[Recommendations for the diagnosis and treatment of rheumatic fever in China].

Rheumatic fever is an autoimmune disease characterized by recurring acute or chronic systemic connective tissue inflammation caused by group A streptococcal infection in the throat. Although rheumatic fever is common in China, there is a lack of standardized criteria for the diagnosis and treatment of this condition. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association developed standardized criteria for the diagnosis and treatment of this disease in China. The aim was to standardize rheumatic fever diagnosis methods, treatment opportunities, and strategies for both short-and long-term treatment, so as to reduce irreversible damage and improve prognosis.

Pressure-Induced Superconductivity up to 9 K in the Quasi-One-Dimensional KMn_{6}Bi_{5}.

The Mn-based superconductor is rare owing to the strong magnetic pair-breaking effect. Here we report on the discovery of pressure-induced superconductivity in KMn_{6}Bi_{5}, which becomes the first ternary Mn-based superconductor. At ambient pressure, the quasi-one-dimensional KMn_{6}Bi_{5} is an antiferromagnetic metal with T_{N}≈75 K. By measuring resistance and ac magnetic susceptibility under hydrostatic pressures up to 14.2 GPa in a cubic anvil cell apparatus, we find that its antiferromagnetic transition can be suppressed completely at a critical pressure of P_{c}≈13 GPa, around which bulk superconductivity emerges and displays a superconducting dome with the maximal T_{c}^{onset}=9.3 K achieved at about 14 GPa. The close proximity of superconductivity to a magnetic instability in the temperature-pressure phase diagram of KMn_{6}Bi_{5} and an unusually large µ_{0}H_{c2}(0) exceeding the Pauli paramagnetic limit suggests an unconventional magnetism-mediated paring mechanism. In contrast to the binary MnP, the flexibility of the crystal structure and chemical compositions in the ternary AMn_{6}Bi_{5} (A=alkali metal) can open a new avenue for finding more Mn-based superconductors.

Inhibition of osteoclast differentiation and matrix metalloproteinase production by CD4+CD25+ T cells in mice.

UNLABELLED: To reveal the mechanism of inflammation-accompanied osteoporosis, mouse CD11b cells and CD4+CD25+ T cells were cocultured. Our results showed that CD11b+ monocytes cocultured with CD4+CD25+ T cells generated significantly less osteoclasts than those cocultured with CD4+CD25- T cells. The levels of MMP-7 and 9 in coculture supernatant were decreased significantly when CD11b+ monocytes and CD4+CD25+ T cells were cocultured comparing to the CD4+CD25- T cell group. These results highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis. INTRODUCTION: The purpose of this study was to reveal the mechanism of inflammation-accompanied osteoporosis by examining the effect of CD4+CD25+ T cells on osteoclast formation, as well as the production of matrix metalloproteinases (MMP)-2, 3, 7, and 9 from osteoclasts. METHODS: Mouse CD11b cells and CD4+CD25+ T cells were isolated using the microbead-based kits. Activated CD11b cells and CD4+CD25+ T were cocultured. CD4+CD25- T cells were used as controls. Osteoclasts were evaluated by counting the average of tartrate-resistant acid phosphatase-positive multinucleated large cells among five high-power fields (×200). After 2 days of coculture, supernatants were harvested for MMP measurement (by ELISA). RESULTS: At day 7, the CD11b+ monocytes cocultured with CD4+CD25+ T cells generated significantly (both p < 0.01) less osteoclasts (3.4 ± 0.8) than those cocultured with CD4+CD25- T cells (16.2 ± 1.3) and those cultured alone (16.2 ± 2.7). The supernatant levels of MMP-7 and 9 were decreased significantly (p < 0.01) when CD11b+ monocytes and CD4+CD25+ T cells were cocultured compared to the other two conditions. CONCLUSIONS: The decreased CD4+CD25+ T cells may cause an overproduction of MMP-7 and 9 from osteoclasts, which highlight the role of CD4+CD25+ T cells on rheumatic osteoporosis.

Pressured-induced superconducting phase with large upper critical field and concomitant enhancement of antiferromagnetic transition in EuTe2.

