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1.  Facile synthesis, microstructure and photophysical properties of core-shell nanostructured (SiCN)/BN nanocomposites 
Scientific Reports  2017;7:39866.
Increasing structural complexity at nanoscale can permit superior control over photophysical properties in the precursor-derived semiconductors. We demonstrate here the synthesis of silicon carbonitride (SiCN)/boron nitride (BN) nanocomposites via a polymer precursor route wherein the cobalt polyamine complexes used as the catalyst, exhibiting novel composite structures and photophysical properties. High Resolution Transmission Electron Microscopy (HRTEM) analysis shows that the diameters of SiCN−BN core−shell nanocomposites and BN shells are 50‒400 nm and 5‒25 nm, respectively. BN nanosheets (BNNSs) are also observed with an average sheet size of 5‒15 nm. The photophysical properties of these nanocomposites are characterized using the UV-Vis and photoluminescence (PL) analyses. The as-produced composites have emission behavior including an emission lifetime of 2.5 ns (±20 ps) longer observed in BN doped SiCN than that seen for SiC nanoparticles. Our results suggest that the SiCN/BN nanocomposites act as semiconductor displaying superior width photoluminescence at wavelengths spanning the visible to near-infrared (NIR) spectral range (400‒700 nm), owing to the heterojunction of the interface between the SiC(N) nanowire core and the BN nanosheet shell.
PMCID: PMC5233973  PMID: 28084300
2.  Transcript profile analysis reveals important roles of jasmonic acid signalling pathway in the response of sweet potato to salt stress 
Scientific Reports  2017;7:40819.
Sweet potato is an important food and bio-energy crop, and investigating the mechanisms underlying salt tolerance will provide information for salt-tolerant breeding of this crop. Here, the root transcriptomes of the salt-sensitive variety Lizixiang and the salt-tolerant line ND98 were compared to identify the genes and pathways involved in salt stress responses. In total, 8,744 and 10,413 differentially expressed genes (DEGs) in Lizixiang and ND98, respectively, were involved in salt responses. A lower DNA methylation level was detected in ND98 than in Lizixiang. In both genotypes, the DEGs, which function in phytohormone synthesis and signalling and ion homeostasis, may underlie the different degrees of salt tolerance. Significant up-regulations of the genes involved in the jasmonic acid (JA) biosynthesis and signalling pathways and ion transport, more accumulation of JA, a higher degree of stomatal closure and a lower level of Na+ were found in ND98 compared to Lizixiang. This is the first report on transcriptome responses to salt tolerance in sweet potato. These results reveal that the JA signalling pathway plays important roles in the response of sweet potato to salt stress. This study provides insights into the mechanisms and genes involved in the salt tolerance of sweet potato.
PMCID: PMC5234020  PMID: 28084460
3.  Negative immune factors might predominate local tumor immune status and promote carcinogenesis in cervical carcinoma 
Virology Journal  2017;14:5.
The disequilibrium of local immune microenvironment is an essential element during tumorigenesis.
By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix.
The FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection.
Our data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.
Trial registration
Not applicable.
PMCID: PMC5237320  PMID: 28086903
Cervical cancer; Immune microenvironment; Immune factors
4.  Oriented and Ordered Biomimetic Remineralization of the Surface of Demineralized Dental Enamel Using HAP@ACP Nanoparticles Guided by Glycine 
Scientific Reports  2017;7:40701.
Achieving oriented and ordered remineralization on the surface of demineralized dental enamel, thereby restoring the satisfactory mechanical properties approaching those of sound enamel, is still a challenge for dentists. To mimic the natural biomineralization approach for enamel remineralization, the biological process of enamel development proteins, such as amelogenin, was simulated in this study. In this work, carboxymethyl chitosan (CMC) conjugated with alendronate (ALN) was applied to stabilize amorphous calcium phosphate (ACP) to form CMC/ACP nanoparticles. Sodium hypochlorite (NaClO) functioned as the protease which decompose amelogenin in vivo to degrade the CMC-ALN matrix and generate HAP@ACP core-shell nanoparticles. Finally, when guided by 10 mM glycine (Gly), HAP@ACP nanoparticles can arrange orderly and subsequently transform from an amorphous phase to well-ordered rod-like apatite crystals to achieve oriented and ordered biomimetic remineralization on acid-etched enamel surfaces. This biomimetic remineralization process is achieved through the oriented attachment (OA) of nanoparticles based on non-classical crystallization theory. These results indicate that finding and developing analogues of natural proteins such as amelogenin involved in the biomineralization by natural macromolecular polymers and imitating the process of biomineralization would be an effective strategy for enamel remineralization. Furthermore, this method represents a promising method for the management of early caries in minimal invasive dentistry (MID).
