also, the lesion regions containing similar features in the real image and the generated image are randomly distributed in the image field of view. When the FID scores of the three types of generated images are lowest, three local optimal models are obtained for AMD, DME, and normal images, indicating the generated images have high quality and diversity. Moreover, the classification experiment results show that the model performance trained with the mixed images is better than that of the model trained with real images, in which the accuracy, sensitivity, and specificity are improved by 5.56%, 8.89%, and 2.22%. In addition, compared with the generation method based on variational auto-encoder (VAE), the method improved the accuracy, sensitivity, and specificity by 1.97%, 2.97%, and 0.99%, for the same test set.The results show that our method can augment the three kinds of OCT images, not only effectively alleviating the problem of insufficient images with high quality but also improving the diagnosis performance.

Nanorobots hold great promise for integrated drug delivery systems that are responsive to molecular triggers. Herein, we successfully developed an automatic smart bionanorobot that has transport capability and recognizes and removes zinc ions from poisoned cells based on nanoscale polyhedral oligomeric silsesquioxane molecules. This intelligent bionanorobot can easily move inside and outside the cell and find zinc ions owing to its highly selective recognition to zinc ions and high cell permeability, especially the well-combined high penetration and strong binding energy. More importantly, it was also found that this intelligent bionanorobot can restore round HeLa cells to a normal fusiform cell morphology following high-concentration zinc treatment and does not interfere with cell proliferation and division. It was also shown by

Purpose Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an essential occurrence in COPD management and is the leading cause of morbidity and mortality. Chinese herbal medicine is widely used in the treatment of AECOPD, but high quality randomized controlled trials are limited. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine as adjuvant therapy for patients with AECOPD. Methods This was a randomized, double-blind, placebo-controlled study of 378 participants from eight centers in China. Participants were randomly assigned to receive 10 g of Chinese herbal medicine (according to the type of Traditional Chinese medicine syndrome: Sanhanhuayin, Qingrehuatan, or Zaoshihuatan granules) or placebo, two times per day, for 14 days, in addition to conventional medicine. Participants were followed up for 84 days after the treatment. The primary end point was the COPD assessment test (CAT) score. Secondary end points included the Modified British Medical Research Council (mMRC) questionnaire and the COPD patient-reported outcome scale (COPD-PRO). We also assessed treatment failure and treatment success rate, length of hospitalization, number of patients with acute exacerbations, number of patients readmitted due to AECOPD, and number of deaths and intubation. Results The between-group difference in the change from baseline for CAT on day 14 (end of treatment) was -2.11 (95% confidence interval [CI], -3.198 to -1.050; P

Background Peroxiredoxin 1 (PRDX1) has been identified as a dual regulator of tumorigenesis. However, its expression, clinical significance, and biological function in nasopharyngeal carcinoma (NPC) remain unknown. This study aimed to explore the role and underlying mechanisms of PRDX1 in NPC. Materials and methods The expression of PRDX1 in NPC tissues was evaluated by immunohistochemistry, and the relationships between the expression of PRDX1 and clinical features and prognosis of NPC patients were analyzed. The effects of PRDX1 on NPC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were examined. A tumor-bearing model of nude mouse was established to verify the function of PRDX1 in vivo. Results PRDX1 expression level was negatively associated with recurrence and metastasis of NPC. PRDX1 knockdown promoted NPC cell proliferation, migration, invasion and EMT in vitro, and enhanced tumor growth in vivo, while PRDX1 overexpression had opposite effects. Furthermore, transcriptome analysis showed that PRDX1 inhibited the activation of PI3K/AKT/TRAF1 signaling in NPC cells. Conclusion PRDX1 inhibits NPC by inhibiting the activation of PI3K/AKT/TRAF1 signaling. PRDX1 is a tumor suppressor in human NPC and may be a prognostic biomarker for NPC patients.

