LncRNA HOTTIP regulates TLR4 promoter methylation by recruiting H3K4 methyltransferase MLL1 to affect apoptosis and inflammatory response of fibroblast-like synoviocyte in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the role of HOXA transcript at the distal tip (HOTTIP) in its pathogenesis remains underexplored. This study investigates the mechanism by which HOTTIP influences apoptosis and the inflammatory response of fibroblast-like synoviocytes (FLS). An RA mouse model was established, and clinical scores were analyzed. Pathological changes in synovial tissues, bone mineral density (BMD) of the paws, serum tartrate-resistant acid phosphatase (TRAP) activity, and TNF-α and IL-1ß levels were assessed. FLS were transfected, and cell proliferation and apoptosis were examined. The RNA-pull-down assay determined HOTTIP's interaction with mixed-lineage leukemia 1 (MLL1), while RNA immunoprecipitation assay measured HOTTIP expression pulled down by MLL1. The levels of MLL1 and toll-like receptor 4 (TLR4) after MLL1 overexpression based on HOTTIP silencing were determined. Chromatin immunoprecipitation (ChIP) was performed with H3K4me3 as an antibody, followed by the evaluation of TLR4 expression. HOTTIP expression was elevated in RA mouse synovial tissues. Inhibition of HOTTIP led to reduced clinical scores, inflammatory infiltration, synovial hyperplasia, TRAP activity, and TNF-α and IL-1ß levels, along with increased BMD. In vitro Interference with HOTTIP suppressed RA-FLS apoptosis and inflammation. HOTTIP upregulated TLR4 expression by recruiting MLL1 to facilitate TLR4 promoter methylation. MLL1 overexpression reversed HOTTIP silencing-mediated repression of RA-FLS apoptosis. Activation of H3K4 methylation counteracted HOTTIP knockout, ameliorating the inflammatory response. HOTTIP regulates TLR4 expression by recruiting MLL1, leading to TLR4 promoter methylation, thereby suppressing RA-FLS proliferation and inducing cell apoptosis and inflammatory response in RA.

The mediating effects of adversity quotient and self-efficacy on ICU nurses' organizational climate and work engagement.

AIM: This study aimed to explore the mediating effects of adversity quotient and the moderating effect of self-efficacy on the relationship between the organizational climate and the work engagement of intensive care unit nurses. BACKGROUND: A good organizational climate can contribute to a high level of work engagement. Adversity quotient and self-efficacy are the key factors affecting nurses' work engagement, while the mechanism of these factors in the organizational climate and work engagement remains unclear. This study was conducted to contribute to the relevant field research. METHODS: The study used a cross-sectional research design and surveyed 323 intensive care unit nurses working in a public hospital in China. The data were analysed using descriptive statistical methods: Pearson correlation analysis and PROCESS macro Model 7 in the regression analysis. RESULTS: Organizational climate was positively correlated with work engagement and adversity quotient. The indirect effect of organizational climate on work engagement through adversity quotient was positive. Furthermore, self-efficacy moderated the relationship between the two factors. CONCLUSION: Cultivating organizational climate and adversity quotients is an important strategy to improve the work engagement of intensive care unit nurses, particularly for nurses with high self-efficacy. IMPLICATIONS FOR NURSING MANAGEMENT: Administrators should make efforts to create a good organizational climate and cultivate nurses' adversity quotients and self-efficacy to decrease their intent to leave.

Reversal of hepatorenal syndrome and kidney recovery: When renal has more to offer.

