Expression of caveolin family proteins in serum of patients with systemic lupus erythematosus.

OBJECTIVES: Caveolin family proteins, including caveolin-1 (Cav-1), caveolin-2 (Cav-2), and caveolin-3 (Cav-3), are identified as the principal protein components of caveolae in mammalian cells. Circulating form of caveolin family proteins can be used as a good potential biomarker for predicting disease. METHODS: To investigate the clinical significance of the serological levels of caveolin family proteins in patients with systemic lupus erythematosus (SLE), we evaluated the soluble serum levels of caveolin family proteins in patients with SLE by enzyme-linked immunosorbent assay (ELISA) and assessed their associations with various known clinical variables. RESULTS: The major findings of our study are as follows: Cav-2 was not detected in serum of SLE patients and normal controls (NCs). Serum Cav-1 and Cav-3 levels were higher in SLE patients compared with NCs. There were no significant correlations between serum Cav-1 and Cav-3 levels and SLE disease activity. Further analysis showed that serum Cav-3 may be more valuable as a marker than serum Cav-1 in SLE patients. CONCLUSION: Serum levels of Cav-1 and Cav-3 might have a diagnostic role in patients with SLE. However, their predictive and prognostic value was not determined. Further studies are necessary to determine the potential clinical significance of these assays in SLE.

Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study.

BACKGROUND: Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process. AIM: To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes. METHODS: SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows-wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs. RESULTS: Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S). CONCLUSION: The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.

Disease-association of different killer cell immunoglobulin-like receptors (KIR) and HLA-C gene combinations in reactive arthritis.

BACKGROUND: Reactive arthritis (ReA) is sterile arthritis triggered by bacterial gastrointestinal or urogenital infections. Although the pathogenesis of ReA remains unclear, genetic factors seem to play an important role. Different killer cell immunoglobulin-like receptors (KIRs) and their corresponding specific histocompatibility leukocyte antigen-C (HLA-C) ligand genotypes have been implicated in susceptibility and resistance to infections and autoimmune diseases but have, thus far, not been investigated in ReA. METHODS: This study was conducted in 138 ReA patients (65 females, 73 males); aged 18-69 years (mean, 37 years) and 151 randomly selected healthy control individuals matched for ethnicity, age and sex. These subjects were genotyped for KIR genes and HLA-C alleles by polymerase chain reaction with sequence-specific primers. RESULTS: The frequencies of inhibitory KIR2DL2 and KIR2DL5 were significantly lower in the ReA patients than in the controls (p = .005 and p = .033, respectively). The presence of more than seven inhibitory KIR genes was protective (p = .016). Moreover, we found that activating KIR2DS1 alone or in combination with the HLA-C1C1 genotype (which indicates the absence of the HLA ligands for their homologous inhibitory receptor KIR2DL1) is associated with susceptibility to ReA (p = .039 and p = .011, respectively), whereas KIR2DL2 in combination with the HLA-C1 ligand is associated with protection against ReA (p = .039). CONCLUSION: These observations indicate that high levels of activating and low levels of inhibitory KIR signals may affect the functions of NK cells and T cells. This imbalance enables the innate and adaptive immune responses of the host to be easily triggered by pathogens, resulting in the overproduction of local and systemic cytokines that contribute to the pathogenesis of ReA.

Expression and clinical significance of the NEK7-NLRP3 inflammasome signaling pathway in patients with systemic lupus erythematosus.

BACKGROUND: The aim of the study was to investigate the expression of the NEK7-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance. METHODS: A total of 38 SLE patients and 33 healthy volunteers were recruited. Real time PCR and western blotting were performed to determine mRNA and protein levels of NEK7, NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and downstream cytokines (IL-1b and IL-18) in PBMCs from the two groups. ELISA was used to detect serum levels of IL-1b and IL-18. The same methods were used to detect changes in the above indices in the 25 SLE patients after treatment. Correlations between clinical and laboratory parameters were also analyzed. RESULTS: Compared to those in healthy controls, levels of NEK7, NLPR3, and ASC were lower in SLE patients; however, Caspase-1, IL-1b, and IL-18 were expressed at higher levels. mRNA levels of NEK7, NLRP3, and ASC were inversely correlated with disease activity, whereas a positive correlation was observed with IL-1b and IL-18. After treatment, mRNA levels of NEK7 and NLRP3 increased, whereas Caspase-1, IL-1b, and IL-18 decreased significantly. Compared to those in SLE patients without renal damage, patients with lupus nephritis (LN) exhibited lower mRNA levels of NEK7, NLRP3, and ASC but higher levels of Caspase-1, IL-1b, and IL-18. CONCLUSIONS: Results indicate that the expression of the NEK7-NLRP3 complex might play a protective role in the pathogenesis of SLE and is inversely correlated with disease activity. A positive effect of NEK7 on NLRP3 was observed, and the low expression of NLRP3 in SLE patients might be related to the low expression of NEK7. Overexpression of Caspase-1 in SLE patients mediates the maturation and release of IL-1b and IL-18, and contributes to the pathogenesis of SLE and LN.

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat.

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD.

Neuroprotective effects of cold-inducible RNA-binding protein during mild hypothermia on traumatic brain injury.

Cold-inducible RNA-binding protein (CIRP), a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5°C on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP mRNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury.

[Screening of Germination and Seedling Conditions of Trollius chinensis Seeds from Zhangjiakou].

Objective: To screen the germination and seedling conditions of Trollius chinensis seeds from Chongli county, Zhangjiakou city. To provide the theoretical basis and practical technology for establishing technology system of seedling and cultivation of Trollius chinensis seeds in Zhangjiakou city. Methods: The data were collected and analyzed by the contrast test of greenhouse. Results: The most suitable conditions of Trollius chinensis seedling treatment were as follows, the concentration of GA3 was 800 mg / m L at 4 ℃,and under this condition in infusing for 4 days, and placed in the artificial climate chamber, the temperature was 20 ℃,light treatment for 4 days with 12 h light and 12 h darkness, and sprayed PEG 6000( 30 g / L). Trollius chinesis seeds were sowed on the 4th day, peat soil was selected as matrix, and the germination rate reached more than 85%. Conclusion: According to the characteristics of the seedling appearance and the conditions of the seedlings after transplanting, the seedling growth is robust and the survival rate is much higher.

Expert consensus for postmarketing Chinese medicine intensive hospital safety monitoring.

It is of vital significance to conduct active postmarketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China Food and Drug Administration. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The expert consensus for postmarketing surveillance focuses on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.

[Technical specifications for intensive hospital safety monitoring of post-marketing Chinese medicine (draft version for comments)].

It is of vital significance to conduct active post-marketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China food and drug administration. The standards for technological specifications based on expert consensus have been drafted. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The technological specifications for post-marketing surveillance focus on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.

Diagnostic value of anti-Sa and anticitrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: To determine the diagnostic value of anticitrullinated protein antibodies, second generation (ACPA2), by electrochemiluminescent immunoassay (ECLIA) and anti-Sa by ELISA in a large cohort of Chinese patients with early rheumatoid arthritis (RA). METHODS: One hundred ninety-eight patients with early RA (< 1 yr duration), 112 with other rheumatic diseases, and 60 healthy individuals were studied. RESULTS: The combination of anti-Sa and ACPA2 positivity had the highest specificity (99.42%), but it had a rather low sensitivity (50.0%). The combination of anti-rheumatoid factor (RF) and ACPA2 showed the highest sensitivity (80.30%), with specificity of 95.93%. The mean titer of ACPA2 and RF was significantly higher in the anti-Sa-positive group compared to the negative group (ACPA2, p <0.001; RF, p = 0.007). The 28-joint Disease Activity Scores of the anti-Sa-positive patients were significantly higher than those of the negative group (p = 0.01). The anti-Sa had no significant correlation with age, sex, antinuclear antibody, SSA, SSB, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin A (IgA), IgG, IgM, C3, and C4. CONCLUSION: Our results come from a newly developed ECLIA for detection of ACPA2 and the anti-Sa-antibody-based ELISA system. The combined application of ACPA2 and anti-Sa tests can improve the laboratory diagnosis of early RA.

[Investigation on the title of bu mei (sleepless)].

There are various titles applied for "sleepless", including mu bu ming (unclosed eyes), bu de mian (unable to sleep), bu de wo (unable to lie down), shi mian (insomnia). The implications of the titles vary according to different periods. Bu de wo (unable to lie down) was first appeared in Zu bi shi yi mai jiu jing (Moxibustion Classic of Foot and Arm Eleven Channels) and Yin yang shi yi mai jiu jing (Moxibustion Classic of Yin-Yang Eleven Channels), while bu de wo, mu bu ming, and ye bu mei were appeared in Huang di nei jing (Inner Canon of Yellow Emperor), bu mei was first seen in Nan jing (Classic of Questioning). When bu de mian and bu de wo were applied in Zhang Zhongjing's Shang han lun (Treatise on Cold Pathogenic Diseases) and Jin kui yao lue (Synopsis of Golden Chamber), it exerted good influence in later generations. The title of bu mei was more popular after the Ming and Qing dynasties. This titles is the most appropriate one from the standpoint of syndrome itself as viewed from its semantic implication and its accuracy.