To evaluate the effectiveness and safety of Qingjin Yiqi granules (QJYQ) on post-COVID-19 condition (PCC).Patients who met the inclusion criteria were randomly assigned to two groups, the QJYQ group received QJYQ combined with standard rehabilitation treatments (SRTs) and the control group only received SRTs. The treatment course was 14 days. The primary outcomes were modified Medical Research Council (mMRC) scale and Borg scale, while the secondary outcomes included symptoms score and 6-minute walking distance (6MWD). The safety outcome was the incidence of adverse events.A total of 388 patients with PCC were enrolled and randomly assigned to the QJYQ group (n = 194) and the control group (n = 194). Compared to the controls, the mMRC scale was improved in the QJYQ group, which was better than that of the control group [β (95%CI): -0.626 (-1.101, -0.151), p = 0.010]. A significant improvement in Borg scale was also observed in the QJYQ group compared to the control group [β (95%CI): -0.395(-0.744, -0.046), p = 0.026]. There was no statistically significant difference in symptoms score and 6MWD between the two groups (p = 0.293, p = 0.724). No treatment-related adverse events were observed in either group.QJYQ can bring benefits to patients with PCC, mainly in the improvement of breathlessness and fatigue.

Background The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. Purpose We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. Study design Living evidence-based guideline. Methods This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. Results The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. Conclusion This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

Mycobacterium tuberculosis, the pathogen of tuberculosis (TB), can survive in host macrophages and induce macrophages to M2 phenotype might result in latent MTB infection. During the latent phase, the expression of MTB heat-shock protein 16.3 (Hsp16.3) is markedly increased among most of bacterial proteins, but the role of Hsp16.3 in macrophage M2 polarization is not clear. In this work, we found that macrophages incubated with 100 ng/ml MTB Hsp16.3 increased the production of Arg-1, IL-10, TGF-beta, and CD206. These results showed that MTB Hsp16.3 may induce macrophage M2 phenotype. And the interaction of Hsp16.3 with macrophages was found to depend on chemokine receptors CCRL2 and CX3CR1. Additionally, we used overexpression and silencing techniques to further verify the effect of CCRL2 and CX3CR1 on MTB Hsp16.3-induced M2 polarization macrophages. Furthermore, we explored the downstream signaling molecules of CCRL2 and CX3CR1 and we found MTB Hsp16.3 altered the signal transduction of the AKT/ERK/p38-MAPK. Taken together, this study provides evidence that MTB Hsp16.3 promotes macrophages to M2 phenotype and explores its underlying mechanism.

Pseudopodium enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, was recently implicated in cancer pathogenesis. However, its functional role in colorectal cancer (CRC) is not well known. Herein, we demonstrated that PEAK1 was frequently downregulated in CRC and significantly associated with tumor size, differentiation status, metastasis, and clinical stage. PEAK1 overexpression suppressed CRC cell growth, invasion, and metastasis in vitro and in vivo, whereas knockout had the opposite effects. Further evaluation revealed that PEAK1 expression was positively correlated with protein phosphatase 1 regulatory subunit 12B (PPP1R12B) in CRC cell lines and clinical tissues, and this protein was found to suppress activation of the Grb2/PI3K/Akt pathway. Moreover, PPP1R12B knockdown markedly abrogated PEAK1-mediated tumor suppressive effects, whereas its upregulation recapitulated the effects of PEAK1 knockout on cell behaviours and the activation of signalling. Mechanistically, PI3K and Akt inhibitors reversed impaired the effect of PEAK1 function on cell proliferation, migration, and invasion. Our results provide compelling evidence that the PEAK1-PPP1R12B axis inhibits colorectal tumorigenesis and metastasis through deactivation of the Grb2/PI3K/Akt pathway, which might provide a novel therapeutic strategy for CRC treatment.

Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.

Chemotherapy mostly functions as a carrier for direct drug delivery to the tumor, which may induce secondary damage to healthy tissue cells around the tumor. To avoid this side effect, using multifunctional drugs with high cell permeability during chemotherapy is crucial to achieve significant antitumor efficacy. In this study, polyhedral oligomeric silsesquioxane-based multifunctional organic-inorganic hybrid molecules with potential for recognition, imaging, and treatment were designed and successfully synthesized through a facile and efficient one-pot reaction process. The structure and properties of the synthesized multifunctional molecules were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, mass spectrometry, fluorescence spectroscopy, cytotoxicity assay, surface tension testing, cell compatibility testing, hematoxylin and eosin staining, as well as in vivo and in vitro studies. The results demonstrated that these multifunctional molecules can be effectively used for delivering precisely-targeted imaging and therapeutic agents and exhibited considerable cell permeability. The excellent synergy between high permeability and precise targeting results in multifunctional molecules with superior diagnostic performance.

