To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial

Background: Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE). Methods/Design This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year. Discussion We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung function parameters, and total scores judged by the St George’s respiratory questionnaire, Leicester cough questionnaire, and inflammatory index. We hope that this study will provide new information on the preventive effects of OM-85 on bronchiectasis exacerbations and will address a knowledge gap for this understudied disease. Trial registration This study is registered at http://www.clinicaltrials.gov (identifier NCT01968421) on 19 October 2013

The Role of CXCR3 in the Induction of Primary Biliary Cirrhosis

Objective. Investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC) in an autoimmune cholangitis animal model. Methods. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 weeks. PBC model was confirmed by liver function, serum autoantibodies and liver biopsy. Lymphocytes subsets in liver and spleen and CXCL10 serum level were tested by flow cytometry and ELISA. Liver specimens were collected to evaluate the differences in pathology between WT and CXCR3−/− mice. Results. Antimitochondrial antibody was detected in all PBC model. Numbers of infiltrates were detected in the portal areas 8 weeks after poly I:C injection, which progressed up to 24 weeks. Compared to control mice, CXCL10 serum level increased in PBC mice and the proportion of CXCR3+ cells increased in the intrahepatic infiltrates of PBC mice, chiefly on CD8+ cells, whereas the expression of CXCR3 on CD3+ and CD8+ splenocytes decreased in PBC model. Compared with WT mice, CXCR3−/− mice developed delayed and milder progression of cellular inflammation. Conculsions. CXCR3 might contribute to the development of PBC in murine model. Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development

Exploiting modality-invariant feature for robust multimodal emotion recognition with missing modalities

Multimodal emotion recognition leverages complementary information across modalities to gain performance. However, we cannot guarantee that the data of all modalities are always present in practice. In the studies to predict the missing data across modalities, the inherent difference between heterogeneous modalities, namely the modality gap, presents a challenge. To address this, we propose to use invariant features for a missing modality imagination network (IF-MMIN) which includes two novel mechanisms: 1) an invariant feature learning strategy that is based on the central moment discrepancy (CMD) distance under the full-modality scenario; 2) an invariant feature based imagination module (IF-IM) to alleviate the modality gap during the missing modalities prediction, thus improving the robustness of multimodal joint representation. Comprehensive experiments on the benchmark dataset IEMOCAP demonstrate that the proposed model outperforms all baselines and invariantly improves the overall emotion recognition performance under uncertain missing-modality conditions. We release the code at: https://github.com/ZhuoYulang/IF-MMIN.Comment: 5 pages, 3 figures, 1 table. Submitted to ICASSP 2023. We release the code at: https://github.com/ZhuoYulang/IF-MMI

Papel de la bahía de Jiaozhou como una fuente/depósito de CO2 durante un ciclo estacional

