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1.  Outbreak of Epidemic Keratoconjunctivitis Caused by Human Adenovirus Type 56, China, 2012 
PLoS ONE  2014;9(10):e110781.
HAdV-56 is a new recombinant type isolated from epidemic keratoconjunctivitis (EKC) patients and has been sporadically isolated in Japan several times. Here, an outbreak of EKC in the city of Dalian, China involving a large number of workers in two factories was reported; this was the first outbreak of EKC associated with HAdV-56 worldwide.
PMCID: PMC4208770  PMID: 25343525
2.  Evaluation of the effects of comprehensive reform on primary healthcare institutions in Anhui Province 
In 2009, the Chinese Central Communist Party and the China State Council started to implement comprehensive healthcare reforms. The first round of reforms, involving Anhui province, was from 2009 to 2011, and focused on primary healthcare institutions. This study conducts an initial assessment of the effects of specific parts of the reforms in Anhui.
Mixed quantitative and qualitative methods were adopted for data collection. Seven hundred and three health institutions from 15 counties were randomly chosen. The practices, development, effects, problems, and other relevant information related to the reform were classified into four aspects: medicine management; personnel systems and income distribution mechanisms; compensation mechanisms for primary healthcare institutions; and strengthening the primary healthcare system. The effects of reform were analyzed by evaluating changes in compensation channels, visit costs, diagnosis and treatment structure, hardware, structures, efficiency, and behavior.
A new system for authorizing drugs resulted in a total of 857 new drugs being accessible at agreed prices through primary healthcare institutions in Anhui. The cost of the average outpatient visit decreased from 35.29 RMB to 31.64 RMB, although for inpatients, the average cost increased from 799.05 RMB to 992.60 RMB. The number of healthcare personnel decreased, but their workloads increased. The total revenue from government sources increased by 41.09%, and the proportion of revenue from drugs decreased by 25.19%. The rate of diagnosis and treatment visits and outpatient visits to primary healthcare institutions increased. Finally, between 2008 and 2010, 1,195 standardized township hospitals, 14,134 village clinics, and 1,234 community health service institutions were constructed.
The reform of primary healthcare institutions in Anhui has improved the personnel structures surrounding frontline healthcare workers, increased their incomes, improved work efficiency, and changed the compensation patterns of primary healthcare institutions, improved hardware, reduced drug prices, and, to some extent, improved the diagnosis and treatment structure. However, the reforms have not radically changed the behavior of medical workers or the visit patterns of patients. Approaches such as strengthening performance evaluation, and carrying out initiatives to further mobilize frontline healthcare workers, enhance rational drug use through improved training and educate patients, should be undertaken in the future.
PMCID: PMC4105389  PMID: 24942901
Health reform; Primary healthcare institutions; Anhui province
3.  SPX1 is an important component in the phosphorus signalling network of common bean regulating root growth and phosphorus homeostasis 
Journal of Experimental Botany  2014;65(12):3299-3310.
PvSPX1 was found to be a positive regulator in the P signalling network of common bean, and is downstream of PvPHR1.
Proteins containing the SPX domain are believed to play vital roles in the phosphorus (P) signalling network in plants. However, the functions of SPX proteins in legumes remain largely unknown. In this study, three SPX members, PvSPX1–PvSPX3 were cloned from common bean (Phaseolus vulgaris L.). It was found that the transcripts of all three PvSPX members were significantly enhanced in both bean leaves and roots by phosphate (Pi) starvation. Among them, the expression of nuclear localized PvSPX1 showed more sensitive and rapid responses to Pi starvation. Consistently, only overexpression of PvSPX1 resulted in increased root P concentration and modified morphology of transgenic bean hairy roots, such as inhibited root growth and an enlarged root hair zone. It was further demonstrated that PvSPX1 transcripts were up-regulated by overexpressing PvPHR1, and overexpressing PvSPX1 led to increased transcripts of 10 Pi starvation-responsive genes in transgenic bean hairy roots. Taken together, it is suggested that PvSPX1 is a positive regulator in the P signalling network of common bean, and is downstream of PvPHR1.
