ILC2 influence the differentiation of alveolar type II epithelial cells in bronchopulmonary dysplasia mice.

Bronchopulmonary dysplasia, a common complication of premature infants, is mainly characterized by blocked alveolarization. Proverbially, the injury of alveolar type II epithelial cells is regarded as the pathologic basis of occurrence and development of bronchopulmonary dysplasia. In the case of alveolar epithelial damage, alveolar type II epithelial cells can also differentiate to alveolar type I epithelial cells as progenitor cells. During bronchopulmonary dysplasia, the differentiation of alveolar type II epithelial cells becomes abnormal. Group 2 innate lymphoid cells can produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Previous studies have shown that group 2 innate lymphoid cells can inhibit the alveolarization process of bronchopulmonary dysplasia by secreting IL-13. However, whether group 2 innate lymphoid cells can affect the differentiation of alveolar type II epithelial cells in the pathologic process of bronchopulmonary dysplasia remains unclear. In this study, we have shown that IL-13 secreted by group 2 innate lymphoid cells increased during bronchopulmonary dysplasia, which was related to the release of large amounts of IL-33 by impaired alveolar type II epithelial cells. This led to abnormal differentiation of alveolar type II epithelial cells, reduced differentiation to alveolar type I epithelial cells, and increased transdifferentiation to mesenchymal cells through the epithelial-mesenchymal transition. Taken together, our study provides a complementary understanding of the development of bronchopulmonary dysplasia and highlights a novel immune mechanism in the pathogenesis of bronchopulmonary dysplasia.

Type 2 innate lymphoid cell-derived amphiregulin regulates type II alveolar epithelial cell transdifferentiation in a mouse model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants characterized by alveolar growth arrest. Interleukin (IL)-33 and type 2 innate lymphoid cell (ILC2) affect type II alveolar epithelial cell (AECII) differentiation in BPD mice and may cause increased lung epithelial-mesenchymal transition (EMT). Amphiregulin (AREG) can be produced by ILC2 and is associated with tissue repair. However, the action mechanism of AREG produced by ILC2 to alveolar development in BPD is unclear. In this study, we aimed to demonstrate the role and mechanism of AREG in influencing AECII transdifferentiation in the lung tissue of BPD mice. The effects of ILC2-derived AREG on AECII transdifferentiation were verified in vivo and in vitro, and the role of IL-33 on ILC2-derived AREG in AECII transdifferentiation in BPD mice and a preliminary investigation of the role of AREG's receptor-epidermal growth factor receptor (EGFR) on AECII transdifferentiation. The results showed that neonatal mice developed severe lung injury after hyperoxia, and IL-33 induced AREG production via ILC2 affected normal AECII differentiation and promoted EMT. In addition, the blockade of EGFR was found to alleviate the impaired AECII differentiation under hyperoxia in an in vitro study. In summary, our study demonstrates that AREG secreted by ILC2 affects AECII transdifferentiation in BPD mice, which provides a new idea for the clinical treatment of BPD.

ILC2 regulates hyperoxia-induced lung injury via an enhanced Th17 cell response in the BPD mouse model.

BACKGROUD: Recent research has focused on the role of immune cells and immune responses in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact mechanisms have not yet been elucidated. Previously, the key roles of type 2 innate lymphoid cells (ILC2) in the lung immune network of BPD were explored. Here, we investigated the role Th17 cell response in hyperoxia-induced lung injury of BPD, as well as the relationship between ILC2 and Th17 cell response. METHODS: A hyperoxia-induced BPD mouse model was constructed and the pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining. Flow cytometry analysis was conducted to determine the levels of Th17 cell, ILC2 and IL-6+ILC2. The expression levels of IL-6, IL-17 A, IL-17 F, and IL-22 in the blood serum and lung tissues of BPD mice were measured by ELISA. To further confirm the relationship between ILC2 and Th17 cell differentiation, ILC2 depletion was performed in BPD mice. Furthermore, we used immunomagnetic beads to enrich ILC2 and then flow-sorted mouse lung CD45+Lin-CD90.2+Sca-1+ILC2. The sorted ILC2s were injected into BPD mice via tail vein. Following ILC2 adoptive transfusion, the changes of Th17 cell response and lung injury were detected in BPD mice. RESULTS: The expression levels of Th17 cells and Th17 cell-related cytokines, including IL-17 A, IL-17 F, and IL-22, were significantly increased in BPD mice. Concurrently, there was a significant increase in the amount of ILC2 and IL-6+ILC2 during hyperoxia-induced lung injury, which was consistent with the trend for Th17 cell response. Compared to the control BPD group, ILC2 depletion was found to partially abolish the Th17 cell response and had protective effects against lung injury after hyperoxia. Furthermore, the adoptive transfer of ILC2 enhanced the Th17 cell response and aggravated lung injury in BPD mice. CONCLUSIONS: This study found that ILC2 regulates hyperoxia-induced lung injury by targeting the Th17 cell response in BPD, which shows a novel strategy for BPD immunotherapy.