The seasonal evolution of dissolved inorganic carbon (DIC) and CO2 air-sea fluxes in the Jiaozhou Bay was investigated by means of a data set from four cruises covering a seasonal cycle during 2003 and 2004. The results revealed that DIC had no obvious seasonal variation, with an average concentration of 2035 µmol kg-1 C in surface water. However, the sea surface partial pressure of CO2 changed with the season. pCO2 was 695 µatm in July and 317 µatm in February. Using the gas exchange coefficient calculated with Wanninkhof’s model, it was concluded that the Jiaozhou Bay was a source of atmospheric CO2 in spring, summer, and autumn, whereas it was a sink in winter. The Jiaozhou Bay released 2.60 x 1011 mmol C to the atmosphere in spring, 6.18 x 1011 mmol C in summer, and 3.01 x 1011 mmol C in autumn, whereas it absorbed 5.32 x 1010 mmol C from the atmosphere in winter. A total of 1.13 x 1012 mmol C was released to the atmosphere over one year. The behaviour as a carbon source/sink obviously varied in the different regions of the Jiaozhou Bay. In February, the inner bay was a carbon sink, while the bay mouth and the outer bay were carbon sources. In June and July, the inner and outer bay were carbon sources, but the strength was different, increasing from the inner to the outer bay. In November, the inner bay was a carbon source, but the bay mouth was a carbon sink. The outer bay was a weaker CO2 source. These changes are controlled by many factors, the most important being temperature and phytoplankton. Water temperature in particular was the main factor controlling the carbon dioxide system and the behaviour of the Jiaozhou Bay as a carbon source/sink. The Jiaozhou Bay is a carbon dioxide source when the water temperature is higher than 6.6°C. Otherwise, it is a carbon sink. Phytoplankton is another controlling factor that may play an important role in behaviour as a carbon source or sink in regions where the source or sink nature is weaker.La evolución estacional del carbono inorgánico disuelto (DIC) y el intercambio de flujos de CO2 aire-mar en la bahía de Jiaozhou han sido investigados a partir de datos obtenidos en 4 campañas oceanográficas que cubren un ciclo estacional entre 2003 y 2004. Los resultados muestran que el DIC no presenta una clara variación estacional con una concentración promedio de 2035 μmol kg-1 C en el agua de superficie. No obstante la presión parcial de CO2 en el agua superficial cambiaba con la estación. La PCO2 era de 695 μatm en Julio y 317 μatm en febrero. Utilizando el coeficiente de intercambio de gases calculado con el modelo de Wanninkhof concluíamos que la bahía de Jiaozhou era una fuente de CO2 a la atmósfera en primavera, verano y otoño, mientras que era un depósito de CO2 en invierno. La bahía proporcionaba 2.60 × 1011 mmol C a la atmósfera en primavera, 6.18 × 1011 mmol C en verano, y 3.01 × 1011 mmol C in otoño, mientras absorbia 5.32 × 1010 mmol C desde la atmósfera en invierno. Un total de 1.13 × 1012 mmol C eran liberados a la atmósfera durante un año. El comportamiento como fuente/depósito de carbono, obviamente era diferente en las distintas regiones de la bahía de Jiaozhou. En Febrero, la parte interior de la bahía era un depósito para el carbono, mientras que la desembocadura y la parte exterior actuaba como fuente de carbono. En Junio y Julio, las partes interna y externa de la bahía eran fuentes de carbono, pero la intensidad era diferente, incrementando desde la parte interior a la exterior de la bahía. En Noviembre, la parte interior de la bahía era fuente de carbono, pero la desembocadura de la bahía se comportaba como depósito de carbono. El exterior de la bahía era una fuente poco importante de CO2. Estos cambios están controlados por muchos factores, siendo los mas importantes la temperatura y el fitoplancton. Especialmente, la temperatura del agua era el factor principal en el control del dióxido de carbono en el sistema y del comportamiento de la bahía de Jiaozhou como fuente/depósito de carbono. La bahía de Jiaozhou es una fuente de dióxido de carbono cuando la temperatura del agua es mas alta que 6.6ºC. Si no es así es un depósito de carbono. El fitoplancton es el otro factor de control que puede jugar un papel importante en el comportamiento como fuente o depósito de carbono en regiones donde el carácter de fuente o depósito es debil.

Colloidal toxic trace metals in urban riverine and estuarine waters of Yantai City, southern coast of North Yellow Sea

The environmental characteristics of colloidal toxic trace metals Cd, Cu and Pb in riverine and estuarine waters collected from two urban rivers of Yantai City in eastern China, the Guangdang and Xin'an Rivers, were investigated using a modified centrifugal ultrafiltration (CUF) method in conjunction with acid extraction and inductively coupled plasma mass spectrometry. The target metals in dissolved pool were divided into four CUF fractions, i.e. <1 kDa, 1-3 kDa, 3-10 kDa and 10 kDa-0.2 mu m, and the results showed that colloidal Cd, Cu and Pb were dominated by 1-10 kDa (1-3 and 3-10 kDa), 1-3 kDa and 10 kDa-0.2 lm fractions, respectively. The coagulation/flocculation of low-molecular-weight (1-10 kDa) colloidal Cd and Cu in the estuaries was obvious and strong, while the enrichment of dissolved Pb in the 10 kDa-0.2 lm fraction may be mainly related to its biogeochemical interactions with Fe-oxides, which is easy to occur in macromolecular colloids. In addition, the actual molecular weight cutoffs (MWCOs) of the three used CUF units with nominal MWCOs of 1, 3 and 10 kDa were determined to be 4.9, 8.5 and 33.9 kDa, respectively, indicating that membrane calibration is essential for explaining the actual fraction of dissolved trace metals and verifying the integrity of ultrafiltration membrane. Overall, the results in this study provide a further understanding of the heterogeneity in biogeochemical features, migration and fate of toxic trace metals in aquatic ecosystems, especially that of the river-sea mixing zone. (C) 2019 Elsevier B.V. All rights reserved

Fabrication and characterization of controlled release poly(D,Llactide-co-glycolide) millirods