PMCID: PMC4071846  PMID: 24790114
Bean; hairy roots; phosphate starvation; phosphorus homeostasis; root growth; SPX domain.
4.  Gender differences in the development of uremic cardiomyopathy following partial nephrectomy: Role of progesterone 
Journal of hypertension : open access  2013;2:10.4172/2167-1095.1000109.
Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed competitive inhibition of cardiotonic steroid binding to Na/K-ATPase and partially inhibited collagen synthesis induced by marinobufagenin in cultured cardiac fibroblasts. Therefore, we sought to examine whether female rats displayed less uremic cardiomyopathy than male rats when subjected to partial nephrectomy. Although partial nephrectomy caused the induction of smaller increases in blood pressure of female rats, they appeared to be similarly susceptible to cardiac remodeling induced by partial nephrectomy in terms of hypertrophy and fibrosis as age-matched male rats. The possible explanations for our findings are therefore discussed.
PMCID: PMC3880896  PMID: 24404431
Uremic cardiomyopathy; Renal failure; Cardiotonic steroids; Collagen; Fibrosis; Progesterone; Gender
5.  Ouabain-Stimulated Trafficking Regulation of the Na/K-ATPase and NHE3 In Renal Proximal Tubule Cells 
Molecular and cellular biochemistry  2012;367(1-2):175-183.
We have demonstrated that ouabain regulates protein trafficking of the Na/K-ATPase α1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this mechanism is species-specific, ouabain-induced regulation of the α1 subunit and NHE3 as well as transcellular 22Na+ transport were compared in three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 in which the pig α1 was replaced by ouabain-resistant rat α1). Ouabain inhibited transcellular 22Na+ transport due to an ouabain-induced redistribution of the α1 subunit and NHE3. In LLC-PK1 cells, ouabain also inhibited the endocytic recycling of internalized NHE3, but has no significant effect on recycling of endocytosed α1 subunit. These data indicated that the ouabain-induced redistribution of the α1 subunit and NHE3 is not a species-specific phenomenon, and ouabain-activated Na/K-ATPase signaling influences NHE3 regulation.
PMCID: PMC3475650  PMID: 22618525
Ouabain; Na/K-ATPase signaling; Na/K-ATPase; NHE3; redistribution
6.  A novel hemostatic sealant composed of gelatin, transglutaminase and thrombin effectively controls liver trauma-induced bleeding in dogs 
Acta Pharmacologica Sinica  2013;34(7):983-988.
A novel hemostatic sealant based on the in situ gel formation of gelatin catalyzed by thrombin and crosslinked by transglutaminase was designed. The aim of this study was to investigate the efficacy of the hemostatic sealant in control of bleeding caused by liver trauma in dogs.
Hepatic trauma that mimicked the grade III–IV rupture of liver was made in 20 dogs. The traumatic lesion was topically administered the hemostatic sealant (treatment group, n=10), or a thrombin solution (control group, n=10). The time to achieve hemostasis and the blood loss were measured. Contrast-enhanced ultrasound (CEUS) examination was performed in each animal on d 3, d 7, and d 10 d postoperatively to study the healing of the lesions.
The mean time to achieve hemostasis in the treatment group was significantly shorter than that in the control group (1.20±0.33 vs 6.70±0.64 min, P<0.05). The mean blood loss in the treatment group was significantly less than that in the control group (47.22±8.61 vs 79.29±11.97 mL, P<0.05). In CEUS examination, the traumatic lesions in the treatment group became significantly smaller on d 3, and disappeared on d 7, whereas the lesions in the control group still existed on d 10. Ascites were never found during 10 d follow-up in the treatment group but were observed on d 3 and d 7 in the control group.
Compared with thrombin, the novel hemostatic sealant shows much better efficacy in hemostasis and may promote wound healing in dog liver trauma.
PMCID: PMC4002607  PMID: 23645012
liver; trauma; hemostatic; transglutaminase; gelatin; thrombin
7.  Comparative Analysis of PvPAP Gene Family and Their Functions in Response to Phosphorus Deficiency in Common Bean 
PLoS ONE  2012;7(5):e38106.