Clinical features and risk factors of lung cancer in elderly patients with dermatomyositis.

BACKGROUND: Although there are concerns about the association between dermatomyositis (DM) and malignancy, the clinical features in elderly DM patients with lung cancer are largely unknown. Here, we elucidated the clinical features and risk factors of lung cancer in elderly DM patients. METHODS: The data of elderly DM patients (≥65 years old) with or without lung cancer admitted to the Second Xiangya Hospital, Central South University from January 2016 to November 2022 were retrospectively analyzed. RESULTS: Male patients with elderly onset DM (EODM) symptoms were found to be prone to lung cancer (p < 0.001). Elderly DM patients with lung cancer had a higher ratio of a history of smoking and were more likely to present with heliotrope rash, V sign and dysphasia and elevated monocyte-to-lymphocyte ratio (MLR) and there was a higher ratio of anti-TIF1-γ-Ab-positive patients (all p < 0.05). Occurrence of interstitial lung disease (ILD), elevated aspartate aminotransferase (AST) and anti-aminoacyl-tRNA synthetase (anti-ARS)-antibody positive rates were less common in elderly DM patients with lung cancer than those without lung cancer (all p < 0.05). Multivariate logistic regression analysis showed smoking history (p = 0.011, OR = 4.532), elevated MLR (p = 0.018, OR = 1.159) and anti-TIF1-γ-Ab-positive status (p = 0.034, OR = 8.529) were independently associated with the presence of lung cancer, while ILD might be a protective factor (p = 0.024, OR = 0.179) for lung cancer in elderly patients with DM. CONCLUSIONS: Lung cancer is more common in male patients with EODM symptoms. Smoking, elevated MLR and being anti-TIF1-γ-Ab-positive were associated with higher frequencies of lung cancer in elderly DM patients. It is necessary to screen lung cancer in elderly DM patients with a history of smoking, elevated MLR or being anti-TIF1-γ-Ab-positive.

IL-33-ST2 pathway regulates AECII transdifferentiation by targeting alveolar macrophage in a bronchopulmonary dysplasia mouse model.

Evidence points to the indispensable function of alveolar macrophages (AMs) in normal lung development and tissue homeostasis. However, the importance of AMs in bronchopulmonary dysplasia (BPD) has not been elucidated. Here, we identified a significant role of abnormal AM proliferation and polarization in alveolar dysplasia during BPD, which is closely related to the activation of the IL-33-ST2 pathway. Compared with the control BPD group, AMs depletion partially abolished the epithelialmesenchymal transition process of AECII and alleviated pulmonary differentiation arrest. In addition, IL-33 or ST2 knockdown has protective effects against lung injury after hyperoxia, which is associated with reduced AM polarization and proliferation. The protective effect disappeared following reconstitution of AMs in injured IL-33 knockdown mice, and the differentiation of lung epithelium was blocked again. In conclusion, the IL-33-ST2 pathway regulates AECII transdifferentiation by targeting AMs proliferation and polarization in BPD, which shows a novel strategy for manipulating the IL-33-ST2-AMs axis for the diagnosis and intervention of BPD.