Hepatorenal syndrome (HRS) is one of the most severe complications in advanced cirrhosis. Type-1 HRS is relatively uncommon, yet carries considerably higher mortality rate. Effective treatment for HRS, especially therapy towards survival benefits, is still limited. However, the role for dialysis in HRS has been questioned over the years. The initiation of dialysis remains controversial for those who aren't transplant candidates. Meanwhile, there's a growing attention towards the successful use of peritoneal dialysis (PD) in cirrhotic patients. Herein, we report a case of HRS-1 in a 76-year-old male patient with decompensated cirrhosis. Through a series of adjustments of hemodialysis regimens and pharmacological prescriptions, patient stabilized and the opportunity for transjugular intrahepatic portosystemic shunt (TIPS) insertion was gained. PD was initiated after TIPS placement. With a gradual decrease of dialysis dose, patient successfully weaned off PD and achieved both reversal of HRS and kidney recovery. Markedly improved nutritional status and quality of life were reported. The potential role of dialysis and TIPS in HRS may be worth revisiting. Further studies regarding the optimal timing of dialysis initiation, choices of dialysis modality, and efficacy of dialysis therapy in combination with TIPS in HRS patients are warranted.

[Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3+ CD4+ and CD3+ CD8+ lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant. CONCLUSION: The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

Plasma chemokine CXC motif-ligand 16 as a predictor of renal prognosis in immunoglobulin A nephropathy.

BACKGROUND: There are few non-invasive biomarkers that have been identified to improve the risk stratification of patients with IgA nephropathy (IgAN). CXCL16 has been shown to play a key role as a chemoattractant, adhesion, and fibrosis factor in inflammatory disease. This study evaluated the potential for CXCL16 plasma as a potential biomarker in patients with IgAN. METHODS: Plasma CXCL16 was measured in 230 patients with renal biopsied IgAN enrolled from 2012 to 2014. The patients were followed for 41.3 months, with a 50% reduction in estimated glomerular filtration rate or end-stage renal disease as endpoints. RESULTS: The plasma CXCL16 levels in IgAN patients were strongly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. Furthermore, counts of CD4+ T cells, CD8+ T cells, and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Lastly, we concluded that patients with higher levels of plasma CXCL16 had an increased risk of poor renal outcome compared to those with lower levels. There was no association between the polymorphisms and clinical parameters of CXCL16, including the levels and prognosis of plasma CXCL16. CONCLUSIONS: Plasma CXCL16 levels were associated with clinical parameters; pathological damage; CD4+ T cell, CD8+ T cell, and CD20+ B cell infiltration in renal tissue; and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.

A porcine alveolar macrophage cell line stably expressing CD163 demonstrates virus replication and cytokine secretion characteristics similar to primary alveolar macrophages following PRRSV infection.

The in vitro investigation of cytokine secretion induced by porcine reproductive and respiratory syndrome virus (PRRSV) requires porcine alveolar macrophages (PAMs) and their interaction with immunocytes. However, immortalized monoclonal PAMs (mPAMs) are non-permissive for PRRSV infection. The porcine CD163 receptor isolated from primary PAMs (pPAMs) confers susceptibility to PRRSV infection; thus, this approach could be used to establish a novel cell line to facilitate the exploration of PRRSV infection kinetics. Here, we amplified the coding region of the CD163 gene from pPAMs and integrated it into an mPAM line using a lentivirus expression system. After verification, the monoclonal PAM cell line stably expressing CD163 (mPAM-CD163-GFP) was infected with either the highly pathogenic PRRSV strain JXA1 or the classical PRRSV strain SD1, which produced high infectious titers of progeny virus reaching > 109 copies/mL or a 50 % tissue culture infective dose of 105.5 over at least 100 cell generations. We also investigated cytokine and Toll-like receptor expression in infected mPAM-CD163-GFP cells and pPAMs. The mPAM-CD163-GFP cell line showed similar patterns of viral replication and cytokine secretion compared with pPAMs, so it may be extremely useful for replacing primary cells for in vitro investigations of the mechanisms of cytokine secretion and interactions between PRRSV-infected PAMs and immunocytes.

Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice.

Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Although some studies reported the roles of Retinoid acid induced 16 (RAI16) in the tumorigenesis of hepatocellular carcinoma and PKA signaling, the roles of RAI16 in IBD and CRC are undressed. RAI16-/- mice were generated and the roles of RAI16 were addressed in dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS induced IBD or CAC mouse models, respectively. At first, RAI16-/- mice were viable, fertile with no apparent defects. Then, it was found that RAI16-/- mice were more susceptibility to colitis induced by DSS than wild type (WT) littermates, which was evaluated by disease activity index and histological score. Furthermore, the expressions of tissues repair associated molecules Cox2, Ereg and MMP-10 were significantly decreased in RAI16-/- colon under DSS treatment. Gut barrier related genes including antimicrobial peptides Reg3b and Reg3g and intestinal mucus genes Muc4, Muc6 and Muc20 were reduced in RAI16-/- colon. These findings indicated that RAI16 may function to affect genes involved in intestinal barrier function and immunoprotective inflammation. Accordingly, RAI16-/- mice displayed significantly increased tumor burden compared with WT mice assessed in CAC model induced by AOM/DSS. Much more Ki67 + nuclei were observed in RAI16-/- tumors suggesting RAI16 to be critical in colonic cell proliferation during tumorigenesis. Conclusively, we demonstrate the roles of RAI16 in colonic inflammation and inflammation-associated tumorigenesis by using a novel RAI16-/- mouse model for the first time.

How to design more efficient hole-transporting materials for perovskite solar cells? Rational tailoring of the triphenylamine-based electron donor.

Designed with a symmetrical naphthatetrathiophene (NTT) core and triphenylamine (TPA)-based side arms, a series of novel organic small molecule hole-transporting materials are simulated for perovskite solar cells (PSCs) using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. As a fundamental understanding, the energy level alignments and the charge transport behavior are explored for their potential applications. Our results show that, adding an oxygen-bridge between the neighboring phenyl groups of TPA side arms makes the highest occupied molecular orbital (HOMO) levels up-shift, whereas the carbon-carbon single bond stabilizes the HOMOs by about 0.3-0.4 eV. By structural tailoring of the TPA side arms, the HOMO levels of newly designed molecules range from -5.08 eV to -5.61 eV, which provides more possibilities for the interfacial energy regulation. Meanwhile, our results also indicate that the quasi-planar molecular architecture and the delocalized frontier molecular orbitals can effectively enhance the electronic coupling between adjacent molecules. In addition, the reorganization energies are distinctly lowered in the cases of the mixed carbon-carbon bond and oxygen-bridge, and the double oxygen-bridge models. As a result, these molecules with the additional carbon-carbon bond and oxygen-bridge exhibit high hole mobilities. Several promising candidates are proposed toward more efficient PSCs, and more importantly, this work offers some new insights for the design of organic small molecule materials.

TRIM65 is a potential oncogenic protein via ERK1/2 on Jurkat and Raji cells: A therapeutic target in human lymphoma malignancies.

In human lung cancer, Tripartite motif 65 (TRIM65) is documented as an important regulator in carcinogenesis. Knockdown of TRIM65 prevents the tumorigenesis of lung cancer cells, while TRIM65 overexpression presents the opposite effect. However, the roles of TRIM65 in human lymphocyte malignancies have reported little. Herein, we found that Jurkat (T-lymphocyte) and Raji (B-lymphocyte) expressed TRIM65. We aimed to investigate whether TRIM65 was a potential oncogenic protein that regulated the tumorigenesis of Jurkat and Raji cells. In our present study, cells were transfected with siRNA-TRIM65 or TRIM65 overexpression vector, Cell counting kit-8 (CCK-8), Flow cytometry and Annexin V-FITC/propidium iodide (PI) staining was carried out to detect cell viability, cell cycle profile and cell apoptosis, respectively. Extracellular signal-regulated kinases 1/2 (ERK1/2) pathway-associated proteins, such as Bcl2, cleaved-caspase 3, vascular endothelial growth factor (VEGF), and phosphorylated ERK1/2 (p-ERK1/2) were assessed. Our data indicated that knockdown of TRIM65 prevented the tumorigenesis of Jurkat and Raji cells. TRIM65 silencing inhibited cell proliferation, promoted cell apoptosis and arrested cell cycle, highly like through blocking ERK1/2 pathway. However, TRIM65 overexpression enhanced cell viability, increased the protein levels of Bcl2, VEGF, p-ERK1/2 while decreased cleaved-caspase 3 expression, suggesting the promoted effect of TRIM65 overexpression in the tumorigenesis of those two lymphoma cells. To validate the involvement of ERK1/2 pathway, ERK1/2 inhibitor AZD8330 (1 µmol/L) was introduced. We found that AZD8330 significantly prevented TRIM65 overexpression-induced tumorigenesis. We concluded that TRIM65 served as a potential oncogenic protein on Jurkat and Raji cells, and ERK1/2 pathway was the underlying mechanism. Approaches targeting TRIM65 provided a novel strategy for the treatment of lymphoma.