Abstract: A compression-heat molding procedure was developed to fabricate poly(D,L-lactide-co-glycolide) (PLGA) controlled release drug delivery devices for the local treatment of tumors. The drug delivery devices were designed in the shape of a cylindrical millirod (1.6-mm diameter, 10-mm length), which allows them to be implanted by a modified 14-gauge tissue biopsy needle into tumor tissues via imageguided interventional procedures. In this study, the prototype trypan blue-containing PLGA millirods were fabricated under a compression pressure of 4.6 × 10 6 Pa and different fabrication temperatures for 2 h. The scanning electron microscopy results showed complete polymer annealing for millirods fabricated at 80 and 90°C, while the cross sections of the 60 and 70°C millirods showed incompletely annealed PLGA microspheres and trypan blue powders. The density, flexural modulus, and release properties of the PLGA millirods were also characterized and compared. The average values of the density and flexural modulus of the millirods increased with an increase in fabrication temperature. The flexural modulus values of most PLGA millirods were above 1 × 10 8 Pa, which provides sufficient stiffness for implantation within the tumor tissue. In addition, a ⌬c p method was developed to determine the loading density of trypan blue in the PLGA millirods by differential scanning calorimetry. Results from the ⌬c p measurement showed that trypan blue was homogeneously distributed in the millirod. Release studies in phosphate-buffered saline showed that the release rate decreased for the millirods fabricated at higher temperatures. The times for the release of 50% trypan blue were 5, 25, 25, and 25 h for millirods fabricated at 60, 70, 80, and 90°C, respectively. Millirods fabricated at 90°C had the most reproducible release profiles. The results from this study established compression-heat molding as an effective method to fabricate controlled release PLGA millirods with sufficient mechanical strength and reproducible release profiles for local cancer therapy

Vitamin D binding protein variants associate with asthma susceptibility in the Chinese han population

<p>Abstract</p> <p>Background</p> <p>Asthma is a genetically heterogeneous disease. Polymorphisms of genes encoding components of the vitamin D pathway have been reported to associate with the risk of asthma. We have previously demonstrated that vitamin D status was associated with lung function in Chinese asthma patients. In this study, we tested whether polymorphisms of genes encoding for vitamin D receptor (<it>VDR</it>), vitamin D 25-hydroxylase (<it>CYP2R1</it>) and vitamin D binding protein (<it>GC</it>) were associated with asthma in the Chinese Han population.</p> <p>Methods</p> <p>We sequenced all 8 exons of <it>VDR </it>and all 5 exons of <it>CYP2R1 </it>in a Chinese case-control cohort of asthma consisting of 467 cases and 288 unrelated healthy controls. Two mutations were identified in these regions. These variants were specified as rs2228570 in exon 2 of <it>VDR </it>and rs12794714 in exon 1 of <it>CYP2R1</it>. We also genotyped two common polymorphisms in <it>GC </it>gene (rs4588 and rs7041) by a PCR-restriction fragment length polymorphism (RFLP) method. We analyzed the association between these 4 polymorphisms and asthma susceptibility and asthma-related traits.</p> <p>Results</p> <p>Polymorphic markers in <it>VDR </it>and <it>CYP2R1 </it>were not associated with asthma in the Chinese Han cohort. Importantly, variants in <it>GC </it>gene, which give rise to the two most common electrophoretic isoforms of the vitamin D binding protein, were associated with asthma susceptibility. Compared with isoform Gc1, Gc2 was significantly associated with the risk of asthma (OR = 1.35, 95% CI = 1.01-1.78 p = 0.006).</p> <p>Conclusions</p> <p>The results provide supporting evidence for association between <it>GC </it>variants and asthma susceptibility in the Chinese Han population.</p

Membrane-encased polymer millirods for sustained release of 5-fluorouracil

Abstract: This article describes the design and development of a novel membrane-encased polymer millirod for the sustained release of an anticancer drug, 5-fluorouracil (5-FU). The millirod consists of two functional compartments: (1) an inner 5-FU-loaded monolithic millirod as the drug depot, and (2) an outer NaCl-impregnated polymer membrane to control the release rate of 5-FU. The inner millirod is fabricated by a compression-heat molding procedure to permit the entrapment of 5-FU particles in the poly(D,Llactide-co-glycolide) (PLGA) matrix. The drug loading density is controlled at 30 w/w% to achieve a burst release of 5-FU (&gt;90% of the drug are released within 48 h) from the monolithic millirod. The NaCl-impregnated PLGA membrane is generated by solvent casting and is then wrapped over the monolithic millirod to produce the membraneencased millirod. Scanning electron microscopy shows that dissolution of NaCl particles produces a semipermeable polymer membrane to provide a sustained release of 5-FU. The membrane thickness and the density of NaCl particles inside the membrane are useful parameters to control the release kinetics of 5-FU. Under the experimental conditions in this study, sustained release of 5-FU [rates between 0.1 and 0.4 mg/(day и cm of millirod)] is achieved for 2 to 5 weeks in phosphate-buffered saline (pH 7.4) at 37°C. Results from this study demonstrate that membrane-encased polymer millirods provide controllable sustained release kinetics for applications in intratumoral drug delivery