Role of air pollution in systemic lupus erythematosus. / 空气污染在系统性红斑狼疮发生发展中的作用.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can affect almost every organ in the human body. The etiology and pathogenesis are unclear. Recent studies have shown that pathogenesis and development of SLE result from the interaction between various internal and external factors. Current studies suggest that air pollution may increase the risk of SLE through multiple mechanisms such as inducing immune disorders, causing epigenetic changes, and inducing oxidative stress. Air pollution has a certain relationship with pulmonary interstitial lesions, lupus nephritis, decreased reproductive function and other system damages in SLE patients, and it is related to the occurrence and clinical outcomes of SLE. Air pollution has a potential role in the occurrence and development of SLE, providing a brand-new view on the early prevention and control of SLE.

Effect of miR-124a on collagen-induced arthritis in mice and the underlying mechanisms. / MiR-124aå¯¹èƒ¶åŽŸè¯±å¯¼æ€§å ³èŠ‚ç‚Žå°é¼ çš„å½±å“åŠå ¶æœºåˆ¶.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease. MicroRNA has been shown to play an important role in RA. MicroRNA-124a (miR-124a) has anti-proliferative and anti-inflammatory effects in RA fibroblast synovial cells. This study aims to explore the effects of miR-124a overexpression on arthritis in collagen-induced arthritis (CIA) mice and the underlying mechanisms. METHODS: Bovine type II collagen and complete Ferris adjuvant were used to induce CIA model from DBA/1 mice. Twenty-eight days after initial immunization (D28), CIA mice were randomly divided into a model group, a miR-124a treatment group, and a negative control (NC) group. Physiological saline, miR-124a agomir, and miR-124a agomir NC were injected into the skin at the tail root of mice every 3 days for 4 times, respectively. The degree of joint swelling and arthritis index of mice were recorded accordingly. Sixty-three days after initial immunization (D63), the mice were sacrificed to obtain the synovial tissue of ankle joint. HE staining was used to observe the proliferation of synovial cell, infiltration of inflammatory cell, pannus, and bone erosion of synovial tissues; TUNEL staining was used to detect cell apoptosis; qRT-PCR was used to detect the mRNA expression of miR-124a, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) and its downstream genes Bcl-2 and Bax. Immunohistochemistry was used to detect the protein expression of PIK3CA, Bcl-2, and Bax protein in synovial tissues of each group. RESULTS: Different degrees of swelling presented in the paws of DBA/1 mice at D28, which indicated the CIA model was constructed successfully. Forty-eight days after initial immunization (D48), the paws of mice in the miR-124a treatment group were only slightly red and swollen, while the paws of mice in the model group and the NC group were obviously red and swollen. The arthritis index of mice in the miR-124a treatment group were decreased significantly compared to the NC group at D51, D53, D59, and D62 (51, 53, 59, 62 days after initial immunization) (all P<0.05). Sixty-three days after initial immunization (D63), HE staining indicated that the scores of synovial cell proliferation, inflammatory cell infiltration, synovial pannus, and bone erosion were significantly reduced in the miR-124a treatment group (P<0.05 or P<0.01), while cell apoptosis was increased in the miR-124a treatment group compared with the model group and NC group (P<0.01 or P<0.001). Besides, the expression of miR-124a and Bax in the synovial tissue in miR-124a treatment group was significantly higher than those in the model group and NC group (P<0.01 or P<0.001), while the expressions of PIK3CA and Bcl-2 were decreased (P<0.05 or P<0.01 or P<0.001), and the ratio of Bcl-2 to Bax was significantly decreased (P<0.01 or P<0.001). CONCLUSIONS: Overexpression of miR-124a can reduce arthritis in CIA mice bacause it could promote synovial cell apoptosis and inhibit synovial cell proliferation via targeting PIK3CA and regulating its downstream pathways.

Dynamic Changes of NCR- Type 3 Innate Lymphoid Cells and Their Role in Mice with Bronchopulmonary Dysplasia.