Purple acid phosphatases (PAPs) play a vital role in adaptive strategies of plants to phosphorus (P) deficiency. However, their functions in relation to P efficiency are fragmentary in common bean.
Principal Findings
Five PvPAPs were isolated and sequenced in common bean. Phylogenetic analysis showed that PvPAPs could be classified into two groups, including a small group with low molecular mass, and a large group with high molecular mass. Among them, PvPAP3, PvPAP4 and PvPAP5 belong to the small group, while the other two belong to the large group. Transient expression of 35S:PvPAPs-GFP on onion epidermal cells verified the variations of subcellular localization among PvPAPs, suggesting functional diversities of PvPAPs in common bean. Quantitative PCR results showed that most PvPAPs were up-regulated by phosphate (Pi) starvation. Among them, the expression of the small group PvPAPs responded more to Pi starvation, especially in the roots of G19833, the P-efficient genotype. However, only overexpressing PvPAP1 and PvPAP3 could result in significantly increased utilization of extracellular dNTPs in the transgenic bean hairy roots. Furthermore, overexpressing PvPAP3 in Arabidopsis enhanced both plant growth and total P content when dNTPs were supplied as the sole external P source.
The results suggest that PvPAPs in bean varied in protein structure, response to P deficiency and subcellular localization. Among them, both PvPAP1 and PvPAP3 might function as utilization of extracellular dNTPs.
PMCID: PMC3360649  PMID: 22662274
8.  Co-Inoculation with Rhizobia and AMF Inhibited Soybean Red Crown Rot: From Field Study to Plant Defense-Related Gene Expression Analysis 
PLoS ONE  2012;7(3):e33977.
Soybean red crown rot is a major soil-borne disease all over the world, which severely affects soybean production. Efficient and sustainable methods are strongly desired to control the soil-borne diseases.
Principal Findings
We firstly investigated the disease incidence and index of soybean red crown rot under different phosphorus (P) additions in field and found that the natural inoculation of rhizobia and arbuscular mycorrhizal fungi (AMF) could affect soybean red crown rot, particularly without P addition. Further studies in sand culture experiments showed that inoculation with rhizobia or AMF significantly decreased severity and incidence of soybean red crown rot, especially for co-inoculation with rhizobia and AMF at low P. The root colony forming unit (CFU) decreased over 50% when inoculated by rhizobia and/or AMF at low P. However, P addition only enhanced CFU when inoculated with AMF. Furthermore, root exudates of soybean inoculated with rhizobia and/or AMF significantly inhibited pathogen growth and reproduction. Quantitative RT-PCR results indicated that the transcripts of the most tested pathogen defense-related (PR) genes in roots were significantly increased by rhizobium and/or AMF inoculation. Among them, PR2, PR3, PR4 and PR10 reached the highest level with co-inoculation of rhizobium and AMF.
Our results indicated that inoculation with rhizobia and AMF could directly inhibit pathogen growth and reproduction, and activate the plant overall defense system through increasing PR gene expressions. Combined with optimal P fertilization, inoculation with rhizobia and AMF could be considered as an efficient method to control soybean red crown rot in acid soils.
PMCID: PMC3307780  PMID: 22442737
9.  Spironolactone Attenuates Experimental Uremic Cardiomyopathy by Antagonizing Marinobufagenin 
Hypertension  2009;54(6):1313-1320.
Spironolactone has been noted to attenuate cardiac fibrosis. We have observed that the cardiotonic steroid marinobufagenin plays an important role in the diastolic dysfunction and cardiac fibrosis seen with experimental renal failure. We performed the following studies to determine whether and how spironolactone might ameliorate these changes. First, we studied rats subjected to partial nephrectomy or administration of exogenous marinobufagenin. We found that spironolactone (20 mg/kg per day) attenuated the diastolic dysfunction as assessed by ventricular pressure-volume loops and essentially eliminated cardiac fibrosis as assessed by trichrome staining and Western blot. Next, we examined the effects of spironolactone and its major metabolite, canrenone (both 100 nM), on marinobufagenin stimulation of rat cardiac fibroblasts. Both spironolactone and canrenone prevented the stimulation of collagen production by 1 nM marinobufagenin but not 100 nM marinobufagenin, as assessed by proline incorporation and procollagen 1 expression, as well as signaling through the sodium-potassium-ATPase, as evidenced by protein kinase C isoform δ translocation and extracellular signal regulated kinase 1/2 activation. Both spironolactone and canrenone also altered ouabain binding to cultured porcine cells in a manner consistent with competitive inhibition. Our data suggest that some of the antifibrotic effects of spironolactone may be attributed to antagonism of marinobufagenin signaling through the sodium-potassium-ATPase.
PMCID: PMC2783263  PMID: 19884563
cardiomyopathy; renal failure; cardiotonic steroids; collagen; fibrosis
10.  Aluminium tolerance and high phosphorus efficiency helps Stylosanthes better adapt to low-P acid soils 
Annals of Botany  2009;103(8):1239-1247.
Backgrond and Aims
Stylosanthes spp. (stylo) is one of the most important pasture legumes used in a wide range of agricultural systems on acid soils, where aluminium (Al) toxicity and phosphorus (P) deficiency are two major limiting factors for plant growth. However, physiological mechanisms of stylo adaptation to acid soils are not understood.
Twelve stylo genotypes were surveyed under field conditions, followed by sand and nutrient solution culture experiments to investigate possible physiological mechanisms of stylo adaptation to low-P acid soils.
Key Results
Stylo genotypes varied substantially in growth and P uptake in low P conditions in the field. Three genotypes contrasting in P efficiency were selected for experiments in nutrient solution and sand culture to examine their Al tolerance and ability to utilize different P sources, including Ca-P, K-P, Al-P, Fe-P and phytate-P. Among the three tested genotypes, the P-efficient genotype ‘TPRC2001-1’ had higher Al tolerance than the P-inefficient genotype ‘Fine-stem’ as indicated by relative tap root length and haematoxylin staining. The three genotypes differed in their ability to utilize different P sources. The P-efficient genotype, ‘TPRC2001-1’, had superior ability to utilize phytate-P.
The findings suggest that possible physiological mechanisms of stylo adaptation to low-P acid soils might involve superior ability of plant roots to tolerate Al toxicity and to utilize organic P and Al-P.
PMCID: PMC2685318  PMID: 19324896
Stylosanthes; phosphorus; P efficiency; organic P; Al toxicity; acid soil
11.  Prenatal and Perinatal Risk Factors for Autism in China 
We conducted a case–control study using 190 Han children with and without autism to investigate prenatal and perinatal risk factors for autism in China. Cases were recruited through public special education schools and controls from regular public schools in the same region (Tianjin), with frequency matching on sex and birth year. Unadjusted analyses identified seven prenatal and seven perinatal risk factors significantly associated with autism. In the adjusted analysis, nine risk factors showed significant association with autism: maternal second-hand smoke exposure, maternal chronic or acute medical conditions unrelated to pregnancy, maternal unhappy emotional state, gestational complications, edema, abnormal gestational age (<35 or >42 weeks), nuchal cord, gravidity >1, and advanced paternal age at delivery (>30 year-old).
PMCID: PMC2974190  PMID: 20358271
Autism; China; Prenatal; Perinatal; Risk factors
12.  Partial nephrectomy as a model for uremic cardiomyopathy in the mouse 
Because of the plethora of genetic manipulations available in the mouse, we performed a partial nephrectomy in the mouse and examined whether the phenotypical features of uremic cardiomyopathy described in humans and rats were also present in the murine model. A ⅚ nephrectomy was performed using a combination of electrocautory to decrease renal mass on the left kidney and right surgical nephrectomy. This procedure produced substantial and persistent hypertension as well as increases in circulating concentrations of marinobufagenin. Invasive physiological measurements of cardiac function demonstrated that the ⅚ nephrectomy resulted in impairment of both active and passive left ventricular relaxation at 4 wk whereas tissue Doppler imaging detected changes in diastolic function after 6 wk. Morphologically, hearts demonstrated enlargement and progressive fibrosis, and biochemical measurements demonstrated downregulation of the sarcoplasmic reticulum calcium ATPase as well as increases in collagen-1, fibronectin, and vimentin expression. Our results suggest that partial nephrectomy in the mouse establishes a model of uremic cardiomyopathy which shares phenotypical features with the rat model as well as patients with chronic renal failure.
