The incidence of hemorrhagic fever with renal syndrome (HFRS) in Qingdao, China was three times higher than that of the average national level. Here we characterized the epidemiology, ecological determinants and pathogen evolution of HFRS in Qingdao during 2007–2015. In this longitudinal study, a total of 1846 HFRS patients and 41 HFRS-related deaths were reported. HFRS in Qingdao peaked once a year in the fourth quarter. We built a time series generalized additive model, and found that meteorological factors in the previous quarter could accurately predict HFRS occurrence. To explore how meteorological factors influenced the epidemic of HFRS, we analyzed the relationship between meteorological factors and hantavirus-carrying states of the hosts (including rodents and shrews). Comprehensive analysis showed humidity was correlated to high host densities in the third quarter and high hantavirus-carrying rates of animal hosts in the third to fourth quarters, which might contribute to HFRS peak in the fourth quarter. We further compared the L segments of hantaviruses from HFRS patients, animal hosts and ectoparasites. Phylogenetic analysis showed that hantaviruses in gamasid and trombiculid mites were the same as those from the hosts. This indicated mites also contributed to the transmission of hantavirus. Furthermore, Hantaan virus from HFRS patients, hosts and mites in Qingdao formed a distinct phylogenetic cluster. A new clade of Seoul virus was also identified in the hosts. Overall, meteorological factors increase HFRS incidence possibly via facilitating hosts’ reproduction and consequent mite-mediated hantavirus transmission. New hantavirus subtypes evolved in Qingdao represent new challenges of fighting against HFRS.

Background/Aims: Mechanical loading plays an important role in the regulation of bone mass. However, bone cells are not always under physiological stress. In some cases, bone tissue is subjected to an overloaded mechanical environment. For example, a person who is weight training and a stevedore often experience bone pain, inflammation and other bone fatigue damage symptoms. Icariin is the major ingredient of Herba epimedii, which has been widely used for the treatment of bone injury in traditional Chinese medicine, but its mechanism remains unknown. The aim of this study was to probe the effect of icariin on the proliferation and differentiation of osteoblasts exposed to overload and to determine whether the Wnt/β-catenin signalling pathway is involved in the drug response in osteoblasts. Methods: Mouse MC3T3-E1 cells were exposed to mechanical tensile strain using a four- point bending device to create an overload damage model. An MTT assay was performed to determine the effects of icariin on MC3T3-E1 cell proliferation. The mRNA and protein levels of ALP, COL-I, OCN, RUNX2 and β-catenin were assessed using RT-PCR and immunoblotting. The protein levels of β-catenin in the MC3T3-E1 cells were also determined using fluorescence microscopy. The mineralization of osteoblasts was assessed using Alizarin Red S staining. Results: We found that icariin enhanced the proliferation of osteoblasts exposed to overload and promoted MC3T3-E1 cell differentiation and mineralization. Furthermore, the gene and protein expression levels of β-catenin and RUNX2 all increased with icariin treatment compared with those in the damage group. Conclusion: Our study suggested that icariin promotes proliferation and differentiation in osteoblasts exposed to overload. The effect of icariin on osteoblastic differentiation acted by activating the RUNX2 promoter and the Wnt/β- catenin pathway.

Hemorrhagic fever with renal syndrome (HFRS) was considered to be transmitted by Apodemus agrarius and Rattus norvegicus, the principal animal hosts of Hantaan virus and Seoul virus, respectively. The aim of this study is to determine the correlation of HFRS incidence with capture rate and hantavirus infection rate of rodent species in Qingdao City, China. We collected HFRS patients’ information and captured field and residential rodents in Qingdao City, China from 2010 to 2014. The correlations of HFRS incidence to rodent capture rate and hantavirus infection rate of rodents were analyzed statistically. The main findings of this study are that the high HFRS incidence (19.3/100,000) is correlated to the capture rate of field Mus musculus (p = 0.011, r = 0.037); but surprisingly it did not correlated to the capture rate of the principal rodent hosts Apodemus agrarius and Rattus norvegicus and the hantavirus infection rate of these rodent species in the field or residential area. These novel findings suggest that Mus musculus, a nontraditional animal host of hantavirus may play an important role in hantavirus transmission in Qingdao City.

Hand, foot, and mouth disease (HFMD) has caused public health concerns worldwide. We aimed to investigate the effect of meteorological factors on the HFMD epidemic in Qingdao, a port city in China. A total of 78641 cases were reported in Qingdao between January 2007 and December 2014. Of those, 71084 (90·39%) occurred in children aged 0-5 years, with an incidence of 1691·2/100000. The incidence increased from early spring, peaked between spring and summer, and decreased in late summer. Aetiological agents in all severe cases and selected mild cases were characterized by examining throat swabs. Except for enterovirus 71 (EV71) and coxsackievirus A16 (CA16), other EVs caused >50% of the HFMD cases between 2011 and 2014. EV71 was more frequent in the off-peak months than in the peak months and prone to causing more severe cases compared to CA16 (χ 2 = 46·3, P < 0·001). CA10 caused more severe HFMD than did CA6 (χ 2 = 20·49, P < 0·001) and all non-CA10 EVs (χ 2 = 41·01, P < 0·001). Community-derived HFMD cases accounted for 65·11%. Spearman rank correlation analysis showed that HFMD incidence in children aged 0-5 years was positively correlated with atmospheric temperature (r s = 0·77, P < 0·001), relative humidity (r s = 0·507, P < 0·001), and precipitation (r s = 0·328, P < 0·001). Climate changes and CA10 surveillance in communities should be integrated into the current prophylactic programme.