Inflammation is one of the important pathogenesis of bronchopulmonary dysplasia (BPD). Type 3 innate lymphoid cells (ILC3) play a role in a variety of inflammatory lung diseases. In this study, we established the BPD model by injecting lipopolysaccharide into the amniotic cavity of pregnant mice. Here, we investigated the dynamic changes of ILC3 and NKP46- ILC3 population in lung tissues of mice from BPD and the control groups. Results showed that the proportion of ILC3 and NKP46-ILC3 in the BPD group was higher than those of the control group. In addition, the cytokines interleukin-17 (IL-17) and interleukin-22 (IL-22) secreted by ILC3 in this model had also changed that their expression was significantly increased compared with that of the control group. Flow cytometry demonstrated that ILC3 were a rapid source of IL-17. In the anti-CD90 knockdown experiment, we confirmed the alleviation of BPD inflammation in the absence of ILC3. In addition, we injected mice with anti-IL-17 neutralizing antibody, and the results showed that IL-17 could aggravate BPD inflammation. Taken together, ILC3 may play a pro-inflammatory role in BPD by secreting IL-17.

Dry-deposition of inorganic and organic nitrogen aerosols in Xiamen Bay: Fluxes, sources, and biogeochemical significance.

Increased dry deposition of nitrogen aerosols (aerosol-N) as a result of anthropogenic emissions has caused large negative impacts on marine ecosystems. We monitored the number concentrations and sizes of inorganic nitrogen aerosols (aerosol-IN: NH4+ and NO3-) and organic nitrogen aerosols (aerosol-ON: methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, and triethylamine) by single-particle aerosol mass spectrometry (SPAMS) during the warm season (WS) and cold season (CS) of 2013 and 2015 in Xiamen Bay. The mean hourly number concentration of aerosol-IN (874/h) overwhelmed that of aerosol-ON (103/h), accounting for 83.9 ± 16.1% of aerosol-N. More than 90% of aerosol-N was concentrated in the condensation mode (0.1-0.5 µm) and droplet mode (0.5-2.0 µm). Aerosol-IN was the main contributor (80.1-94.2%) to aerosol-N deposition. New production potentially supported by the ocean's external nitrogen supply provided aerosol-N input of 11.51-11.96 g C m-2 yr-1, which contributed 17.5-18.2% of total new production in the southern East China Sea. Four potential sources of aerosol-N were identified based on the results of positive matrix factorization analysis, including secondary formation (F1), biogenic source (F2), sea spray, soil dust, biomass burning (F3), and anthropogenic sources (F4). Aerosol-N concentrations in Xiamen Bay were mainly affected by the ocean air masses during the WS and inland air masses during the CS. The percentages of aerosol-N at each backward trajectory cluster showed that the inland air masses brought more aerosol-IN emitted from biomass burning, soil dust, and secondary formation sources, whereas the ocean air masses brought more aerosol-ON emitted from a marine biogenic source into Xiamen Bay. This study provides an example of determining the number concentrations and sizes of IN and ON in aerosols by SPAMS, and helps us further understand the dry deposition and sources of IN and ON in aerosols in Xiamen Bay.

Non-ignorable contribution of anthropogenic source to aerosols in Arctic Ocean.

Arctic Ocean (AO) atmospheric aerosols, which are a factor influencing regional and global climate, have been greatly influenced by an increase in anthropogenic sources. To identify the impact of anthropogenic sources on regional aerosols in the AO and middle and low latitudes (MLO), a single-particle aerosol mass spectrometer was used to count and size aerosols with diameters less than 2.5 µm (PM2.5) and determine their chemical composition. The mean hourly count of PM2.5 aerosols was 1639/h in the AO, which was 57.1% lower than that in the MLO. Na_MSA, sulfate, and Na_rich were three major components, which accounted for 74.3% of PM2.5 aerosols in the AO. The size distribution of PM2.5 aerosols was unimodal, peaking between 0.42 µm and 1.64 µm. A source apportionment method for single aerosol particles in the Arctic was established using positive matrix factorization (PMF) combined with backward air mass trajectory and principal component analysis (PCA). Three potential sources of aerosols were identified: marine sources; anthropogenic sources; and secondary formation. The largest contribution to aerosols in the AO was from marine sources, accounting for 50.6%. This source was 20.4% higher in the AO than that in the MLO. Secondary formation contributed 19.8% and 36.5% to aerosols in the AO and MLO, respectively. However, the contribution of anthropogenic sources to aerosols was 29.6% in the AO, and this was 3.7% lower than that in the MLO. Our study provides a useful method for identifying sources of aerosols in the Arctic, and the results showed that although marine sources were the largest contributors to aerosols in the AO, the contribution of anthropogenic sources could not be ignored.

