Chinese Central Government, the Ministry of Science and Technology of The People's Republic of China, and the National Natural Science Foundation of China.

ProblemChina continues to face challenges in eliminating mother-to-child transmission of human immunodeficiency virus (HIV), syphilis and hepatitis B virus (HBV).ApproachIn 2010, a programme that integrated and standardized prevention of mother-to-child transmission (PMTCT) efforts for HIV, syphilis and HBV was implemented in 1156 counties. At participating antenatal care clinics, pregnant women were offered all three tests concurrently and free of charge. Further interventions such as free treatment, prophylaxis and testing for mothers and their children were provided for HIV and syphilis.Local settingChina’s national PMTCT HIV programme started in 2003, at which time there were no national programmes for perinatal syphilis and HBV. In 2009, the rate of maternal-to-child transmission of HIV was 8.1% (57/702). Reported congenital syphilis was 60.8 per 100 000 live births. HBV infection was 7.2% of the overall population infected.Relevant changesBetween 2010 and 2013 the number of pregnant women attending antenatal care clinics with integrated PMTCT services increased from 5.5 million to 13.1 million. In 2013, 12.7 million pregnant women were tested for HIV, 12.6 million for syphilis and 12.7 million for HBV. Mother-to-child transmission of HIV fell to 6.7% in 2013. Data on syphilis transmission are not yet available.Lessons learntIntegrated PMTCT services proved to be feasible and effective, and they are now part of the routine maternal and child health services provided to infected women. The services are provided through a collaboration between maternal and child health clinics, the national and local Centers for Disease Control and Prevention, and general hospitals.

DNA-damaging reagents may kill tumor cells through the generation of reactive oxygen species (ROS). Cytotoxic reagents may also induce apoptosis of cancer cells in Fas-FADD-dependent manners. In this study, we explored the possible link between these two apparently distinct pathways in T leukemia cell Jurkat. Our results demonstrated that c-irradiation, similar to cisplatin, induced apoptosis by triggering Fas aggregation and activating FADDcaspase-8 apoptotic cascade. The absence of caspase-8 or Fas greatly reduced the sensitivity to apoptosis mediated by DNA-damaging agents. In addition, apoptosis induced by cisplatin and c-irradiation, but not by Fas, was inhibited by ROS scavengers, including N-acetyl cysteine, MnTBAP, and C 60 . Importantly, these ROS scavengers effectively prevented the clustering of Fas receptor induced by cisplatin and c-irradiation. Our results suggest that cisplatin and c-irradiation promote ROS production, which in turn contributes to Fas receptor aggregation and cell death. The novel coupling between ROS and Fas clustering likely plays a significant role in apoptosis triggered by DNA-damaging reagents in Fas-expressing leukemia cells.

Mesenchymal stem/stromal cells (MSCs) are promising potential candidates for the treatment of immunological diseases because of their immunosuppressive functions. However, the molecular mechanisms that mediate MSCs’ immunosuppressive activity remain elusive. In this article, we report for the first time, to our knowledge, that secreted growth-regulated oncogene (GRO) chemokines, specifically GRO-γ, in human MSC-conditioned media have an effect on the differentiation and the function of human monocyte-derived dendritic cells. The monocyte-derived dendritic cells were driven toward a myeloid-derived suppressor cell (MDSC)–like phenotype by the GRO chemokines. GRO-γ–treated MDSCs had a tolerogenic phenotype that was characterized by an increase in the secretion of IL-10 and IL-4, and a reduction in the production of IL-12 and IFN-γ. We have also shown that the mRNA expression levels of the arginase-1 and inducible NO synthase genes, which characterize MDSCs, were upregulated by GRO-γ–primed mouse bone marrow cells. In addition, the ability of GRO-γ–treated bone marrow–derived dendritic cells to stimulate the OVA-specific CD8+ T (OT-1) cell proliferation and the cytokine production of IFN-γ and TNF-α were significantly decreased in vivo. Our findings allow a greater understanding of how MDSCs can be generated and offer new perspectives to exploit the potential of MDSCs for alternative approaches to treat chronic inflammation and autoimmunity, as well as for the prevention of transplant rejection.

Variations in cervical cancer screening rates in China have rarely been studied in depth. This study aimed to investigate cervical cancer screening rates in relation to both individual‐level and geographical measures of socioeconomic status (SES). Data were obtained from women aged 21 years or older by face‐to‐face interviews between August 2013 and July 2014 as part of the Chinese Chronic Diseases and Risk Factors Surveillance. The geographical variables were obtained from the 2010 Chinese population census. The cervical cancer screening rates and 95% confidence interval (CI) were estimated and mapped. Multilevel logistic regression models were fitted. Overall, only 21.4% (95% CI: 19.6–23.1%) of 91,816 women aged ≥21 years reported having ever been screened for cervical cancer and significant geographical variations at both province and county levels were identified (P < 0.01). The cervical cancer screening rates were the lowest among the poor [13.9% (95% CI: 12.1–15.7%)], uninsured [14.4% (95% CI: 10.3–18.4%)], less‐educated [16.0% (95% CI: 14.3–17.6%)], and agricultural employment [18.1% (95% CI: 15.8–20.4%)] women along with those residing in areas of low economic status [15.0% (95% CI: 11.8–18.2%)], of low urbanization [15.6% (95% CI: 13.4–17.7%)], and of low education status [16.0% (95% CI: 14.0–18.1%)]. The multilevel analysis also indicated that women with lower individual‐level measures of SES residing in areas with low geographical measures of SES were significantly less likely to receive cervical cancer screening (P < 0.0001). Despite the launch of an organized cancer screening program in China, cervical cancer screening rates remain alarmingly low and significant variations based on geographical regions and measures of SES still exist. It is therefore essential to adopt strategies to better direct limited available public resources to priority groups.

Phloretin (PT), isolated from the apple tree, was previously demonstrated to have antioxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species (ROS) for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether PT could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three PT doses (5, 10, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with PT to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that PT significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. PT also decreased malondialdehyde levels in the lung and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, PT reduced ROS, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. PT also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that PT alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. PT showed therapeutic potential for ameliorating asthma symptoms in the future.

Death-associated protein kinase (DAPK) is a unique multidomain kinase acting both as a tumor suppressor and an apoptosis inducer. The molecular mechanism underlying the effector function of DAPK is not fully understood, while the role of DAPK in T lymphocyte activation is mostly unknown. DAPK was activated after TCR stimulation. Through the expression of a dominant-negative and a constitutively active form of DAPK in T cells, we found that DAPK negatively regulated T cell activation. DAPK markedly affected T cell proliferation and IL-2 production. We identified TCR-induced NF-kappaB activation as a target of DAPK. In contrast, IL-1beta- and TNF-alpha-triggered NF-kappaB activation was not affected by DAPK. We further found that DAPK selectively modulated the TCR-induced translocation of protein kinase Ctheta, Bcl-10, and IkappaB kinase into membrane rafts. Notably, the effect of DAPK on the raft entry was specific for the NF-kappaB pathway, as other raft-associated molecules, such as linker for activation of T cells, were not affected. Our results clearly demonstrate that DAPK is a novel regulator targeted to TCR-activated NF-kappaB and T cell activation.

No abstract