In this study, we describe a simple method to produce signals which can reveal the cross-sectional information of samples in an optical coherence tomography (OCT) system. Instead of using the spectrometer and the Fourier transformation calculation in the conventional spectrum domain (SD) OCT system, we use a Mach-Zehnder interferometer structure of the spatial heterodyne spectrometer. In a spatial heterodyne spectrometer, because each position on the photodetector array could be mapped to a specific optical path difference, the spectral density distribution could be retrieved with Fourier transformation. And in an SD-OCT system, cross-section signals are obtained by conducting Fourier transformation to the spectrum signals. Therefore, in our OCT system, the spatial signals captured by the photodetector array is related to the cross-sectional signals obtained in an SD-OCT system. The theoretical study and the numerical simulation demonstrate that by applying our method in an OCT system, the heterodyne spectrometer structure could generate a symmetrical pattern composed of fringes with high spatial frequency. Then the photodetector array captures the pattern to generate a spatial signal. The spatial ordinate of this signal is linearly related to the optical depth in sample, while the amplitude of the signal intensity variation is linearly related to the intensity of coherent backscattered light in the sample. The imaging depth is theoretically unlimited. Also, because of the high spatial frequency of the signal, we further adjust the inclination angle in the heterodyne spectrometer structure to visualize the signal.

Spectral analysis is an important method for noninvasive blood glucose measurement. Presently, Fourier-transform spectroscopy is a well-established technique that provides highly resolved spectral measurements in the infrared, visible and ultraviolet ranges. In this study, we proposed a novel method for obtaining linear spectra based on regular Spatial Heterodyne Spectrometers. In particular, we wanted to use a fluorescent dye-coated screen and a Fourier lens to directly obtain uniform K-space spectra. In the system, the up-conversion luminescent material on the screen is hoped to absorb coherent incident light and emit light of a specific wavelength that maintains the coherence. According to our calculation, the photodetector array receives the Fourier image pattern on the screen and can directly obtain the spectrum of the measured substance, therefore the scientists can directly observe the spectrum of the test sample. Furthermore, we replace the fluorescent dye-coated screen by an infrared laser detector card, which is commonly used in laboratories, to primary verify the feasibility of the method. Up-conversion luminescent materials that are widely used in the fields of analytical chemistry, biomedicine, and life sciences, have very good application prospects in biological imaging, photodynamic therapy, solar cells, flexible fluorescent films and sensing.

We present an automatic classification algorithm for retinal optical coherence tomography (OCT) images based on convolution neural network (CNN). This algorithm inherently contains feature extraction and classification, thus avoiding the design feature extractor manually. Firstly, we processed the OCT images to focus on and determine the pathological area of the retinal OCT images, and to speed up the training of the network. Then we input the original images to crop them, which can effectively prevent the noise introduced in the processes of image processing and changing the pixels in the original image. Secondly, we augmented the OCT images in the source data set to obtain sufficient images, and to alleviate the impact of a relatively small number of target classification images on the model accuracy and generalization ability. Our method was introduced the random translation in image cropping and horizontal flipped to augment the OCT images. Then we applied two methods to build two data sets used to train the network, and we divided each of the data sets into a training set and a validation set. Next, we designed an efficient classification network and trained it with the two training sets respectively, to acquire the two models that can classify OCT images. The results indicate that the network trained by the augmented data can classify images more effectively. In our classification algorithm, the accuracy, the sensitivity and the specificity are 93.43%, 91.38%, and 95.88%, respectively.

To evaluate the effects of Qizhukangxian granules (QG) on idiopathic pulmonary fibrosis (IPF).This is a randomized, double blind, placebo-controlled and multicenter clinical pilot trial. Six medical centers in Tianjin, China, participated in the study. A total of 120 IPF patients were enrolled and randomized into two groups, with 60 patients in each group. The treatment group was treated with QG, while the control group received a Qizhukangxian placebo. The pharmacological treatment lasted for 48 weeks from the enrollment date. The indexes of patients were recorded on the admission day and at the end of the 24th and 48th weeks. Data were analyzed to study the effects of QG; forced vital capacity, change in forced vital capacity and maximal 6-min walk test (6MWT) distance were the primary endpoints. Secondary endpoints were percentage of patients with episodes of acute exacerbation of IPF, pulmonary function, changes in pulse oxygen saturation during the 6MWT, dyspnea score, St. George's respiratory questionnaire score, arterial blood gas analyses and the total Traditional Chinese Medicine symptom pattern score.After 24 weeks of treatment, QG showed greater efficacy than the placebo in certain parameters, including the dyspnea score, Traditional Chinese Medicine symptom pattern score and some indicators in the St. George's respiratory questionnaire score. Analysis of the indexes obtained from all patients at the end of the 48th week showed that the therapeutic effects in the treatment group were significantly better than those in the control group because remarkable differences were observed in most of the primary and secondary endpoints between the two groups, except for the maximal distance of the 6MWT and arterial blood gas analyses. No adverse reaction was observed in either group during the 48-week trial treatment period.QG could effectively treat IPF patients by ameliorating pulmonary function, improving the quality of life and lowering the percentage of acute exacerbations.