We report an unusual pressure-induced superconducting state that coexists with an antiferromagnetic ordering of Eu2+ moments and shows a large upper critical field comparable to the Pauli paramagnetic limit in EuTe2. In concomitant with the emergence of superconductivity with Tc ≈ 3-5 K above Pc ≈ 6 GPa, the antiferromagnetic transition temperature TN(P) experiences a quicker rise with the slope increased dramatically from dTN/dP = 0.85(14) K/GPa for P ≤ Pc to 3.7(2) K/GPa for P ≥ Pc. Moreover, the superconducting state can survive in the spin-flop state with a net ferromagnetic component of the Eu2+ sublattice under moderate magnetic fields µ0H ≥ 2 T. Our findings establish the pressurized EuTe2 as a rare magnetic superconductor possessing an intimated interplay between magnetism and superconductivity.

An approach to structural facial rejuvenation with fillers in women.

Newer understanding of volume loss as a critical component of facial aging and the integration of volume replacement into the surgical and nonsurgical therapeutic algorithm is arguably the most significant recent development in the field of facial rejuvenation. As all structural tissues play a role in the aging face, restoring youthful characteristics (or establishing them where they are congenitally absent) starts from the skeletal framework and builds progressively to the canvas of the face. The purpose of this article is to provide an introduction and brief summary of some of the current concepts concerning facial anatomy and the anatomy of facial aging, which serve as the basis for predictable and reproducible results with the use of injectable fillers. This article does not include the various types of fillers or techniques of filler injection, but covers how to decide where to use the filler and why, in different faces, as a result of the recognition and targeted correction of currently recognized specific anatomic deficiencies.

Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis.

Clinically amyopathic dermatomyositis (CADM) is a unique subset of dermatomyositis, showing a high incidence of lung involvements. The aim of this study is to identify risk factors, other than melanoma differentiation-associated protein (MDA)-5, for developing rapidly progressive-interstitial lung disease (RP-ILD) in patients with CADM. Forty CADM patients, in whom 11 patients developed RP-ILD, were enrolled. Clinical features and laboratory findings were compared between the patients with and without RP-ILD. We found that skin ulceration, CRP, serum ferritin, anti-MDA5 Ab, and lymphocytopenia were significantly associated with ILD. Multivariate logistic regression analysis indicated that anti-MDA5 Ab(+), elevated CRP, and decreased counts of lymphocyte were independent risk factors for RP-ILD, which can provide a precise predict for RP-ILD in CADM patients. When anti-MDA5 Ab(+) was removed from the multivariate regression model, using skin ulcerations, elevated serum ferritin and decreased counts of lymphocyte can also precisely predict RP-ILD. Except for MDA-5, more commonly available clinical characteristics, such as skin ulcerations, serum ferritin, and count of lymphocyte may also help to predict prognosis in CADM.

Effects of beta-adrenergic stimulation on atrial latency and atrial vulnerability in patients with paroxysmal supraventricular tachycardia.

To assess the effects of beta-adrenergic stimulation on atrial latency and atrial vulnerability, the electrophysiologic properties of the atrium were studied before and during intravenous infusion of isoproterenol at 2 to 5 micrograms/min in 11 patients with paroxysmal supraventricular tachycardia exhibiting atrial latency during programmed atrial extrastimulation. In all patients, the isoproterenol infusion reduced the extent of maximum atrial latency (from 86 +/- 19 to 62 +/- 16 ms, p less than 0.001). This was accompanied by a significant shortening of both effective and functional refractory periods of the atrium (from 213 +/- 31 to 174 +/- 40 ms, p less than 0.005 and from 259 +/- 31 to 215 +/- 29 ms, p less than 0.001, respectively). The intra-atrial and interatrial conduction times were also significantly reduced (from 24 +/- 15 and 63 +/- 17 to 15 +/- 10 and 48 +/- 15 ms, p less than 0.005, respectively). In 3 patients with demonstrable atrial vulnerability, the isoproterenol infusion abolished the inducibility of repetitive atrial responses or atrial flutter, or both. Although the clinical significance of the suppressive action of beta-adrenergic stimulation on atrial vulnerability remains to be determined, the present study has demonstrated that beta-adrenergic stimulation significantly reduces atrial latency.

Paraganglioma complicating pregnancy and the puerperium.