PMCID: PMC5228061  PMID: 28079165
5.  Bromodomain protein Brd3 promotes Ifnb1 transcription via enhancing IRF3/p300 complex formation and recruitment to Ifnb1 promoter in macrophages 
Scientific Reports  2017;7:39986.
As members of bromodomain and extra-terminal motif protein family, bromodomain-containing proteins regulate a wide range of biological processes including protein scaffolding, mitosis, cell cycle progression and transcriptional regulation. The function of these bromodomain proteins (Brds) in innate immune response has been reported but the role of Brd3 remains unclear. Here we find that virus infection significantly downregulate Brd3 expression in macrophages and Brd3 knockout inhibits virus-triggered IFN-β production. Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection. Importantly, Brd3 promotes the recruitment of IRF3/p300 complex to the promoter of Ifnb1, and increases the acetylation of histone3/histone4 within the Ifnb1 promoter, leading to the enhancement of type I interferon production. Therefore, our work indicated that Brd3 may act as a coactivator in IRF3/p300 transcriptional activation of Ifnb1 and provided new epigenetic mechanistic insight into the efficient activation of the innate immune response.
PMCID: PMC5206742  PMID: 28045112
6.  Brain Volume as an Integrated Marker for the Risk of Death in a Community-Based Sample: Age Gene/Environment Susceptibility—Reykjavik Study 
Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort.
The analysis includes 3,543 men and women (born 1907–1935) participating in the Age, Gene, Environment Susceptibility—Reykjavik Study. Participants with a known brain-related high risk for mortality (cognitive impairment or stroke) were excluded from these analyses. Quantitative estimates of total brain volume, white matter, white matter lesions, total gray matter (GM; cortical GM and subcortical GM separately), and focal cerebral vascular disease were generated from brain magnetic resonance imaging. Brain atrophy was expressed as brain tissue volume divided by total intracranial volume, yielding a percentage. Mean follow-up duration was 7.2 (0–10) years, with 647 deaths. Cox regression was used to analyze the association of mortality to brain atrophy, adjusting for demographics, cardiovascular risk factors, and cerebral vascular disease.
Reduced risk of mortality was significantly associated with higher total brain volume (hazard ratio, 95% confidence interval = 0.71, 0.65–0.78), white matter (0.85, 0.78–0.93), total GM (0.74, 0.68–0.81), and cortical GM (0.78, 0.70-0.87). Overall, the associations were similar for cardiovascular and noncardiovascular-related deaths.
Independent of multiple risk factors and cerebral vascular damage, global brain volume predicts mortality in a large nondemented stroke-free community-dwelling older cohort. Total brain volume may be an integrated measure reflecting a range of health and with further investigation could be a useful clinical tool when assessing risk for mortality.
PMCID: PMC4706101  PMID: 25359930
Brain aging; Epidemiology; Neuroimaging ; Mortality risking.
7.  Neddylation requires glycyl-tRNA synthetase to protect activated E2 
Neddylation is a post-translational modification that controls cell cycle and proliferation by conjugating the ubiquitin-like protein NEDD8 to specific targets. Here we report that glycyl-tRNA synthetase (GlyRS), an essential enzyme for protein synthesis, also plays a critical role in neddylation. In human cells, knockdown of GlyRS, but not a different tRNA synthetase, decreases the global level of neddylation and causes cell cycle abnormality. This function of GlyRS is achieved through direct interactions with multiple components of the neddylation pathway, including NEDD8, E1, and E2 (Ubc12). Using various structural and functional approaches, we show that GlyRS binds to the APPBP1 subunit of E1 to capture and protect the activated E2 (NEDD8-conjugated Ubc12) before it reaches a downstream target. Therefore, GlyRS functions as a chaperone to critically support neddylation. This function is likely to be conserved in all eukaryotic GlyRS, and may contribute to the strong association of GlyRS with cancer progression.
PMCID: PMC4972647  PMID: 27348078
8.  Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response 
Journal of Virology  2016;90(14):6573-6582.
Bats harbor severe acute respiratory syndrome (SARS)-like coronaviruses (SL-CoVs) from which the causative agent of the 2002-2003 SARS pandemic is thought to have originated. However, despite the fact that a large number of genetically diverse SL-CoV sequences have been detected in bats, only two strains (named WIV1 and WIV16) have been successfully cultured in vitro. These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1 (rWIV1), an ORFX deletion mutant (rWIV1-ΔX), and a green fluorescent protein (GFP)-expressing mutant (rWIV1-GFP-ΔX). Northern blotting and fluorescence microscopy indicate that ORFX was expressed during WIV1 infection. A virus infection assay showed that rWIV1-ΔX replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells. Further study showed that ORFX could inhibit interferon production and activate NF-κB. Our results demonstrate for the first time that the unique ORFX in the WIV1 strain is a functional gene involving modulation of the host immune response but is not essential for in vitro viral replication.