Background: Regarding the outbreak of highly contagious the 2019 Novel Coronavirus (2019-nCoV) in various countries and regions, data have been needed on the early chest CT images and clinical characteristics of the affected patients. Objectives: To explore the early clinical and computed tomography (CT) characteristics of the 2019 Novel Coronavirus Disease (COVID-19) patients to improve the diagnostic level of this contagious respiratory disease. Methods: An analysis retrospectively was implemented on the radiological features and clinical characteristics of 12 patients with COVID-19 who had undergone chest CT scanning in the designated hospital from Jan 23, 2020, to Feb 18, 2020. The clinical data on general information, epidemiological, cardinal symptoms, blood test, and CT imaging characteristics were obtained. Results: According to the relevant diagnostic criteria, the patients were divided into two groups: mild (2 cases), and ordinary type (10 cases). The main symptoms of 2019-nCoV pneumonia were fever (9/12) and cough (8/12) with or without respiratory and other systemic symptoms. The blood test of the patients showed that most of the white blood cell count was normal (10/12), decreased lymphocyte count (6/12), and increased hypersensitive C reactive protein (hs-CRP) (5/12). In the early stage of COVID-19, the chest CT images showed patchy mixed ground-glass opacity (GGO) (8/12), mainly distributed in the periphery and posterior part of both lungs. The internal density of image lesion area was uneven, and lesions primarily manifested as “crazy-paving pattern” (8/12), with grid-like, interlobular septal thickening, thickened bronchovascular bundle and air bronchus sign and multiple fibrosis. A few cases showed pulmonary atelectasis (1/12), bilateral pleural effusion (1/12), no mediastinal or bilateral hilar lymph node enlargement. Conclusions: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. The chest CT images may be helpful for the early detection of novel coronavirus pneumonia.

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

IntroductionClinical management of asthma remains a public challenge. Despite standard treatment with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), asthma remains uncontrolled in a substantial number of chronic asthma patients who risk reduced lung function and severe exacerbations. Azithromycin could have add-on effects for these patients. This study is proposed to systematically evaluate the efficacy of azithromycin as an add-on treatment for adults with persistent uncontrolled symptomatic asthma.Methods and analysisTwo reviewers will perform a comprehensive search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese electronic databases including China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), WanFang Data and VIP Database from inception to May 2019. Only randomised controlled trials will be included. There is no restriction on language or publication status. Combined oral azithromycin and an ICS or/and a LABA will be compared with standard treatment alone or with a placebo. The primary outcomes are the number or frequency of asthma exacerbations, changes in asthma symptoms and lung function. Secondary outcomes include the number or frequency of inhalations of beta-agonists with or without corticosteroids for rescue use, eosinophil counts in blood or sputum, adverse events and others. A meta-analysis will be attempted to provide an estimate of the pooled treatment effect. Otherwise, qualitative descriptions of individual studies will be given.Ethics and disseminationEthical approval is not required because no primary data will be collected. Study findings will be presented at scientific conferences or published in a peer-reviewed journal.PROSPERO registration numberCRD42019117272.

Emerging evidence has indicated that transforming growth factor-beta 1 (TGF-β1) induces the epithelial–mesenchymal transition (EMT) in cancer cells, thus promoting their motility and invasiveness. Quercetin, a member of the polyphenolic flavonoid family, has been reported to display anticancer activity against a broad range of cancer cell types. Indeed, numerous studies have shown the cancer preventive effects and molecular mechanisms of quercetin in vitro using diverse cell model systems. However, the potential effect of quercetin on EMT remains unclear. In this study, we identified a unique function of quercetin in inhibiting the EMT process induced by TGF-β1. In particular, quercetin rescued the morphological changes and EMT-like phenotypes in TGF-β1-activated SW480 cells, and this inhibition of TGF-β1-induced EMT was mediated via the suppression of Twist1 expression. In addition, quercetin strongly suppressed TGF-β1-induced invasion of SW480 cells. Thus, quercetin may be considered a novel therapeutic agent for the treatment of patients with refractory cancer and for the prevention of the metastatic cascade initiated by EMT.