Tissue-Resident Type 2 Innate Lymphoid Cells Arrest Alveolarization in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a severe complication of the respiratory system associated with preterm birth. Type 2 innate lymphoid cells (ILC2s) play a major role in tissue homeostasis, inflammation, and wound healing. However, the role in BPD remains unclear. The present study showed that ILC2s, interleukin-4 (IL-4), IL-13, and anti-inflammatory (M2) macrophages increased significantly in BPD mice as compared to the control mice. Administration with recombinant mouse IL-33 amplified the above phenomena and aggravated the alveolar structural disorder and functional injury in mice subjected to BPD, and the opposite was true with anti-ST2 antibody. In addition, the depletion of ILC2s in BPD mice with anti-CD90.2 antibody substantially abolished the destructive effect on BPD. In the treatment of BPD with dexamethasone, the number of ILC2s and M2 macrophages and levels of IL-4 and IL-13 decreased with remission as compared to the control group. This study identified a major destructive role of the ILC2s in BPD that could be attenuated as a therapeutic strategy.

[The number of ILC3 and their related cytokines IL-17 and IL-22 increase in lungs of mice with bronchopulmonary dysplasia].

Objective To investigate dynamic changes of type 3 innate lymphoid cells (ILC3) in lungs of mice with bronchopulmonary dysplasia (BPD). Methods Forty newborn C57BL/6 mice were randomized into air group and the hyperoxia group, 20 mice in each group. C57BL/6 newborn mice were delivered by caesarean section on the 19th day of pregnancy and exposed to 850 mL/L O2 for replication of the BPD model. Five mice in each group were sacrificed 1 day, 3, 7, 14 days after they were born for procurement of fresh lung tissues. HE staining was used to observe the pathological changes of lung tissues. ELISA was used to detect the protein content of downstream cytokines interleukin-17 (IL-17), IL-22 and granulocyte-macrophage colony stimulating factor (GM-CSF) in lung homogenate. Flow cytometry was used for measuring the proportion of ILC3 in lymphocytes as well as the proportions of IL-17+ ILC3 and IL-22+ ILC3 in the lung. Results The proportion of ILC3 in lung tissues reached the peak on the 7th day after birth. In contrast with the air group, the proportion of ILC3 in the hyperoxia group was significantly elevated at the same time points. The protein content of IL-17 and IL-22 in the hyperoxia group went up significantly in comparison with those in the air group at the same time points, while the GM-CSF content in the hyperoxia group showed no significant changes. The proportions of IL-17+ILC3 and IL-22+ILC3 in the hyperoxia group significantly increased as compared with those in the air group at the same time points. Conclusion The secretion of IL-17 and IL-22 derived from ILC3 is associated with BPD.

Effect of sea ice retreat on marine aerosol emissions in the Southern Ocean, Antarctica.

Sea ice retreat in the polar region is expected to increase the emissions of sea salt aerosols and biogenic gases, which may significantly impact the climate by increasing cloud condensation nuclei (CCN) population and changing solar radiation. In this study, aerosol compositions were measured at high-time-resolution (1 h) with an in-situ gas and aerosol composition monitoring system in polynya regions of the Southern Ocean (SO) to access the effects of sea ice concentrations on the sea salt aerosol (SSA) and secondary biogenic aerosol (SBA) in the SO. SSA emissions increased by more than 30% as sea ice concentration decreased from 85% to 29%. However, SSA emissions did not increase monotonically as the sea ice concentration decreased. The highest SSA concentration occurred in drifting sea ice region. Sea ice melting increased SBA concentrations by enhancing the air-sea exchanges of SBA precursor gases and the release of algae from sea ice. Positive correlations between SSA and wind speed were present in different sea ice regions, while SBA didn't reveal an obvious correlation with wind speed in the SO. The impact of wind speed on the SSA emissions were very different, Higher slope value of 41.83 and 35.81 were present in the DSI and SIF region, while the value was only about 16.74 in the SIC region. The results extended the knowledge of the effect of future sea ice retreat on marine aerosol emissions and potential climate changes in the polar region.

Significant Underestimation of Gaseous Methanesulfonic Acid (MSA) over Southern Ocean.