IMPORTANCE Bats harbor genetically diverse SARS-like coronaviruses (SL-CoVs), and some of them have the potential for interspecies transmission. A unique open reading frame (ORFX) was identified in the genomes of two recently isolated bat SL-CoV strains (WIV1 and -16). It will therefore be critical to clarify whether and how this protein contributes to virulence during viral infection. Here we revealed that the unique ORFX is a functional gene that is involved in the modulation of the host immune response but is not essential for in vitro viral replication. Our results provide important information for further exploration of the ORFX function in the future. Moreover, the reverse genetics system we constructed will be helpful for study of the pathogenesis of this group of viruses and to develop therapeutics for future control of emerging SARS-like infections.
PMCID: PMC4936131  PMID: 27170748
9.  Plasmodium falciparum malaria importation from Africa to China and its mortality: an analysis of driving factors 
Scientific Reports  2016;6:39524.
Plasmodium falciparum malaria importation from Africa to China is rising with increasing Chinese overseas investment and international travel. Identifying networks and drivers of this phenomenon as well as the contributors to high case-fatality rate is a growing public health concern to enable efficient response. From 2011–2015, 8653 P. falciparum cases leading to 98 deaths (11.3 per 1000 cases) were imported from 41 sub-Saharan countries into China, with most cases (91.3%) occurring in labour-related Chinese travellers. Four strongly connected groupings of origin African countries with destination Chinese provinces were identified, and the number of imported cases was significantly associated with the volume of air passengers to China (P = 0.006), parasite prevalence in Africa (P < 0.001), and the amount of official development assistance from China (P < 0.001) with investment in resource extraction having the strongest relationship with parasite importation. Risk factors for deaths from imported cases were related to the capacity of malaria diagnosis and diverse socioeconomic factors. The spatial heterogeneity uncovered, principal drivers explored, and risk factors for mortality found in the rising rates of P. falciparum malaria importation to China can serve to refine malaria elimination strategies and the management of cases, and high risk groups and regions should be targeted.
PMCID: PMC5175130  PMID: 28000753
10.  The effect of Chinese herbs and its effective components on coronary heart disease through PPARs-PGC1α pathway 
DanQi pill (DQP) is prescribed widely in China and has definite cardioprotective effect on coronary heart disease. Our previous studies proved that DQP could effectively regulate plasma levels of high density lipoprotein (HDL) and low density lipoprotein (LDL). However, the regulatory mechanisms of DQP and its major components Salvianolic acids and Panax notoginseng saponins (DS) on lipid metabolism disorders haven’t been comprehensively studied so far.
Rat model of coronary heart disease was induced by left anterior descending (LAD) artery ligation operations. Rats were divided into sham, model, DQP treated, DS treated and positive drug (clofibrate) treated groups. At 28 days after surgery, cardiac functions were assessed by echocardiography. Expressions of transcription factors and key molecules in energy metabolism pathway were measured by reverse transcriptase polymerase chain reaction or western blotting.
In ischemic heart model, cardiac functions were severely injured but improved by treatments of DQP and DS. Expression of LPL was down-regulated in model group. Both DQP and DS could up-regulate the mRNA expression of LPL. Membrane proteins involved in lipid transport and uptake, such as FABP4 and CPT-1A, were down-regulated in ischemic heart tissues. Treatment with DQP and DS regulated lipid metabolisms by up-regulating expressions of FABP4 and CPT-1A. DQP and DS also suppressed expression of cytochrome P450. Furthermore, transcriptional factors, such as PPARα, PPARγ, RXRA and PGC-1α, were down-regulated in ischemic model group. DQP and DS could up-regulate expressions of these factors. However, DS showed a better efficacy than DQP on PGC-1α, a coactivator of PPARs. Key molecules in signaling pathways such as AKT1/2, ERK and PI3K were also regulated by DQP and DS simultaneously.
Salvianolic acids and Panax notoginseng are the major effective components of DanQi pill in improving lipid metabolism in ischemic heart model. The effects may be mediated by regulating transcriptional factors such as PPARs, RXRA and PGC-1α.
PMCID: PMC5153825  PMID: 27955667
Components; Coronary heart disease; PPARs-PGC1α pathway; DanQi pill
11.  Biological Databases for Hematology Research 
With the advances of genome-wide sequencing technologies and bioinformatics approaches, a large number of datasets of normal and malignant erythropoiesis have been generated and made public to researchers around the world. Collection and integration of these datasets greatly facilitate basic research and clinical diagnosis and treatment of blood disorders. Here we provide a brief introduction of the most popular omics data resources of normal and malignant hematopoiesis, including some integrated web tools, to help users get better equipped to perform common analyses. We hope this review will promote the awareness and facilitate the usage of public database resources in the hematology research.