A rare case of a paraganglioma (extraadrenal pheochromocytoma) that complicated both pregnancy and the puerperium is described. The patient presented a confusing clinical picture simulating pregnancy-induced hypertension, which, after delivery, masqueraded as intractable fever of unknown origin. Computed tomography precisely identified the presence and location of the mass, which had eluded detection despite exhaustive testing. Pheochromocytoma should be considered in the differential diagnosis of postpartum fever of unknown origin, especially if associated with paroxysmal hypertension.

WNT7B mediates autocrine Wnt/ß-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma.

Developmental and cancer models show Wnt/ß-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/ß-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/ß-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/ß-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally generated, pancreas-specific gene expression signature of Wnt/ß-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early-stage PDAC tumors (N=41). In this cohort, higher Wnt/ß-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease-specific survival (median survival time 20.3 versus 43.9 months, log-rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/ß-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small-molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/ß-catenin activity. Gene-knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B-mediated cell autonomous Wnt/ß-catenin activation, as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/ß-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/ß-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members.

Abdominal compartment syndrome complicating paediatric extracorporeal life support: diagnostic and therapeutic challenges.

We report three paediatric cases, and summarise the reported experience in two others, with cardiorespiratory failure requiring extracorporeal life support for which supportive pump flows could not be maintained due to abdominal compartment syndrome. In two of our patients, the mechanism of abdominal compartment syndrome was massive intra-abdominal fluid extravasation secondary to sepsis, while in the third, the mechanism was post-traumatic intra-abdominal haemorrhage. Although all three children eventually died, decompressive laparotomy and arrest of haemorrhage in the trauma patient restored venous return and enabled technically adequate extracorporeal life support. In two previously reported cases of sepsis with massive fluid resuscitation resulting in abdominal compartment syndrome, one patient died without attempted decompression, while the other patient survived after peritoneal catheter placement restored venous return. Once correctable causes of inadequate venous cannula drainage have been excluded, abdominal compartment syndrome should be considered in any patient on extracorporeal life support with a taut abdomen and reduced venous return. If abdominal compartment syndrome can be proven or is strongly suspected, there may be a role for selective decompressive laparotomy.

Organ-specific toxicokinetics and dose-response of arsenic in tilapia Oreochromis mossambicus.

We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)-based acute toxicity model and a pharmacodynamic model to derive dose-response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)-time-response relationships, which can also be applied to predict a time-mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC50(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC50 and incipient LC50 for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L(-1), respectively. Dose-response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC50. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC50 were 26.6, 62.5, and 78.5 microg g(-1) dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.

Increased CCR4 expression on circulating CD4(+) T cells in ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus.

Previous studies have suggested that CCR4 is particularly important in the selective recruitment of various subsets of leucocytes in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we examined the percentage of CD4(+)/CCR4(+) T cells within circulating lymphocytes in active ankylosing spondylitis (AS), RA and SLE patients. The clinical significance of CCR4 expression as well as possible associations between the expression and serum levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 were also examined. Our results showed that the percentage of CD4(+)/CCR4(+) T cells was significantly elevated in AS and RA patients as compared with normal controls. The percentage was also significantly higher in SLE patients who had received no treatment with glucocorticoids or cytotoxic drugs (untreated SLE) than that in controls. In addition, the percentage of CD4(+)/CCR4(+) T cells showed significant positive correlations with the Bath ankylosing spondylitis disease activity index (BASDAI) in AS and with the SLE disease activity index (SLEDAI) in untreated SLE. Of all the cytokines examined, the elevated serum IL-10 level was closely correlated with the percentage of CD4(+)/CCR4(+) T cells in AS, RA and untreated SLE. These results suggest that CCR4 may be crucial in the pathogenesis of AS, RA and SLE. The percentage of CD4(+)/CCR4(+) T cells can serve as a useful marker for the activity of AS and untreated SLE.

IL-12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll-like Receptor (TLR).

Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various well-documented medicinal properties. In the present study, we investigated the effects of hemicellulase-derived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine-inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL-12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL-12 production by the CD14-positive cell population, consisting of monocytes/macrophages (Mo/Mphi). Furthermore, the elimination of Mo/Mphi attenuated IL-12 production in PBMC. ABH-induced IL-12 production was inhibited by anti-CD14 and anti-TLR4 antibodies but not by anti-TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mphi in a manner dependent on CD14/TLR4 and NK activity.