PMCID: PMC2742580  PMID: 18032546
renal failure; TGF-β; cardiotonic steroids; reactive oxygen species; fibrosis
13.  Molecular epidemiology of measles viruses in China, 1995–2003 
Virology Journal  2007;4:14.
This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%–100% and 93.3%–100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China.
PMCID: PMC1802751  PMID: 17280609
14.  Binding of Src to Na+/K+-ATPase Forms a Functional Signaling Complex 
Molecular Biology of the Cell  2006;17(1):317-326.
We have shown that ouabain activates Src, resulting in subsequent tyrosine phosphorylation of multiple effectors. Here, we tested if the Na+/K+-ATPase and Src can form a functional signaling complex. In LLC-PK1 cells the Na+/K+-ATPase and Src colocalized in the plasma membrane. Fluorescence resonance energy transfer analysis indicated that both proteins were in close proximity, suggesting a direct interaction. GST pulldown assay showed a direct, ouabain-regulated, and multifocal interaction between the α1 subunit of Na+/K+-ATPase and Src. Although the interaction between the Src kinase domain and the third cytosolic domain (CD3) of α1 is regulated by ouabain, the Src SH3SH2 domain binds to the second cytosolic domain constitutively. Functionally, binding of Src to either the Na+/K+-ATPase or GST-CD3 inhibited Src activity. Addition of ouabain, but not vanadate, to the purified Na+/K+-ATPase/Src complex freed the kinase domain and restored the Src activity. Consistently, exposure of intact cells to ouabain apparently increased the distance between the Na+/K+-ATPase and Src. Concomitantly, it also stimulated tyrosine phosphorylation of the proteins that are associated with the Na+/K+-ATPase. These new findings illustrate a novel molecular mechanism of signal transduction involving the interaction of a P-type ATPase and a nonreceptor tyrosine kinase.
PMCID: PMC1345669  PMID: 16267270
15.  Na/K-ATPase Tethers Phospholipase C and IP3 Receptor into a Calcium-regulatory Complex 
Molecular Biology of the Cell  2005;16(9):4034-4045.
We have shown that the caveolar Na/K-ATPase transmits ouabain signals via multiple signalplexes. To obtain the information on the composition of such complexes, we separated the Na/K-ATPase from the outer medulla of rat kidney into two different fractions by detergent treatment and density gradient centrifugation. Analysis of the light fraction indicated that both PLC-γ1 and IP3 receptors (isoforms 2 and 3, IP3R2 and IP3R3) were coenriched with the Na/K-ATPase, caveolin-1 and Src. GST pulldown assays revealed that the central loop of the Na/K-ATPase α1 subunit interacts with PLC-γ1, whereas the N-terminus binds IP3R2 and IP3R3, suggesting that the signaling Na/K-ATPase may tether PLC-γ1 and IP3 receptors together to form a Ca2+-regulatory complex. This notion is supported by the following findings. First, both PLC-γ1 and IP3R2 coimmunoprecipitated with the Na/K-ATPase and ouabain increased this interaction in a dose- and time-dependent manner in LLC-PK1 cells. Depletion of cholesterol abolished the effects of ouabain on this interaction. Second, ouabain induced phosphorylation of PLC-γ1 at Tyr783 and activated PLC-γ1 in a Src-dependent manner, resulting in increased hydrolysis of PIP2. It also stimulated Src-dependent tyrosine phosphorylation of the IP3R2. Finally, ouabain induced Ca2+ release from the intracellular stores via the activation of IP3 receptors in LLC-PK1 cells. This effect required the ouabain-induced activation of PLC-γ1. Inhibition of Src or depletion of cholesterol also abolished the effect of ouabain on intracellular Ca2+.
PMCID: PMC1196317  PMID: 15975899

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