PMCID: PMC5200935  PMID: 27965103
Hematology; Hematological diseases; Omics data resources; Database; Bioinformatics
12.  Predicting Early Death Among Elderly Dialysis Patients: Development and Validation of a Risk Score to Assist Shared Decision Making for Dialysis Initiation 
A shared decision-making tool could help elderly advanced chronic kidney disease (CKD) patients decide about initiating dialysis. Since mortality may be high in the first few months after initiating dialysis, incorporating early mortality predictors in such a tool would be important for an informed decision. Our objective is to derive and validate a predictive risk score for early mortality after initiating dialysis.
Study Design
Retrospective observational cohort, with development and validation cohorts.
Setting & Participants
US Renal Data System (USRDS) and claims data from the Centers for Medicare & Medicaid Services for 69,441 (aged ≥67 years) end-stage renal disease (ESRD) patients with previous 2-year Medicare history who initiated dialysis January 1, 2009–December 31, 2010.
Candidate Predictors
Demographics, predialysis care, laboratory data, functional limitations and medical history.
All-cause mortality in the first 3 and 6 months.
Analytical Approach
Predicted mortality via logistic regression.
The simple risk score (total score, 0–9) included age (0–3 points); low albumin, assistance with daily living, nursing home residence, cancer, heart failure, and hospitalization (1 point each), and showed area under the receiver operating characteristic curve (AUROC) =0.69 in the validation sample. A comprehensive risk score with additional predictors was also developed (with AUROC=0.72, high concordance between predicted vs. observed risk). Mortality probabilities were estimated from these models: the median score of 3 indicating 12% risk in 3 months and 20% in 6 months, and the highest scores (≥8) indicating 39% risk in 3 months and 55% in 6 months.
Patients who did not choose dialysis and who did not have 2 year Medicare history were excluded.
Routinely available information can be used by CKD patients, families and their nephrologists to estimate risk of early mortality after dialysis initiation, which may facilitate informed decision-making regarding treatment options.
PMCID: PMC4658211  PMID: 26123861
end-stage renal disease (ESRD); chronic kidney failure; dialysis initation; conservative care; predictive model; mortality; dialysis initiation; risk score; shared decision-making; treatment decisions; quality of life; Choosing Wisely
13.  Qishen granules inhibit myocardial inflammation injury through regulating arachidonic acid metabolism 
Scientific Reports  2016;6:36949.
Qishen granules (QSG), a traditional Chinese medicine, have been prescribed widely in the treatment of coronary heart diseases. Previous studies demonstrated that QSG had anti-inflammatory and cardio-protective effects in mice with acute myocardial infarction (AMI). However, the mechanisms by which QSG attenuate inflammation and prevent post-AMI heart failure (HF) are still unclear. In this study, we explored the anti-inflammatory mechanisms of QSG by in vitro and in vivo experiments. A novel inflammatory injury model of H9C2 cells was induced by lipopolysaccharide (LPS)-stimulated macrophage-conditioned media (CM). An animal model of AMI was conducted by ligation of left anterior descending (LAD) coronary artery in mice. We found that QSG inhibited release of cytokines from LPS-stimulated RAW 264.7 macrophages and protected H9C2 cardiac cells against CM-induced injury. In vivo results showed that QSG administration could improve cardiac functions and alter pathological changes in model of AMI. QSG regulated multiple key molecules, including phospholipases A2 (PLA2), cyclooxygenases (COXs) and lipoxygenases (LOXs), in arachidonic acid metabolism pathway. Interestingly, QSG also targeted TNF-α-NF-κB and IL-6-JAK2-STAT3 signaling pathways. Taken together, QSG achieve synergistic effects in mitigating post-AMI HF by regulating multiple targets in inflammatory pathways. This study provides insights into anti-inflammatory therapeutics in managing HF after AMI.
PMCID: PMC5105076  PMID: 27833128
14.  Genome-Wide Identification and Analysis of MicroRNAs Involved in Witches’-Broom Phytoplasma Response in Ziziphus jujuba 
PLoS ONE  2016;11(11):e0166099.