To improve the water-solubility of heavy-metal sensing materials, a modified fluorescein-based derivative, acryloyl fluorescein hydrazine (ACFH), was designed and developed by incorporating a non-hydrogen-bonding group into the conjugated molecule for weakening intermolecular hydrogen-bonding interactions. In neutral water environments, ACFH presented a fluorescence-enhancement performance at λmax=512nm in the presence of Hg2+, which could be visualized by naked-eyes. Under the optimized conditions, the linear range of Hg2+ detection was 1.0-100×10-9molL-1 with a correlation coefficient of 0.9992 and a detection limit of 0.86×10-9molL-1. The recognition mechanism was confirmed to be a stable and irreversible 1:1 five-member ring complex between ACFH and Hg2+ with a coordination constant of 3.36×109. ACFH would possess a potential application in detecting Hg2+ for biological assay with low cytotoxicity.

Background Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves as a critical signaling amplifier downstream of tyrosine kinase receptors. Our previous study has shown that Gab2 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of Gab2 in CRC growth and angiogenesis remains unclear. Methods The expression of vascular endothelial growth factor (VEGF) in different colorectal tissues was detected by immunohistochemistry and qRT-PCR to evaluate its correlation with Gab2. Lentiviral vectors bearing Gab2 gene and its small interfering RNAs were constructed and transfected into CRC cell lines. The effects of Gab2 on the cell proliferation in vitro and tumorigenesis in vivo, were examined via CCK‑8 assay, colony formation assay as well as tumorigenicity assay respectively. Moreover, to assess its potential role in tumor growth and angiogenesis, the expression of Ki67, CD34 and vascular endothelial growth factor receptor-2 (VEGFR2) were detected by immunohistochemistry in CRC cells tumors. Finally, we evaluated the impact of Gab2 on the expression of c-Myc and VEGF, and the probable effect of mechanistic targeted extracellular signal-regulated kinase (ERK) pathway in suppressing tumor growth and angiogenesis. Results Up-regulation of Gab2 expression was found to be positively correlated with VEGF in CRC tissues. Exogenous expression of Gab2 obviously promoted, whereas silencing of Gab2 inhibited, proliferation and clone formation of human CRC cells in vitro. Of note, Gab2 enhanced tumorigenesis and tumor growth in mouse xenografts with high Ki67 expression, and led to an increased vessel density with strong CD34 and VEGFR2 activity. In addition, elevated Gab2 expression obviously up-regulated the expression of VEGF, and stimulated the activation of its downstream genes, ERK1/2 and c-Myc in CRC cells. Instead, down-regulated Gab2 expression significantly reduced the levels of VEGF, and inhibited the transduction of ERK/c-Myc pathway. Finally, we revealed that mechanistic target of mitogen-activated protein kinase (MEK) could attenuate Gab2-induced tumor growth and angiogenesis via altering VEGF and c-Myc levels. Conclusions The results from our study suggest that Gab2 promotes intestinal tumor growth and angiogenesis through upregulation of VEGF expression mediated by the MEK/ERK/c-Myc pathway. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0524-2) contains supplementary material, which is available to authorized users.

IntroductionAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) brings a serious impact on patients’ quality of life, and has extremely high morbidity and mortality worldwide. Although there are many therapies being developed to alleviate symptoms and reduce mortality, a few studies have supported which treatment method is the best. Traditional Chinese medicine (TCM) has shown good potential in the prevention and treatment of AECOPD, especially in terms of supplementation and reduction of dosage and adverse effect of Western medicine. The purpose of this study is to compare the effectiveness of combination of TCM and Western medicine with conventional therapy alone for AECOPD, and to ensure whether the combined therapy may reduce the use of systemic glucocorticoid in AECOPD without influencing efficacy.Methods and analysisA multicentre, randomised, double-blind, placebo-controlled study was conducted to enrol a total of 360 eligible patients who will be randomised into integrated Chinese and Western medicine group A, B and Western standard Medicine group C. After 5 days of intervention and 1 month of follow-up, the efficacy and safety of Xin Jia Xuan Bai Cheng Qi Decoction in patients with AECOPD will be observed. The results of evaluation indicators include: clinical symptoms, biochemical indicators such as blood gas analysis, inflammatory markers, hospitalisation time, TCM syndrome evaluation, biological indicators such as airway, intestinal flora sequencing.Ethics and disseminationThis trail has been approved by the Ethics Committee of China-Japan Friendship Hospital. The results will be disseminated in international peer-reviewed journals and be presented in academic conferences. The results will also be disseminated to patients by telephone, inquiring on patient’s poststudy health status during the follow-up.Trial registration numberChiCTR1800016915