Screening host proteins required for bacterial adherence after H9N2 virus infection.

H9N2 subtype low pathogenic avian influenza virus (LPAIV) is distributed worldwide and causes great economic losses in the poultry industry, especially when complicated with other bacterial infections. Tissue damages caused by virus infection provide an opportunity for bacteria invasion, but this mechanism is not sufficient for low pathogenic strains. Moreover, although H9N2 virus infection was demonstrated to promote bacterial infection in several studies, its mechanism remained unclear. In this study, infection experiments in vivo and in vitro demonstrated that the adhesion of Escherichia coli (E. coli) to host cells significantly increased after H9N2 virus infection, and this increase was not caused by pathological damages. Subsequently, we constructed a late chicken embryo infection model and used proteomics techniques to analyze the expression of proteins associated with bacterial adhesion after H9N2 virus infection. A total of 279 significantly differential expressed proteins were detected through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis. The results of Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that differentially expressed proteins were enriched in host innate immunity; cell proliferation, differentiation, and apoptosis; and pathogenicity-related signaling pathways. Finally, we screened out several proteins, such as TGF-ß1, integrins, cortactin, E-cadherin, vinculin, and fibromodulin, which were probably associated with bacterial adhesion. The study analyzed the mechanism of secondary bacterial infection induced by H9N2 virus infection from a novel perspective, which provided theoretical and data support for investigating the synergistic infection mechanism between the H9N2 virus and bacteria.

RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection.

Influenza H7N9 virus infection causes an acute, highly contagious respiratory illness that triggers cell death of infected cells and airway epithelial destruction. RIP3 is a key regulator of cell death responses to a growing number of viral and microbial agents. This study aimed to investigate the role of RIP3 in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-) mice and littermate wild type mice were infected intranasally with influenza H7N9 virus (A/Fujian/S03/2015) to determine the contribution of RIP3 to the inflammatory response of influenza H7N9 virus infection. It was found that RIP3-/- mice infected with H7N9 virus showed higher survival and less weight loss, compared with wild type littermate mice. In addition, RIP3-/- mice had fewer regions of edema, infiltration with inflammatory cells, and alvelolar collapses, and the secretions of IL-1ß, IL-6, RANTES and MIP-1 in BALF were significantly decreased on days 3 and 7 p.i. when compared with WT mice. Moreover, caspase 1/IL1ß signaling was found to be invovled in RIP3 associated imflammation of influenza H7N9 virus, but not RIP3/MLKL dependent necrosis. In the conclusion, our results indicated that RIP3 deficiency can protect mice from the infection of influenza H7N9 virus by downregulating caspase 1/IL1ß signaling, which provided edivence of the RIP3 invovled necroptosis independent manner.

RIP3 deficiency exacerbates inflammation in dextran sodium sulfate-induced ulcerative colitis mice model.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease. The receptor-interacting protein kinase 3 (RIP3) was reported to be involved in many inflammatory disease. However, the mechanism of RIP3 in the pathogenesis of UC is still unclear. To investigate the effects and possible mechanism of RIP3 in UC pathogenesis, RIP3-/- mice was used in dextran sulfate sodium (DSS)-induced colitis model. It was found that by DSS-induced colitis, RIP3-/- mice showed significantly enhanced colitis symptoms, including increased weight loss, colon shortening, and colonic mucosa damage and severity, but decreased production of interleukin 6 and interleukin 1ß. The results showed that RIP3 deficiency could not ameliorate but exacerbate the severity of colitis. On the mechanism, it was found that messenger RNA expressions of several repair-associated cytokines including interleukin 6, interleukin 22, cyclooxygenase 2, epithelial growth factor receptor ligand Epiregulin and matrix metalloproteinase 10 were siginificant decreased in RIP3-/- mice. Thus, RIP3-/- mice exhibited an impaired tissue repair in response to DSS. In a conclusion, RIP3 deficiency exerted detrimental effects in DSS induced colitis partially because of the impaired repair-associated cytokines expression.