MicroRNAs (miRNAs) play an important role in responding to biotic and abiotic stresses in plants. Jujube witches’-broom a phytoplasma disease of Ziziphus jujuba is prevalent in China and is a serious problem to the industry. However, the molecular mechanism of the disease is poorly understood. In this study, genome-wide identification and analysis of microRNAs in response to witches’-broom was performed. A total of 85 conserved miRNA unique sequences belonging to 32 miRNA families and 24 novel miRNA unique sequences, including their complementary miRNA* strands were identified from small RNA libraries derived from a uninfected and witches’-broom infected Z. jujuba plant. Differentially expressed miRNAs associated with Jujube witches’-broom disease were investigated between the two libraries, and 12 up-regulated miRNAs and 10 down- regulated miRNAs identified with more than 2 fold changes. Additionally, 40 target genes of 85 conserved miRNAs and 49 target genes of 24 novel miRNAs were predicted and their putative functions assigned. Using the modified 5’-RACE method, we confirmed that SPL and MYB were cleaved by miR156 and miR159, respectively. Our results provide insight into the molecular mechanisms of witches’-broom disease in Z. jujuba.
PMCID: PMC5100886  PMID: 27824938
15.  Risk assessment of malaria in land border regions of China in the context of malaria elimination 
Malaria Journal  2016;15:546.
Cross-border malaria transmission poses a challenge for countries to achieve and maintain malaria elimination. Because of a dramatic increase of cross-border population movement between China and 14 neighbouring countries, the malaria epidemic risk in China’s land border regions needs to be understood.
In this study, individual case-based epidemiological data on malaria in the 136 counties of China with international land borders, from 2011 to 2014, were extracted from the National Infectious Disease Information System. The Plasmodium species, seasonality, spatiotemporal distribution and changing features of imported and indigenous cases were analysed using descriptive spatial and temporal methods.
A total of 1948 malaria cases were reported, with 1406 (72.2%) imported cases and 542 (27.8%) indigenous cases. Plasmodium vivax is the predominant species, with 1536 malaria cases occurrence (78.9%), following by Plasmodium falciparum (361 cases, 18.5%), and the others (51 cases, 2.6%). The magnitude and geographic distribution of malaria in land border counties shrunk sharply during the elimination period. Imported malaria cases were with a peak of 546 cases in 2011, decreasing yearly in the following years. The number of counties with imported cases decreased from 28 counties in 2011 to 26 counties in 2014. Indigenous malaria cases presented a markedly decreasing trend, with 319 indigenous cases in 2011 reducing to only 33 indigenous cases in 2014. The number of counties with indigenous cases reduced from 26 counties in 2011 to 10 counties in 2014. However, several bordering counties of Yunnan province adjacent to Myanmar reported indigenous malaria cases in the four consecutive years from 2011 to 2014.
The scale and extent of malaria occurrence in the international land border counties of China decreased dramatically during the elimination period. However, several high-risk counties, especially along the China–Myanmar border, still face a persistent risk of malaria introduction and transmission. The study emphasizes the importance and urgency of cross-border cooperation between neighbouring countries to jointly face malaria threats to elimination goals.
PMCID: PMC5101710  PMID: 27825379
Malaria; Border; Epidemiology; Elimination; China
16.  Estimating long-term clinical effectiveness and cost-effectiveness of HPV 16/18 vaccine in China 
BMC Cancer  2016;16:848.
Human papillomavirus (HPV) 16 and 18 are the two most common HPV oncogenic types that can be prevented by vaccination. This study aimed at assessing the cost-effectiveness of 3 doses of the bivalent HPV vaccine in rural and urban settings in China.
A Markov model was adapted to reflect the lifetime of a modelled 100,000 12-year-old girls cohort in rural and urban settings in China. Input parameters were obtained from published literature, official reports and a two-round expert review panel. Clinical and economic outcomes of vaccination at age 12 with screening was compared to screening only. In the base case analysis, a 3 % discount rate, the vaccine cost of 247 CNY (US$ 39, PAHO vaccine cost in 2013), two rounds of screening in a life time and 70 % coverage for both screening and vaccination were used. One-way, two-way and probabilistic sensitivity analyses were performed. We used different thresholds of cost-effectiveness to reflect the diversity of economic development in China.
Vaccination in addition to screening could prevent 60 % more cervical cancer cases and deaths than screening only. The incremental cost effectiveness ratio varied largely when changing cost of vaccination and discount in one way analysis. Vaccination was very cost-effective when the vaccine cost ranged 87-630 CNY (US$ 13.8-100) in rural and 87-750 CNY (US$ 13.8–119) in urban; and remained cost-effective when the vaccine cost ranged 630–1,700 CNY (US$ 100–270) in rural and 750–1,900 CNY (US$ 119–302) in urban in two way analysis. Probabilistic sensitivity analyses showed that model results were robust.
In both rural and urban, the vaccination cost and discounting are important factors determining the cost-effectiveness of HPV vaccination; policy makers in China should take these into account when making a decision on the introduction of HPV vaccine. In areas with a high burden of cervical cancer and limited screening activities, HPV vaccination should be prioritized. However, the vaccine cost needs to be reduced in order to make it very cost-effective and affordable as well, in particular in poverty areas with high disease burden.