Diabetes has been a serious problem that poses threat to people's health all around the world. It is still a challenge for us to detect blood glucose concentration continuously and non-invasively. In this research, we developed a free-space spectrum domain optical coherence tomography (SD-OCT) system for non-invasive blood glucose detection which possessed advantages of easy construction, analyzation and control. In this system, a laser with center wavelength of 980nm was applied because of its low absorption in both glucose and water, which was suitable for OCT imaging. However, the laser with wavelength of 980nm was not used in the OCT with optic fiber type which was commercially designed for wavelengths of 830nm, 1310nm and 1550nm. By applying a dispersing prism, we could obtain higher resolution spectrum to acquire better OCT images and more accurate glucose concentration. The tomography function of this free-space SD-OCT system was proved to work by scanning onion sample. Pristella maxillaris is a kind of fish with transparent body structure and suitable size, thus we consider it to be an ideal animal for blood glucose measurement by optical methods. We cultivated pristella maxillaris, an ideal fish for this experiment, in glucose solutions with five different concentrations as samples to study glucose monitoring. The OCT signals of the five groups correlated respectively to the glucose concentrations. Therefore, our method provided the potential for measuring blood glucose concentration non-invasively.

Inositol polyphosphate 4-phosphatase type II (INPP4B), a lipid phosphatase, was identified as a negative regulator of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in several cancers. The expression and biological function of INPP4B in human colorectal cancer (CRC) are controversial, while the role and molecular mechanism of INPP4B in colorectal cancer stem-like cells (CR-CSLCs) remains unclear. Here, we observed that INPP4B expression was markedly decreased in primary non-metastatic CR-CSLCs and increased in highly metastatic CR-CSLCs compared with corresponding control non-CSLCs. INPP4B overexpression inhibited self-renewal, and chemoresistance of primary non-metastatic CR-CSLCs, but exerted the opposite roles in highly metastatic CR-CSLCs in vitro. Similarly, INPP4B knockdown had dual functions in the self-renewal and chemoresistance of different CR-CSLCs. In addition, we demonstrated that INPP4B overexpression suppressed the tumorigenicity of primary non-metastatic CR-CSLCs while induced the tumorigenicity of highly metastatic CR-CSLCs in nude mice. Furthermore, INPP4B was found to modulate the stemness of CR-CSLCs by regulating Sox2 and Nanog expression, which was dependent on PI3K/PTEN/Akt signaling. In conclusion, our results highlight an important role of INPP4B in the stemness of CR-CSLCs for the first time and emphasize INPP4B as a dual therapeutic target for suppressing primary cancer cell proliferation and for preventing metastasis in CRC patients.

The aim of this study was to identify the association polymorphism (rs11536889) in the 3'-untranslated region (3'-UTR) of Toll-like receptors 4 (TLR4) and the risk for ventilator-associated pneumonia (VAP). miRNA database online and luciferase assays were used to validate TLR4 as the target gene of miR-1236. Enzyme-linked immunosorbent assay analysis and western blot were used to analyze the level of TLR4 in different genotype groups. In the present study, miR-1236 was predicted to bind to the rs11536889 G allele rather than the rs11536889 C allele, which was further confirmed by the luciferase activity suppressed by a fragment of 3'-UTR containing the rs11536889 G allele induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6). Bronchial epithelial cells isolated from participants genotyped as GG, GC, and CC, with no remarkable difference in TLR4 messenger RNA (mRNA) levels were observed among these genotype groups. After stimulating by LPS, a TLR4 ligand, the CC-genotyped cells expressed higher levels of IL-8, IL-6, and tumor necrosis factor alpha (TNF-α) on their surfaces than cells with the other genotypes. Finally, the western blot analysis results showed that the expression level of IL-8, IL-6, and TNF-α protein was much higher in the CC group than the GC and GG groups subsequent to stimulation by LPS, and the IL-8, IL-6, and TNF-α protein levels in the GC were grouped much lower compared with the GG group. These findings indicated the regulatory association of miR-1236 with TLR4 and the abnormal expression of TLR4 caused by the presence of rs11536889 in the 3'-UTR of mRNA, which interfere with its interaction with the miR-1236, contributing to the risk of VAP.