Fraunhofer diffraction of electromagnetic radiation by finite periodic structures with regular or irregular overall shapes.

Based on an essentially different theoretical foundation than common classical diffraction theories that remain in extensive use, this paper discusses from a fresh perspective the theoretical interpretation and prediction of the far-field diffraction of a plane monochromatic wave by a finite periodic array (PA) of identical obstacles. The theoretical treatment rests on the PA extension of the rigorous generalized multiparticle Mie solution (GMM). The truncated periodic structures may have an irregular overall shape with an arbitrary spatial orientation with respect to the incident beam. It is shown that the overall shape and intrinsic geometrical structure of a finite PA play a decisive role in giving rise to an associated far-field diffraction pattern. It is also shown that, when the physical dimensions of individual component units are much smaller than the incident wavelength, the extracted diffraction pattern of a densely packed PA of such small volumes in forward directions exhibits the distinct features predicted from classical diffraction theories for an aperture with the same shape as the overall finite PA. Several typical examples are presented, including two complementary arrays used in the specific discussion concerning Babinet's principle. There are brief preliminary discussions on some fundamental concepts in connection with the involved theoretical basis and on potential further development and application of the present GMM-PA approach.

Scattering of electromagnetic radiation by three-dimensional periodic arrays of identical particles.

The generalized multiparticle Mie-solution (GMM), a Lorenz-Mie-type rigorous theory for the scattering of a monochromatic plane wave by an arbitrary configuration of nonintersecting scattering bodies, has lately been revisited and further developed. A recent progress is the initiation of a special version applied to one- and two-dimensional (1D and 2D) periodic arrays (PAs) of identical particles [J. Opt. Soc. Am. A30, 1053 (2013)]. As a continuous advance, the present work extends the initiative PA-type solution from 1D and 2D to the more involved three-dimensional (3D) regular arrays. Analytical formulations applicable to the 3D PAs are derived, including the special PA-type explicit expressions for cross sections of extinction, scattering, backscattering, and radiation pressure. The specific PA-version is a complement to the general formulation and solution process of the standard GMM. In either 1D and 2D or 3D cases, the newly devised PA-approach is capable of providing expeditiously theoretical predictions of radiative scattering characteristics for periodic structures consisting of a huge number of identical unit cells, which the general approach of the GMM is unable to handle in practical calculations, owing to excessive computing time and/or computer memory requirements. To illustrate practical applications, sample numerical solutions obtained via the PA-approach are shown for 3D PAs of finite lengths that have ∼5×10(7) component particles, including structures having a rectangular opening. Also discussed is potential future work on the theory and its tests.

Scattering of electromagnetic waves by periodic particle arrays.

The generalized multiparticle Mie-solution (GMM) is an extension of the well-known Mie-theory for single homogeneous spheres to the general case of an arbitrary ensemble of variously sized and shaped particles. The present work explores its specific application to periodic structures, starting from one- and two-dimensional regular arrays of identical particles. Emphasis is placed on particle arrays with a truncated periodic structure, i.e., periodic arrays (PAs) with finite overall dimensions. To predict radiative scattering characteristics of a PA with a large number of identical particles within the framework of the GMM, it is sufficient to solve interactive scattering for only one single component particle, unlike the general case where partial scattered fields must be solved for every individual constituent. The total scattering from an array as a whole is simply the convolution of the scattering from a single representative scattering center with the periodic spatial distribution of all replica constituent units, in the terminology of Fourier analysis. Implemented in practical calculations, both computing time and computer memory required by the special version of GMM formulation applicable to PAs are trivial for ordinary desktops and laptops. For illustration, the radiative scattering properties of several regular arrays of identical particles at a fixed spatial orientation are computed and analyzed. Numerical results obtained from the newly developed approach for PAs are compared with those calculated from the general GMM computer codes (that have been available online for about a decade). The two sets of numerical outputs show no significant relative deviations. However, the CPU time required by the specific approach for PAs could drop more than 10,000 times, in comparison with the general approach. In addition, an example PA is also presented, which consists of as large as 10(8) particles and the general solution process is unable to handle.