Electronic supplementary material
The online version of this article (doi:10.1186/s12885-016-2893-x) contains supplementary material, which is available to authorized users.
PMCID: PMC5097411  PMID: 27814703
Cervical cancer; HPV vaccine; Cost-effectiveness
17.  Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population 
Scientific Reports  2016;6:35171.
Recent studies have linked certain single nucleotide polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) gene with Parkinson’s disease (PD). The R1628P variant of LRRK2 may be a specific risk factor for PD in ethnic Han-Chinese populations. This study is to elucidate the epidemiological feature of R1628P in ethnic Han-Chinese population with PD. A comprehensive meta-analysis was performed to evaluate the precise association between R1628P variant and the risk for PD in ethnic Han-Chinese and subgroups stratified by gender, onset age, or family history. The analysis assessing the role of R1628P on the risk of PD in ethnic Han-Chinese supported a significant association, and the odds ratio was 1.86. We further estimate the specific prevalence in relevant ethnic Han-Chinese subgroups. After stratifying the eligible data by gender, onset age, or family history, significant associations were found in all male, female, early-onset, late-onset, familial and sporadic subgroups, and the odds ratio were 1.90, 1.94, 2.12, 1.75, 6.71 and 1.81 respectively. In conclusion, our meta-analysis suggests that R1628P variant of LRRK2 has a significant association with the risk of PD in ethnic Han-Chinese and subgroup population.
PMCID: PMC5095708  PMID: 27812003
18.  Alterations in soil microbial community composition and biomass following agricultural land use change 
Scientific Reports  2016;6:36587.
The effect of agricultural land use change on soil microbial community composition and biomass remains a widely debated topic. Here, we investigated soil microbial community composition and biomass [e.g., bacteria (B), fungi (F), Arbuscular mycorrhizal fungi (AMF) and Actinomycete (ACT)] using phospholipid fatty acids (PLFAs) analysis, and basal microbial respiration in afforested, cropland and adjacent uncultivated soils in central China. We also investigated soil organic carbon and nitrogen (SOC and SON), labile carbon and nitrogen (LC and LN), recalcitrant carbon and nitrogen (RC and RN), pH, moisture, and temperature. Afforestation averaged higher microbial PLFA biomass compared with cropland and uncultivated soils with higher values in top soils than deep soils. The microbial PLFA biomass was strongly correlated with SON and LC. Higher SOC, SON, LC, LN, moisture and lower pH in afforested soils could be explained approximately 87.3% of total variation of higher total PLFAs. Afforestation also enhanced the F: B ratios compared with cropland. The basal microbial respiration was higher while the basal microbial respiration on a per-unit-PLFA basis was lower in afforested land than adjacent cropland and uncultivated land, suggesting afforestation may increase soil C utilization efficiency and decrease respiration loss in afforested soils.
PMCID: PMC5095713  PMID: 27812029
19.  Removal of foreign bodies embedded in the urinary bladder wall by a combination of laparoscopy and carbon dioxide cystoscopic assistance: Case report and literature review 
To report a case of combined laparoscopic and carbon dioxide partial cystectomy and foreign body removal and to review the existing literature on the topic.
Materials and Methods
A 43-year-old Asian woman was found to have an intrauterine device embedded in the bladder wall during evaluation for chronic pelvic pain and urinary tract infection. She underwent cystoscopic-laparoscopic partial cystectomy, with an uncomplicated postoperative course. She had normal renal function during the follow-up period. This case demonstrates the possibility and safety of performing cystoscopic-laparoscopic partial cystectomy for the removal of a partially implanted intravesical foreign body.
The patient recovered without incident and was discharged 7 days after surgery. No abnormalities were noted in the urine output or renal function in the postoperative follow-up period. No complications due to retrograde flow of carbon dioxide up the ureters or air embolism were noted during the procedure or postoperatively.
The combination of laparoscopy and air cystoscopy has been shown to be an optimal method for retracting foreign bodies embedded in the bladder wall. Also, air cystoscopy can be used to give doctors a better view in cases in which vision is compromised under water-contrast cystoscopy.