2-(4-((4-Chloro-6-((3',6'-dihydroxy-3-oxospiro [isoindoline-1,9'-xanthen]-2-yl)amino)-1,3,5-triazin-2-yl)amino)benzoyl)-N-phenylhydrazine-1-carbothioamide (PCFH) is prepared for the detection of Hg2+ by hydrogen-induced emission (HIE). In the presence of blood serum, PCFH has a strong fluorescence response to Hg2+ in ethanol/H2O (90/10, v/v), while the fluorescence with other metal ions, including Cu2+, is much weaker. PCFH coordinates better with Hg2+ than Cu2+, which gives rise to specificity of detection. Through spectroscopic techniques and molecular dynamics simulations, the mechanism of HIE reveals that the interactions between polar bonds of PCFH and protein in blood serum via hydrogen bonding can efficiently enhance the specificity and sensitivity of detection. As the results of the interactions, the free rotation of two plenary structures of PCFH linked by C C bonds is restricted, which leads to increased planarity, and the protein destroys the coordination between Cu2+ and PCFH. The development of cells under Hg2+ pollution is monitored, and the concentrations of Hg2+ in deformed and dead cells are 0.47 μM and 0.88 μM respectively. The HIE effects found here will promote new ideas in the design of new types of fluorescence probes for Hg2+ and other metal ions.

To improve the water-solubility of heavy-metal sensing materials, a modified fluorescein-based derivative, acryloyl fluorescein hydrazine (ACFH), was designed and developed by incorporating a non-hydrogen-bonding group into the conjugated molecule for weakening intermolecular hydrogen-bonding interactions. In neutral water environments, ACFH presented a fluorescence-enhancement performance at λ

Objective To study the therapeutic effect Bufei granule, which is a traditional Chinese drug that can enhance the immune function of the lung, on patients with stable chronic obstructive pulmonary disease (COPD). Methods This is a randomized, double blinded, placebo-controlled, and multicenter clinical study. Three medical centers in Tianjin, China, participated in the trial. A total of 140 patients with stable COPD were enrolled and randomized into two groups, with 70 patients in each. The treatment group was treated with Bufei granule, while the control group received Bufei placebo. The pharmacological treatment lasted for 12 weeks from the date of enrollment. Then, the indexes of patients were observed. Data were analyzed to study the effect of Bufei granule, with the frequency of acute exacerbation as the primary outcome. Traditional Chinese Medicine syndromes, Modified British Medical Research Council dyspnea scale score, St. George's respiratory questionnaire scores, pulmonary function, and serum inflammatory marker levels [including interleukin-6 (IL-6), interleukin-8, tumor necrosis factor-α, and transformation growth factor-β1] were the secondary outcomes. Results During the 12-week treatment, treatment and control groups had no adverse reactions. The analysis of the indexes obtained from all patients showed that the therapeutic effect in the treatment group was significantly better than that in the control group because most of the similar probabilities of primary and secondary outcomes were less than 0.05, except for the level of IL-6. Conclusions Bufei granule can treat patients with stable COPD by lowering the frequency of acute exacerbation, improving the quality of life, and alleviating the severity of inflammation.

Peroxiredoxin 2 (Prdx2) is a member of the peroxiredoxin family, which is responsible for neutralizing reactive oxygen species. Prdx2 has been found to be ele- vated in several human cancer cells and tissues, including colorectal cancer (CRC), and it influences diverse cellular processes involving cells' survival, proliferation, and apoptosis, which suggests a possible role for Prdx2 in the maintenance of cancer cell. However, the mechanism by which Prdx2 modulates CRC cells' survival is unknown. The current study aimed to determine the effect of elevated Prdx2 on CRC cells and to further understand the under- lying mechanisms. The results of this study showed that Prdx2 was upregulated in CRC tissues compared with the matched noncancer colorectal mucosa tissues and that Prdx2 expression was positively associated with tumor metastasis and the TNM stage. In the LoVo CRC cell line, Prdx2 was upregulated at both the RNA and protein levels compared with the normal FHC colorectal mucosa cell line. In addition, the LoVo CRC cell line was significantly more resistant to hydrogen peroxide (H2O2)-induced apoptosis because of a failure to activate pro-apoptotic pathways in contrast to Prdx2 knockdown cells. Suppres- sion of Prdx2 using a lentiviral vector-mediated Prdx2- specific shRNA in the LoVo cell line restored H2O2 sen- sitivity. Our results suggested that Prdx2 has an essential role in regulating oxidation-induced apoptosis in CRC cells. Prdx2 may have potential as a therapeutic target in CRC.