Effect of partial liquid ventilation on lung function in oleic acid-induced lung injury model of piglets.

BACKGROUND: Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Partial liquid ventilation (PLV) has been developed as an alternative ventilatory strategy for treating severe lung injury. The aim of this study is to investigate the effect of PLV on lung function in immature piglets. METHODS: Acute lung injury was induced in 12 Chinese immature piglets by oleic acid (OA). The animals were randomly assigned to two groups (n = 6 each group): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. Mean arterial blood pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), left atrial pressure (LAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), cardiac output (CO), mean pressure of airway (Paw), dynamic lung compliance (Cydn), and arterial blood gases were measured during the observation period. RESULTS: No piglet died in either group with severe lung injury. After four hours of ventilation, pH in the MV group gradually decreased to lower than 7.20, while in the PLV group, pH also gradually decreased but remained higher than 7.20 (P < 0.05). Partial pressure of oxygen in artery (PaO2) decreased in both groups, but with a significant difference between the PLV group and MV group (P < 0.05). Partial pressure of carbon dioxide in artery (PaCO2) increased in both groups, but with a significant difference between the PLV group and MV group (P < 0.05). Paw increased in both groups, but was not significantly different (P > 0.05). Cydn decreased in both groups, but without a significant difference (P > 0.05). At four hours, heart rate (HR) and MAP in both groups decreased. MPAP in both groups increased, and there was a significant difference between the two groups (P < 0.05). CVP was stable in both groups. At four hours, PVR and LAP were increased in both groups. CO was decreased in both groups (P < 0.05). SVR was stable during the observation time. CONCLUSION: PLV did not improve outcome in changes of lung function.

Surgical closure of apical multiple muscular septal defects via right ventriculotomy using a single patch with intermediate fixings.

BACKGROUND: Multiple apical muscular ventricular septal defects (VSDs) remain a challenge for surgeons because of their anatomical features. We used single patch with intermediate fixations to repair multiple apical muscular VSDs through right ventriculotomy. METHODS: We analysed the data of 16 children (median age 8 months, range 2 months to 144 months) with multiple apical muscular VSDs who underwent a single patch technique via apical right ventriculotomy. Perioperative data were collected and analysed, and the patients were followed up for three months to 66 months (median, 46 months) to investigate the outcomes. RESULTS: All patients recovered from cardiopulmonary bypass easily with median of cardiopulmonary bypass time 87 minutes and of aortic crossclamp time 53 minutes. No surgically related death occurred and no patient required reoperation. One patient died of pseudomonas pyocyanea infection on day 11 postoperatively. Residual shunt happened in one patient with a diameter of 2 mm and spontaneously closed in 12 months after operation. Two patients presented slightly reduced right ventricular volume and apical hypokinesia postoperatively and recovered 24 and 36 months later respectively. No other complication was found during the three months to 66 months follow-up. CONCLUSION: Our experiences using a single patch technique with intermediate fixations via right ventriculotomy in the management of multiple muscular VSDs had favourable outcomes.

Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats.

BACKGROUND: Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS. METHODS: Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified. ALI was induced in rats byoleic acid (OA), and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection. RESULTS: The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge. CONCLUSIONS: Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

Angiotensin-converting enzyme 2 activation protects against pulmonary arterial hypertension through improving early endothelial function and mediating cytokines levels.

BACKGROUND: Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet. METHODS: Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established. RESULTS: Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis. CONCLUSIONS: These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines.