Cytomegalovirus Infection May Trigger Adult-Onset Still's Disease Onset or Relapses

Previous studies have revealed that several micro-organisms, especially DNA viruses, have been associated with adult-onset Still's disease (AOSD). However, there are no studies on the relationship between the presence of viral infections in AOSD patients with disease occurrence and reactivation. In the present study, we aimed to investigate the presence of antibodies against virus, virus DNA load and nucleic acid sensors in AOSD patients. Anti-viral antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples from 100 AOSD patients and 70 healthy controls (HCs). The copy number of cytomegalovirus (CMV) DNA in 100 AOSD patients was detected by PCR. The expression levels of nucleic acid sensors interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) in peripheral blood mononuclear cell (PBMC) and skin from AOSD patients and HCs were analyzed by PCR and immunohistochemistry. The levels of antibodies against CMV were significantly higher in AOSD patients compared to HCs. Moreover, the level of anti-CMV IgM antibody was significantly increased in patients with fever, sore throat, arthralgia and rash. CMV DNA was found in plasma of AOSD patients with disease new-onset and relapse. Furthermore, the copy number of CMV DNA significantly increased in patients with fever, sore throat, arthralgia and rash. And the significant associations of the CMV DNA level with the levels of leukocytes, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were observed. Moreover, we found an upregulation of cytoplasmic DNA-sensing receptor IFI16 and AIM2 in PBMC and skin from AOSD patients. In conclusion, our results showed that CMV infection may play a role in the initiation or amplification of inflammatory responses in AOSD

Intimacy and Intergenerational Relations in Rural China

This article applies the concept of intimacy to examine relationships between adult children and their parents in rural China – an area which has been predominantly located in an obligatory framework. I reveal a qualitative difference in support between relationships built on intimate ties and those bound by duty and obligation. A unilateral emphasis on obligation-based relationships can deprive both the parent and adult child generations of agency and autonomy, which can be disempowering for both. The complex relations between intimacy and obligation are the product of local socio-economic circumstances and gender norms. Although traditional patrilineal and patrilocal culture excludes married daughters from the filial discourse surrounding their own parents, they are often considered to have the most intimate relationship with their parents. Paradoxically, the practices of intimacy between aged parents and their married daughters strengthen the natal ties that facilitate modifications to patrilocal and patrilineal customs

The role of platelet-derived molecules: PDGF and serotonin in the regulation of megakaryopoiesis

Investigations on platelet-derived growth factor (PDGF) and serotonin (5-HT), molecules stored in platelet granules, imply their potential effects in regulating megakaryopoiesis, which also intimates the existence of an autocrine and/or paracrine loop constructed by megakaryocytes/platelets and their granular constituents. In addition, numerous reports indicate that melatonin, a derivative from serotonin effectively enhances platelet counts in patients with thrombocytopenia. However, their exact roles on human megakaryocytes and the underlying mechanisms remain unknown. Present studies showed that PDGF, like thrombopoietin (TPO), significantly promoted platelet recovery and the formation of bone marrow colony-forming unit-megakaryocyte (CFU-MK) in an irradiated-mouse model. An increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis were found in the bone marrow aspirate. In the M-07e apoptotic model, PDGF had a similar anti-apoptotic effect as TPO on megakaryocytes. Our findings demonstrated that PDGF activated the PI3-k/Akt signaling pathway, while addition of imatinib mesylate reduced p-Akt expression. Our findings suggested that the PDGF-initiated radioprotective effect is likely to be mediated via PDGF receptors (PDGFRs) with subsequent activation of the PI3-k/Akt pathway. We also provide a possible explanation that blockade of PDGFR may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia. We explored how serotonin regulated megakaryopoiesis and proplatelet formation. Our results indicated that serotonin (5-HT) significantly promoted CFU-MK formation and reduced apoptosis on megakaryocytes through phosphorylation of Akt. These effects were attenuated by addition of ketanserin, a 5-HT2 receptor inhibitor. In addition, serotonin was able to stimulate the F-actin reorganization in megakaryocytes through activating the p-Erk1/2 expression. Bone marrow mesenchymal stromal cells (MSCs) are important in regulating megakaryopoiesis through stimulating the release of thrombopoietic growth factor, such as TPO. Our studies suggested that when activated by serotonin, bone marrow MSCs were induced to release significant amount of TPO. Furthermore, thousands of membrane-derived microparticles (MPs) arose from MSCs and the TPO RNA/proteins contained within MPs were also considerably increased under serotonin treatment. In summary, our findings demonstrated an important role serotonin played on megakaryopoiesis. This effect was likely mediated via 5HT2 receptors with subsequent activation of Akt and Erk 1/2 phosphorylation, which led to survival of megakaryocytes and proplatelet formation. Serotonin also stimulated TPO released from MSCs in both dissociative and MP-encapsulated form, which indirectly promoted megakaryopoiesis. The effects of melatonin on megakaryopoiesis were also determined in our studies. Our findings showed that melatonin enhanced proliferation and reduced doxorubicin-induced toxicity on MKs. We further demonstrated the mechanism for melatonin-mediated protection on MKs maybe via repair of G2/M phase cell cycle arrest and inhibition of cell apoptosis on MK cells. The effects of melatonin on megakaryopoiesis were also determined in our studies. Our findings showed that melatonin enhanced proliferation and reduced doxorubicin-induced toxicity on MKs. We further demonstrated the mechanism for melatonin-mediated protection on MKs maybe via repair of G2/M phase cell cycle arrest and inhibition of cell apoptosis on MK cells.published_or_final_versionPaediatrics and Adolescent MedicineDoctoralDoctor of Philosoph

A Nonparametric Model for Multi-Manifold Clustering with Mixture of Gaussians and Graph Consistency

Multi-manifold clustering is among the most fundamental tasks in signal processing and machine learning. Although the existing multi-manifold clustering methods are quite powerful, learning the cluster number automatically from data is still a challenge. In this paper, a novel unsupervised generative clustering approach within the Bayesian nonparametric framework has been proposed. Specifically, our manifold method automatically selects the cluster number with a Dirichlet Process (DP) prior. Then, a DP-based mixture model with constrained Mixture of Gaussians (MoG) is constructed to handle the manifold data. Finally, we integrate our model with the k-nearest neighbor graph to capture the manifold geometric information. An efficient optimization algorithm has also been derived to do the model inference and optimization. Experimental results on synthetic datasets and real-world benchmark datasets exhibit the effectiveness of this new DP-based manifold method

Correlation between reproductive factors and thyroid nodules in postmenopausal women

Objective To explore the correlation of reproductive factors with thyroid nodules (TNs) in postmenopausal women in Lanzhou, Gansu Province so as to provide reliable strategies for the prevention and treatment of TNs. Methods A total of 2 270 postmenopausal female residents aged 43 and over living in Tianqingjiayuan, Guangwumen and Xicun Street Communities for longer than 5 years in Lanzhou from 2014 to 2016 were recruited as the research objects. The data of menarche age, menopausal age, time of pregnancy, time of delivery, time of abortion and pregnancy complications were surveyed and collected through questionnaires. Thyroid ultrasound examination was performed. Multivariate logistic regression analysis was used to explore the correlation between female reproductive factors and TNs. Results The prevalence of TNs was 60.97% (1 384/2 270) in postmenopausal women in Lanzhou, and the prevalence was increased gradually with the increase of age (Chi-squaretrend=66.761, P<0.001). The patients in the TNs group had significantly older age, larger proportions of non-higher education level, hypertension, diabetes and smoking, higher levels of WC, HC, SBP, FBG, 2hPG, HbA1c, TG, Crea and UA levels, and lower HDL-C, TSH, FT3, TGAb and TPOAb levels when compared with those in the non-TNs group. The prevalence of TNs was increased obviously with the increase of times of pregnancy and childbirth and older menopausal age (time of pregnancies: Chi-squaretrend=11.874, P=0.001; time of delivery: Chi-squaretrend=37.385, P<0.001; menopausal age: Chi-squaretrend=8.897, P=0.003). Multivariate logistic regression analysis showed that the risk of nodules was increased for those with postmenopausal age over 55 years than those with the age <45 years (OR=2.372, 95%CI: 1.142~4.926, P=0.021). No notable correlation was observed in menarche age, abortion times, ectopic pregnancy, contraceptive/estrogen history, macrosomia, pregnancy complications, breastfeeding, menopausal type and other factors with TNs. Conclusion The prevalence of TNs is quite high in menopausal women in Lanzhou, which is affected by many factors. Among them, the delayed menopausal age is a high-risk factor for the prevalence. Therefore, we should focus on strengthening the thyroid ultrasound examination of perimenopausal women, so as to find the existence early for early intervention