Background Grb2-associated binder 2 (Gab2), a scaffolding adaptor protein, has recently been implicated in cancer progression. However, the role of Gab2 in the progression and metastasis of colorectal cancer (CRC) remains unclear. Methods Gab2 expression was assessed in CRC patient specimens as well as in CRC cell lines. Recombinant lentivirus vector containing Gab2 gene and its small interfering RNAs were constructed and introduced into CRC cells. Cell migration and invasion ability were evaluated by transwell assays in vitro, and in vivo metastasis was performed on nude mice model. Moreover, the expression of Gab2 and epithelial-to-mesenchymal transition (EMT)-associated proteins (E-cadherin and vimentin) were assessed by western blot and qRT-PCR in CRC cells to evaluate the correlation between Gab2 and EMT. Finally, we evaluated the impact of Gab2 on the activation of its downstream signaling effectors, and furthermore the effects of these pathways on Gab2 induced-EMT were also detected. Results We confirmed that increased Gab2 expression correlated with higher tumor node metastasis stage and highly invasive CRC cell lines. Ectopic expression of Gab2 promoted metastasis of CRC cells, whereas silencing of Gab2 resulted in inhibited metastasis both in vitro and in vivo. Overexpression of Gab2 in CRC cells induced EMT, whereas knockdown of Gab2 had the opposite effect. Furthermore, upregulation of Gab2 expression obviously stimulated the activation of extracellular signal-regulated kinase-1/2 (ERK1/2), and increased the expression of matrix metalloproteinase-7 (MMP7) and matrix metalloproteinase-9 (MMP9) in CRC cells. Conversely, downregulation of Gab2 expression significantly decreased the activation of ERK1/2, and inhibited MMP7 and MMP9 expression. U0126, an inhibitor of mitogen-activated protein kinase (MEK), can reverse the effects of Gab2 on EMT. Conclusions Our work highlights that Gab2 induces EMT through the MEK/ERK/MMP pathway, which in turn promotes intestinal tumor metastasis. Electronic supplementary material The online version of this article (doi:10.1186/s13046-015-0280-0) contains supplementary material, which is available to authorized users.

Clinicopathologic factors and Gab2 expression in 35 CRC patients. (DOCX 22 kb)

Aiming at the difficulty in X ray diagnosis for the sacroiliac joint's subluxation, the sacroiliac joint images for a patient's physiological state and pathological state are analyzed in this paper. We find that the image of the iliac pro-up shift 7mm is similar to that of the pelvic rotation 10o around the Y axis, and the image of the iliac external rotation 5o is similar to that of the pelvis rotation 5o around the Z axis. These results may easily lead to a massage doctor's misdiagnosis or leak-diagnosis.

Carcinoma cells hijack the epithelial-mesenchymal transition (EMT) for tumor dissemination. Paired-related homeobox 1 (PRRX1) has been identified as a new EMT inducer. However, the function of PRRX1 in gastric cancer has not been elucidated. In this study, we observed that PRRX1 expression levels were upregulated and positively correlated with metastasis and EMT markers in human gastric cancer specimens. PRRX1 overexpression had distinct effects on the cell morphology, proliferation, migration and invasion of BGC823 and SGC7901 gastric cancer cells both in vitro and in xenografts. PRRX1 overexpression resulted in the regulation of the EMT molecular markers N-cadherin, E-cadherin and vimentin as well as the levels of intranuclear β-catenin and the Wnt/β-catenin target c-Myc. Furthermore, the inhibition of the Wnt/β-catenin pathway by XAV939 offset the effects of PRRX1 overexpression. These findings demonstrate that PRRX1 promotes EMT in gastric cancer cells through the activation of Wnt/β-catenin signaling and that PRRX1 upregulation is closely correlated with gastric cancer metastasis.