PMCID: PMC5109789  PMID: 27847920
Cystoscopy; Intrauterine devices; Laparoscopy; Urinary bladder calculi
20.  The Association between Endometriosis, Tubal Ligation, Hysterectomy and Epithelial Ovarian Cancer: Meta-Analyses 
To investigate the association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer. Relevant published literatures were searched in PubMed, ProQuest, Web of Science and Medline databases during 1995–2016. Heterogeneity was evaluated by I2 statistic. Publication bias was tested by funnel plot and Egger’s test. Odds ratio and 95% CI were used to assess the association strength. The statistical analyses in this study were accomplished by STATA software package. A total of 40,609 cases of epithelial ovarian cancer and 368,452 controls in 38 publications were included. The result suggested that endometriosis was associated with an increased risk of epithelial ovarian cancer (OR = 1.42, 95% CI = 1.28–1.57), tubal ligation was associated with a decreased risk of epithelial ovarian cancer (OR = 0.70, 95% CI = 0.60–0.81), while hysterectomy show no relationship with epithelial ovarian cancer (OR = 0.97, 95% CI = 0.81–1.14). A stratified analysis showed there were associations between endometriosis and the increased risk of epithelial ovarian cancer for studies conducted in USA and Europe. Meanwhile, there were associations between tubal ligation and the decreased risk of epithelial ovarian cancer for studies conducted in USA, Asia, Europe and Australia. The result indicated that endometriosis was a risk factor of epithelial ovarian cancer whereas tubal ligation was a protective risk factor of epithelial ovarian cancer, hysterectomy may have no relationship with epithelial ovarian cancer.
PMCID: PMC5129348  PMID: 27854255
epithelial ovarian cancer; endometriosis; hysterectomy; tubal ligation; meta-analysis
21.  Early Life Fructose Exposure and Its Implications for Long-Term Cardiometabolic Health in Offspring 
Nutrients  2016;8(11):685.
It has become increasingly clear that maternal nutrition can strongly influence the susceptibility of adult offspring to cardiometabolic disease. For decades, it has been thought that excessive intake of fructose, such as sugar-sweetened beverages and foods, has been linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. These deleterious effects of excess fructose consumption in adults are well researched, but limited data are available on the long-term effects of high fructose exposure during gestation, lactation, and infancy. This review aims to examine the evidence linking early life fructose exposure during critical periods of development and its implications for long-term cardiometabolic health in offspring.
PMCID: PMC5133073  PMID: 27809266
early life; fructose; sugar-sweetened beverages; cardiometabolic health; offspring
22.  Positive Regulation of Decidualization by l-Type Amino Acid Transporter 1 (lat1) in Pregnant Mice 
Nutrients  2016;8(11):704.
Amino acids have an important role in the pre and post implantation of placenta and embryo development. l-type amino-acid transporter 1 (lat1) is responsible for the transportation of large neutral amino acids and is mainly expressed in human fetal liver, placenta, brain, etc. This study is the first to investigate the expression of lat1 in the early pregnancy of mouse uteri and its role in the process of decidualization. Endometrial stromal cells of a mouse model were used to evaluate decidualization from Day 4–8 of pregnancy in vitro followed by lat1 knock down by small interfering RNA and by a competitive inhibitor of Leucine transport 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The effects of lat1 on decidualization in vivo were assessed by injecting BCH into the uterine horns. The mRNA and protein expressions of lat1 in the implantation sites were higher than that in the inter-implantation sites and were localized in the luminal and gland epithelium, stromal and decidual cells. Its increased expression (p < 0.05) was associated with artificial decidualization as well as activation of prl expression. Down-regulation of lat1 expression in these cells by siRNA and BCH inhibited the decidual progression in vitro. Inhibition of lat1 transportation by BCH controlled decidual progression in vivo also accompanied the down-regulation of prl, lat1 expression in the decidual area and embryo size on Day 8 of pregnancy. In conclusion, these results revealed that lat1 might play an important role in the decidual progression both in vitro and in vivo.
PMCID: PMC5133091  PMID: 27827961
decidualization; l-amino acid transporter-1 (lat1); stromal cell; pregnant mice
23.  Morphological and molecular characterisation of Myxobolus pronini n. sp. (Myxozoa: Myxobolidae) from the abdominal cavity and visceral serous membranes of the gibel carp Carassius auratus gibelio (Bloch) in Russia and China 
Parasites & Vectors  2016;9:562.
Myxozoa is a well-known economically and ecologically important group of metazoan parasites, phylogenetically related to Cnidaria. High diversity of myxosporeans has been recorded in Russia and China; however, most of the species were solely morphologically characterised. Here, we identified a new gibel carp-infecting Myxobolus species and morphologically and molecularly compared the Russian and Chinese isolates of this new myxosporean.
