To describe the financial burden on TB patients for transportation during treatment, and to evaluate the impacts of the “transportation subsidy initiative on poor TB patients” in rural China for improving poor patients’ access to TB treatment.
A Case-cohort of 429 TB patients was investigated through questionnaire interviews in four counties of two provinces in China. Information on the financial burden for transportation during TB diagnosis and treatment was collected. Qualitative in-depth interviews with 26 TB patients were carried out to understand their perceptions of transportation subsidy initiative.
The mean transportation cost of TB medical care was 97 CNY (70 CNY in median), varying from 0 to 700 CNY. About 51% of the patients spent more than 10 CNY per round trip to the TB dispensary. Of the 429 TB patients investigated, 139 had received transportation subsidies after getting TB diagnosis; 15/139 (10.9%) showed dissatisfaction, mainly because the subsidy amount being insufficient. The income of patients receiving transportation subsidies was significantly lower than those not receiving the subsidies (p<0.05). The impression that an appropriate transportation subsidy enables patients to complete the required visits during their TB treatment was obtained after observation of over 80% of the patients.
The transportation subsidy plays an important role in reducing financial burden on poor TB patients for the completion of treatment. However, the coverage was limited and the amount of subsidy was not enough under the present policy. Considering the poverty of rural TB patients, a universal coverage and a rational amount of transportation subsidy should be proposed.
Rice black-streaked dwarf virus (RBSDV), a member of the genus Fijivirus within the family Reoviridae, causes severe damage to cereal crops in South East Asia. The protein P7-2, encoded by the second open reading frame of segment S7, is conserved among most plant-infecting fijiviruses, but its function is still obscure.
In this study, P7-2 was used as bait in two-hybrid screens of a cDNA library expressing Zea mays proteins. It was found that there is a strong interaction between P7-2 and Z. mays SKP1 (SKP1Maize), a core subunit of the multicomponent SCF (SKP1/Cullin1/F-box/Rbx1) E3 ubiquitin ligase. The interaction was then confirmed in leaf epidermal cells of Nicotiana benthamiana by bimolecular fluorescence complementation assay. Further investigations indicated that P7-2 also interacts with SKP1 proteins from other plants, including Arabidopsis thaliana, N. benthamiana,Oryza sativa and Saccharum sinense. The C-terminal fragment of SKP1Maize (residues 97–176) and the middle fragment of P7-2 (residues 79–214) are necessary to sustain the interaction, while the C-terminal putative α-helix domain spanning residues 214–295 of P7-2 greatly facilitates the interaction. Agrobacterium-mediated transient suppression assay showed that P7-2 has no obvious activity to suppress local RNA silencing.
Taken together, our results indicated that RBSDV P7-2 can interact with SKP1 proteins from different plants. This is the first report linking a Fijivirus protein to a component of the ubiquitin proteasome system. P7-2 might be a potential F-box protein encoded by RBSDV and involved in the plant-virus interaction through ubiquitination pathway.
Rice black-streaked dwarf virus; P7-2; SKP1; Interaction; SCF ubiquitin ligase
The aim of this study was to test whether a low dose of interferon-α-2b (IFN-α2b) enhances the clinical outcome of docetaxel (DXT) in patients with castration-resistant prostate cancer (CRPC). A prospective controlled trial of 40 CRPC patients receiving 5 mg of prednisone twice daily was conducted, where patients were randomly assigned to be administered 75 mg/m2 DXT plus 3 mIU/m2 IFN-α2b (group A, n=20) or 75 mg/m2 DXT alone (group B, n=20). The prostate-specific antigen (PSA) response, tumor response, progression-free survival (PFS) and overall survival (OS) were evaluated. There was no statistically significant difference in PSA response rate between groups A and B (65 vs. 47.4%, P=0.341). The tumor response rate in group A was significantly greater compared with that in group B (55 vs. 21.1%, P=0.048). The median PFS was longer in group A compared with that in group B (10 vs. 8 months, P=0.043). There was no statistically significant difference in median OS between the two groups (19 vs. 17 months, P=0.348), but one patient displayed a complete tumor response in group A. In groups A and B, transient grade 3 to 4 neutropenia was observed in nine and six patients, grade 3 to 4 anemia was observed in three and five patients, and grade 3 to 4 general fatigue was observed in four and one patient(s), respectively. The proportion of patients with grade 3 to 4 toxicity was not statistically different between the two groups. A low dosage of IFN-α2b may improve the antitumor activity of DXT with an acceptable toxicity profile in patients with CRPC.
castration-resistant prostate cancer; docetaxel; interferon-α-2b
The genus Gossypium is a globally important crop that is used to produce textiles, oil and protein. However, gossypol, which is found in cultivated cottonseed, is toxic to humans and non-ruminant animals. Efforts have been made to breed improved cultivated cotton with lower gossypol content. The delayed gland morphogenesis trait possessed by some Australian wild cotton species may enable the widespread, direct usage of cottonseed. However, the mechanisms about the delayed gland morphogenesis are still unknown. Here, we sequenced the first Australian wild cotton species (Gossypiumaustrale) and a diploid cotton species (Gossypiumarboreum) using the Illumina Hiseq 2000 RNA-seq platform to help elucidate the mechanisms underlying gossypol synthesis and gland development. Paired-end Illumina short reads were de novo assembled into 226,184, 213,257 and 275,434 transcripts, clustering into 61,048, 47,908 and 72,985 individual clusters with N50 lengths of 1,710 bp, 1544 BP and 1,743 bp, respectively. The clustered Unigenes were searched against three public protein databases (TrEMBL, SwissProt and RefSeq) and the nucleotide and protein sequences of Gossypiumraimondii using BLASTx and BLASTn. A total of 21,987, 17,209 and 25,325 Unigenes were annotated. Of these, 18,766 (85.4%), 14,552 (84.6%) and 21,374 (84.4%) Unigenes could be assigned to GO-term classifications. We identified and analyzed 13,884 differentially expressed Unigenes by clustering and functional enrichment. Terpenoid-related biosynthesis pathways showed differentially regulated expression patterns between the two cotton species. Phylogenetic analysis of the terpene synthases family was also carried out to clarify the classifications of TPSs. RNA-seq data from two distinct cotton species provide comprehensive transcriptome annotation resources and global gene expression profiles during seed germination and gland and gossypol formation. These data may be used to further elucidate various mechanisms and help promote the usage of cottonseed.
Background: The Pro12Ala polymorphism in the peroxisome Proliferator-activated receptor-gamma2 PPARγ2) gene that account for metabolic dysfunction in women with polycystic ovary syndrome (PCOS) remain elusive. Aim: To explore the association between PPARγ2 gene pro12ala polymorphism and the metabolic characteristics in Chinese women with PCOS. Methods: PPARγ2 gene Pro12Ala polymorphism was assayed by PCR/RFLP methods in 120 Chinese women with PCOS and 118 normal subjects. All subjects were examined by anthropometry, lipid profile, sex hormone, oral glucose tolerance tests and insulin tolerance tests. Results: In PCOS patients, women with the non-Pro/Pro genotypes of the PPARγ2 gene Pro12Ala polymorphism showed statistically significantly higher fasting triglycerides (TG) levels and WHR value than those with the Pro/Pro genotype (P=.006 for both). There was no significant difference with PPARγ2 Pro12Ala polymorphism distributions between Chinese Han women with PCOS and controls. Conclusion: PPARγ2 gene Pro12Ala polymorphism was not supposed to be susceptible genes in PCOS. However, in PCOS patients, the PPAR-gamma Pro12Ala polymorphism may modulate the concentrations of serum fasting TG levels and fat-deposition in abdomen, respectively.
Polycystic ovary syndrome; peroxisome proliferator-activated receptor-gamma2; polymorphism; central obesity; hypertriglyceridemia
Platelets are essential for primary hemostasis; however, platelet activation also plays an important proinflammatory role. Inflammation promotes the development of cardiac fibrosis and heart failure induced by hypertension. In this study, we aimed to determine whether inhibiting platelet activation using clopidogrel could inhibit hypertension-induced cardiac inflammation and fibrosis.
Using a mouse model of angiotensin II (Ang II) infusion (1,500 ng/[kg·min] for 7 days), we determined the role of platelet activation in Ang II infusion-induced cardiac inflammation and fibrosis using a P2Y12 receptor inhibitor, clopidogrel (50 mg/[kg·day]).
CD41 staining showed that platelets accumulated in Ang II-infused hearts. Clopidogrel treatment inhibited Ang II infusion-induced accumulation of α-SMA+ myofibroblasts and cardiac fibrosis (4.17 ± 1.26 vs. 1.46 ± 0.81, p < 0.05). Infiltration of inflammatory cells, including Mac-2+ macrophages and CD45+Ly6G+ neutrophils (30.38 ± 4.12 vs. 18.7 ± 2.38, p < 0.05), into Ang II-infused hearts was also suppressed by platelet inhibition. Real-time PCR and immunohistochemical staining showed that platelet inhibition significantly decreased the expression of interleukin-1β and transforming growth factor-β. Acute injection of Ang II or PE stimulated platelet activation and platelet-leukocyte conjugation, which were abolished by clopidogrel treatment.
Thus, inhibition of platelet activation by clopidogrel prevents cardiac inflammation and fibrosis in response to Ang II. Taken together, our results indicate Ang II infusion-induced hypertension stimulated platelet activation and platelet-leukocyte conjugation, which initiated inflammatory responses that contributed to cardiac fibrosis.
Clopidogrel; Platelet activation; Inflammation; Hypertension; Cardiac fibrosis
The activated nuclear factor-KappaB signaling pathway plays a critical role in inducing inflammatory injury. It has been reported that electroacupuncture could be an effective anti-inflammatory treatment. We aimed to explore the complex mechanism by which EA inhibits the activation of the NF-κB signal pathway and ameliorate inflammatory injury in the short term; the effects of NEMO Binding Domain peptide for this purpose were compared. Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats are in the study. The neurobehavioral scores, infarction volumes, and the levels of IL-1β and IL-13 were detected. NF-κB p65, IκBα, IKKα, and IKKβ were analyzed and the ability of NF-κB binding DNA was investigated. The EA treatment and the NBD peptide treatment both reduced infarct size, improved neurological scores, and regulated the levels of IL-1β and IL-13. The treatment reduced the expression of IKKα and IKKβ and altered the expression of NF-κB p65 and IκBα in the cytoplasm and nucleus; the activity of NF-κB was effectively reduced. We conclude that EA treatment might interfere with the process of NF-κB nuclear translocation. And it also could suppress the activity of NF-κB signaling pathway to ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion.
p27Kip1 is a key cell-cycle regulator whose level is primarily regulated by the ubiquitin–proteasome degradation pathway. Its β1 subunit is one of seven β subunits that form the β-ring of the 20S proteasome, which is responsible for degradation of ubiquitinated proteins. We report here that the β1 subunit is up-regulated in oesophageal cancer tissues and some ovarian cancer cell lines. It promotes cell growth and migration, as well as colony formation. β1 binds and degrades p27Kip1directly. Interestingly, the lack of phosphorylation at Ser158 of the β1 subunit promotes degradation of p27Kip1. We therefore propose that the β1 subunit plays a novel role in tumorigenesis by degrading p27Kip1.
degradation; p27Kip1; phosphorylation; tumorigenesis; β1 subunit; CBB, Coomassie Brilliant Blue; CDK, cyclin-dependent kinase; GST, glutathione transferase; HCC, hepatocellular carcinoma; HEK-293T, HEK-293 cells expressing the large T-antigen of SV40 (simian virus 40); PKA, protein kinase A; Rb, retinoblastoma; Rfp, red fluorescent protein; RP, regulatory particle; shRNA, small hairpin RNA
Sensitive and specific detection of liver cirrhosis is an urgent need for optimal individualized management of disease activity. Substantial studies have identified circulation miRNAs as biomarkers for diverse diseases including chronic liver diseases. In this study, we investigated the plasma miRNA signature to serve as a potential diagnostic biomarker for silent liver cirrhosis.
A genome-wide miRNA microarray was first performed in 80 plasma specimens. Six candidate miRNAs were selected and then trained in CHB-related cirrhosis and controls by qPCR. A classifier, miR-106b and miR-181b, was validated finally in two independent cohorts including CHB-related silent cirrhosis and controls, as well as non−CHB-related cirrhosis and controls as validation sets, respectively.
A profile of 2 miRNAs (miR-106b and miR-181b) was identified as liver cirrhosis biomarkers irrespective of etiology. The classifier constructed by the two miRNAs provided a high diagnostic accuracy for cirrhosis (AUC = 0.882 for CHB-related cirrhosis in the training set, 0.774 for CHB-related silent cirrhosis in one validation set, and 0.915 for non−CHB-related cirrhosis in another validation set).
Our study demonstrated that the combined detection of miR-106b and miR-181b has a considerable clinical value to diagnose patients with liver cirrhosis, especially those at early stage.
Adiponectin is a predominantly adipocyte-derived hormone which influences insulin sensitivity and energy homeostasis through at least two receptors, AdipoR1 and AdipoR2. In animal models, adiponectin may regulate ovarian steroidogenesis, folliculogenesis, and ovulation. The receptors AdipoR1 and AdipoR2 are present in the human ovary, but their regulation is unknown. In these studies, we determined the effects of LH receptor activation on the expression and function of the two adiponectin receptors in human granulosa cells.
Granulosa cells were obtained at the time of oocyte retrieval in women undergoing in vitro fertilization (IVF). Cells were isolated and cultured for 48 h in DMEM/F12 medium with 5 % FBS and 50 ug/ml gentamicin. Medium was changed to low serum for 12 h and cells were treated with hCG (100 ng/ml), forskolin (30 μMol/L), or FSH (1 IU/ml) for 24 h for mRNA experiments. mRNA was isolated and RT PCR was performed using Taqman assays and quantification with the delta delta CT method. For immunocytochemistry, cells were grown on chamber slides and treated with hCG for 1 to 24 h and fixed with acetone. ICC was performed with polyclonal rabbit primary antibodies followed by alexa fluor goat anti-rabbit antibody and imaging with a fluorescence microscope and Zeiss software analysis. 3β-hydroxysteroid dehydrogenase (3βHSD) enzyme activity was determined by measuring the progesterone produced when cells were provided with an excess of 22-hydroxy-cholesterol as substrate following an incubation with hCG (1 IU/ml) and/or adiponectin (10 ng/ml). Progesterone content in the media was determined by ELISA.
Messenger RNA for the two Adiponectin receptors is differentially regulated by activation of LHR with hCG treatment. AdipoR2 was increased nearly 4-fold (p < 0.05), whereas AdipoR1 expression was not changed by hCG treatment. Treatment with either FSH or forskolin (an activator of cAMP) had similar effects. Basal AdipoR2 protein was fairly low in granulosa cells in culture however treatment of cells with hCG resulted in a discernible increase in immunodetectable cytoplasmic protein as early as 6 h after treatment and was maintained for at least 24 h. The number of cells positive for AdipoR2 at 6 h increased from a basal of 20 % to almost 60 % (p < 0.05). Adiponectin treatment of hCG-primed cells resulted in increased 3βHSD activity by approximately 60 % over hCG alone and more than 3-fold over basal levels.
AdipoR2 is regulated by the LH receptor function via a cAMP dependant mechanism. Increased expression of adipoR2 prior to and following ovulation may contribute to enhanced 3βHSD activity and increased progesterone secretion by the corpus luteum of the ovary. Dysregulation of adiponectin that may occur with PCOS may impair normal progesterone production.
Ovary; Granulosa; Adiponectin; Adiponectin receptor; PCOS; Progesterone
Adiponectin, an abundant adipokine with insulin sensitizing properties, exists different multimeric forms, including low molecular weight (LMW), medium molecular weight (MMW), and high molecular weight (HMW) species. Alterations in the distribution of adiponectin multimers and the relationship between adiponectin multimers and insulin resistance (IR) in women with the polycystic ovary syndrome (PCOS) remain unclear. To compare adiponectin multimerization status and estimate of insulin sensitivity in Chinese women with PCOS compared with age and body mass index (BMI)-matched controls.
Cross-sectional study involving 64 Chinese women with PCOS and 59 normal women. Circulating total adiponectin and its multimeric forms were determined by ELISA and insulin resistance was estimated using the homeostasis assessment insulin resistance index (HOMA-IR).
After controlling for BMI status, levels of both total and HMW adiponectin were significantly lower in women with PCOS compared with normal women (P<0.05). Furthermore, HMW adiponectin provided a stronger contribution to models predicting insulin resistance than total adiponectin. Lastly, decreased HMW adiponectin was associated with increased HOMA-IR in both normal and PCOS women, and this association was independent of both overall adiposity and visceral adiposity.
Levels of both total and HMW adiponectin are decreased in Chinese women with PCOS compared with normal control women and the differences in HMW adiponectin persists after controlling for BMI. Furthermore, HMW adiponectin is a stronger predictor of insulin resistance in both women with PCOS and normal women than total adiponectin.
