These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed.

Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle (C t ) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Navβ1, Navβ3, Cav1.3, Cav3.1 and Cavα2δ2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cavβ2 and Cavγ4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvβ1, MinK and Cavγ7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart.

The majority of Na + channels in the heart are composed of the tetrodotoxin (TTX)-resistant (K D , 2-6 µM) Na v 1.5 isoform; however, recently it has been shown that TTX-sensitive (K D , 1-10 nM) neuronal Na + channel isoforms (Na v 1.1, Na v 1.3 and Na v 1.6) are also present and functionally important in the myocytes of the ventricles and the sinoatrial (SA) node. In the present study, in mouse SA node pacemaker cells, we investigated Na + currents under physiological conditions and the expression of cardiac and neuronal Na + channel isoforms. We identified two distinct Na + current components, TTX resistant and TTX sensitive. At 37• C, TTX-resistant i Na and TTX-sensitive i Na started to activate at ∼ −70 and ∼ −60 mV, and peaked at −30 and −10 mV, with a current density of 22 ± 3 and 18 ± 1 pA pF −1 , respectively. TTX-sensitive i Na inactivated at more positive potentials as compared to TTX-resistant i Na . Using action potential clamp, TTX-sensitive i Na was observed to activate late during the pacemaker potential. Using immunocytochemistry and confocal microscopy, different distributions of the TTX-resistant cardiac isoform, Na v 1.5, and the TTX-sensitive neuronal isoform, Na v 1.1, were observed: Na v 1.5 was absent from the centre of the SA node, but present in the periphery of the SA node, whereas Na v 1.1 was present throughout the SA node. Nanomolar concentrations (10 or 100 nM) of TTX, which block TTX-sensitive i Na , slowed pacemaking in both intact SA node preparations and isolated SA node cells without a significant effect on SA node conduction. In contrast, micromolar concentrations (1-30 µM) of TTX, which block TTX-resistant i Na as well as TTX-sensitive i Na , slowed both pacemaking and SA node conduction. It is concluded that two Na + channel isoforms are important for the functioning of the SA node: neuronal (putative Na v 1.1) and cardiac Na v 1.5 isoforms are involved in pacemaking, although the cardiac Na v 1.5 isoform alone is involved in the propagation of the action potential from the SA node to the surrounding atrial muscle.

Morbidity attributed to the five defined cardiovascular risk factors was high in the Chinese population, with multiple risk factors present in the same individual. Therefore, reasonable prevention strategies should be designed to attenuate the rapid rise in cardiovascular morbidity.

BackgroundThe importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized.MethodsData from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated.FindingsCryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative.ConclusionsThe enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.