Myxobolus pronini n. sp. was found free in the abdominal cavity of Carassius auratus gibelio (Bloch, 1782) in Lake Baikal watershed, Russia, and embedded in the visceral serous membranes of the same fish species in Lake Taibai, Hubei province, China. The morphometric data of the plasmodia and mature spores exhibited some differences between the Russian and Chinese isolates, but SSU rDNA sequences indicated that these two geographical isolates are conspecific. The mature spores from the two locations are obovate in frontal view, with wider anterior than posterior end and lemon-shaped in sutural view. Spores of the Russian isolate were 14.3–16.2 (mean 15.1 ± 0.2) μm long, 9.6–10.8 (10.1 ± 0.1) μm wide and 6.4–7.4 (6.7 ± 0.15) μm thick; those of the Chinese isolate were 13.8–15.6 (14.7 ± 0.24) μm long, 9.6–13.3 (9.6 ± 0.65) μm wide and 6.2–7.2 (6.6 ± 0.16) μm thick. The newly-generated rDNA sequences (including SSU rDNA, ITS and LSU rDNA) from the two isolates represented some variations within the intraspecific range. Homology search by BLAST showed that the newly obtained rDNA sequences do not match any sequences available on GenBank. Phylogenetic analysis based on the aligned partial SSU rDNA sequences indicated that this novel species clustered with several gibel carp-infecting Myxobolus spp. with round anterior end of spores. Additionally, phylogenetic analysis based on all obtained ITS sequences showed that distinct genetic geographical differentiation occurred for this new parasite.
Myxobolus pronini n. sp. is described by integrating morphological, ecological and molecular evidence. Two geographical isolates of this species showed some morphological and genetic differences but within the intraspecific range of variation.
PMCID: PMC5080772  PMID: 27782848
Myxobolus pronini n. sp; Abdominal cavity; Serous membranes; Geographical variation; Gibel carp; Carassius auratus gibelio; Russia; China
24.  Role of Ring Finger Protein 213 in Moyamoya Disease 
Chinese Medical Journal  2016;129(20):2497-2501.
The aim of this study was to help people comprehensively understand the research advances related to ring finger protein 213 (RNF213) in moyamoya disease (MMD) and to understand the disease at the molecular level to provide a new perspective of the diagnosis of the disease.
Data Sources:
This review was based on data in articles published between 2005 and 2015 that were retrieved from the PubMed database. The search terms included RNF213, MMD, intracranial major artery stenosis/occlusion (ICASO), genotype, phenotype, mutant and variants, and the combinations of these terms.
Study Selection:
Articles related to MMD and RNF213 were selected for review, and we also reviewed publications related to ICASO.
RNF213 is not only associated with MMD but also associated with intracranial major artery stenosis. In addition, RNF213 variants exhibit apparent ethnic diversity; specifically, the c.14576G>A variant is mainly detected in Korean, Chinese, and Japanese populations, particularly the latter population. The genotypes of RNF213 correlate with the phenotypes of MMD; for example, the homozygous c.14576G>A variant is associated with early-onset, severe symptoms, and an unfavorable prognosis. Furthermore, the RNF213 c.14576G>A variant should be considered during the diagnosis of MMD because no patients with quasi-MMD have been reported to carry the RNF213 c.14576G>A variant whereas 66 of 78 patients with definite MMD have been found to carry this variant.
The growing literature demonstrates that MMD is primarily caused by the synergy of genetic and environmental factors, and unknown genetic modifiers might play roles in the etiology of MMD. Further research should be conducted to clarify the pathogenic mechanism of MMD.
PMCID: PMC5072264  PMID: 27748344
Moyamoya Disease; Research Progress; Ring Finger Protein 213; Variant
25.  Subcellular Evidence for Biogenesis of Autophagosomal Membrane during Spermiogenesis In vivo 
Although autophagosome formation has attracted substantial attention, the origin and the source of the autophagosomal membrane remains unresolved. The present study was designed to investigate in vivo subcellular evidence for the biogenesis of autophagosomal membrane during spermiogenesis using transmission-electron microscopy (TEM), Western blots and immunohistochemistry in samples from the Chinese soft-shelled turtle. The testis expressed LC3-II protein, which was located within spermatids at different stages of differentiation and indicated active autophagy. TEM showed that numerous autophagosomes were developed inside spermatids. Many endoplasmic reticulum (ER) were transferred into a special “Chrysanthemum flower center” (CFC) in which several double-layer isolation membranes (IM) were formed and extended. The elongated IM always engulfed some cytoplasm and various structures. Narrow tubules connected the ends of multiple ER and the CFC. The CFC was more developed in spermatids with compact nuclei than in spermatids with granular nuclei. An IM could also be transformed from a single ER. Sometimes an IM extended from a trans-Golgi network and wrapped different structures. The plasma membrane of the spermatid invaginated to form vesicles that were distributed among various endosomes around the CFC during spermiogenesis. All this cellular evidence suggests that, in vivo, IM was developed mainly by CFC produced from ER within differentiating spermatids during spermiogenesis. Vesicles from Golgi complexes, plasma membranes and endosomes might also be the sources of the autophagosome membrane.
PMCID: PMC5067523  PMID: 27803675
isolation membrane; “Chrysanthemum flower center”; endoplasmic reticulum; spermiogenesis; Chinese soft-shelled turtle

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