Methanesulfonic acid (MSA), derived from the oxidation of dimethylsulfide (DMS), has a significant impact on biogenic sulfur cycle and climate. Gaseous MSA (MSAg) has been often ignored in previous studies due to its quick conversion to particulate MSA (MSAp) and low concentrations. MSAg, MSAp, and nss-SO42- were observed simultaneously for the first time with high-time-resolution (1 h) in the Southern Ocean (SO). The mean MSAg level reached up to 3.3 ± 1.6 pptv, ranging from ∼24.5 pptv in the SO, contributing to 31% ± 3% to the total MSA (MSAT). A reduction of the MSA to nss-SO42- ratios by about 30% was obtained when MSAg was not accounted for in the calculation, indicating that MSAg was very important in the assessment of the biogenic sulfur contributions in the atmosphere. Mass ratios of MSA to nss-SO42- increased first and then decreased with the temperature from -10 to 5 °C, with a maximum value at the temperature of -3 °C. Positive correlations between MSAg to MSAT ratios and temperature were presented, when the temperature was higher than 5 °C. This study highlights the importance of MSAg for understanding the atmospheric DMS oxidation mechanism and extends the knowledge of MSA formation in the marine atmosphere.

[Structural features of intestinal flora in preterm rats with cognitive impairment: an analysis based on high-thorough sequencing].

OBJECTIVE: To study the structural features of intestinal flora in preterm rats with cognitive impairment and the association of the change in intestinal flora with cognitive impairment in preterm rats. METHODS: Sprague-Dawley rats at 16-17 days of gestation were intraperitoneally injected with lipopolysaccharide for two consecutive days to establish a model of cognitive impairment, and the rats treated with intraperitoneally injected phosphate-buffered saline were established as the control group. Cesarean section was performed on day 21 of gestation, and preterm rats were randomly assigned to healthy maternal rats for feeding. The place navigation test in the Morris water maze was used to evaluate cognition on day 30 after birth. According to the result, the preterm rats were divided into cognitive impairment group with 21 rats and normal control group with 10 rats. Hematoxylin and eosin staining was used to observe pathological changes of the hippocampus, and fecal samples were collected for 16S rRNA sequencing and analysis. A principal component analysis (PCA) was performed for intestinal flora. RESULTS: Compared with the normal control group, the cognitive impairment group showed degeneration and necrosis of a large number of neurons in the hippocampus. Compared with the normal control group, the cognitive impairment group had significant reductions in the abundance and diversity of intestinal flora (P<0.05), with a significant increase in the abundance of Proteobacteria at the phylum level (P<0.05), as well as significant reductions in the abundance of Prevotella and Lactobacillus and significant increases in the abundance of Staphylococcaceae and Oligella at the order, family, and genus levels (P<0.05). PCA showed a significant difference in the composition of intestinal flora between the two groups. CONCLUSIONS: There is a significant change in the structure of intestinal flora in preterm rats with cognitive impairment, which provides a basis for the treatment and intervention of microecological changes due to cognitive impairment after preterm birth.

[Association of short-term efficacy for infliximab in rheumatoid arthritis with plasma concentration and anti-drug antibody].

OBJECTIVE: To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.

[Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis].

OBJECTIVE: To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).
 Methods: Twelve patients with severe refractory RA were treated with tocilizumab. The clinical and laboratory indices and the side effects were recorded after treatment.
 Results: The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients, which were significantly improved after TCZ therapy (P<0.05), and no obvious adverse reactions were found.
 Conclusion: Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Decrease in the CO2 uptake capacity in an ice-free Arctic Ocean basin.

It has been predicted that the Arctic Ocean will sequester much greater amounts of carbon dioxide (CO2) from the atmosphere as a result of sea ice melt and increasing primary productivity. However, this prediction was made on the basis of observations from either highly productive ocean margins or ice-covered basins before the recent major ice retreat. We report here a high-resolution survey of sea-surface CO2 concentration across the Canada Basin, showing a great increase relative to earlier observations. Rapid CO2 invasion from the atmosphere and low biological CO2 drawdown are the main causes for the higher CO2, which also acts as a barrier to further CO2 invasion. Contrary to the current view, we predict that the Arctic Ocean basin will not become a large atmospheric CO2 sink under ice-free conditions.