Polycystic ovary syndrome; adiponectin; insulin resistance; HMW-adiponectin
Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.
AIM: To investigate the effect of Danzhijiangtang capsule (DJC) on monocyte chemoattractant protein-1 (MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus (T2DM) subclinical vascular lesions.
METHODS: Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each. Oral antidiabetic therapy with routine western medicine was conducted in both groups, and the treatment group was additionally treated with DJCs. The treatment course for both groups was 12 wk. Before and after treatment, the total efficiency and traditional Chinese medicine (TCM) syndrome score were calculated. The fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), fasting insulin (FINS), insulin resistance index (IRI), hemoglobin (Hb)A1c, blood lipids, and hemorheology indices were determined. In addition, the levels of vascular endothelial growth factors including thrombomodulin (TM), von Willebrand factor (vWF), P-selectin and MCP-1 mRNA were determined.
RESULTS: After 12 wk of treatment, the TCM syndrome score was significantly decreased compared to before treatment in both groups. After treatment, FPG, 2hPG, HbA1c, FINS, IRI, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, whole blood low shear specific viscosity, plasma specific viscosity, TM, vWF, P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups. After treatment, the total efficiency and TCM syndrome score in the treatment group were better than in the control group. FINS, IRI, whole blood high shear specific viscosity, plasma specific viscosity, TM, vWF, P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.
CONCLUSION: DJCs are efficacious in supplementing qi, nourishing yin and invigorating blood circulation, and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.
Danzhijiangtang capsule; Type 2 diabetes mellitus; Subclinical vascular lesions; Monocyte chemoattractant protein-1
syndromic surveillance system has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation, and it is especially effective for surveillance in resource poor settings. However, most current syndromic surveillance systems are established in developed countries, and there are very few reports on the development of an electronic syndromic surveillance system in resource-constrained settings.
this study describes the design and pilot implementation of an electronic surveillance system (ISS) for the early detection of infectious disease epidemics in rural China, complementing the conventional case report surveillance system.
ISS was developed based on an existing platform ‘Crisis Information Sharing Platform’ (CRISP), combining with modern communication and GIS technology. ISS has four interconnected functions: 1) work group and communication group; 2) data source and collection; 3) data visualization; and 4) outbreak detection and alerting.
As of Jan. 31st 2012, ISS has been installed and pilot tested for six months in four counties in rural China. 95 health facilities, 14 pharmacies and 24 primary schools participated in the pilot study, entering respectively 74256, 79701, and 2330 daily records into the central database. More than 90% of surveillance units at the study sites are able to send daily information into the system. In the paper, we also presented the pilot data from health facilities in the two counties, which showed the ISS system had the potential to identify the change of disease patterns at the community level.
The ISS platform may facilitate the early detection of infectious disease epidemic as it provides near real-time syndromic data collection, interactive visualization, and automated aberration detection. However, several constraints and challenges were encountered during the pilot implementation of ISS in rural China.
The Basic Local Alignment Search Tool (BLAST) website at the National Center for Biotechnology (NCBI) is an important resource for searching and aligning sequences. A new BLAST report allows faster loading of alignments, adds navigation aids, allows easy downloading of subject sequences and reports and has improved usability. Here, we describe these improvements to the BLAST report, discuss design decisions, describe other improvements to the search page and database documentation and outline plans for future development. The NCBI BLAST URL is http://blast.ncbi.nlm.nih.gov.
Imp13, a member of importin-β superfamily, is found to be one of two bidirectional transport receptors in many nuclear transport activities in mammals. Several cargoes of imp13 have been identified; most of these are essential factors involved in cell cycle and development. The expression and localization of imp13 may influence its cargoes in playing their roles in appropriate time and space. To gain insight into the role of imp13 in brain development, we generated an anti-imp13 polyclonal antibody and investigated the expressions of imp13 in mouse embryonic brains during development, including E13.5, E15.5, E17.5, P0, and adult, at both transcriptional and translational levels. In addition, we performed immunohistochemical analysis and revealed that imp13 tends to be localized in the cytoplasm at the early stages and relocates into the nucleus at the late stages in neuronal cells of mouse brains. These findings suggested that the expression and localization of imp13 in brain tissues are regulated developmentally, which extends our knowledge of the dynamic presence of imp13. These observations also imply that imp13 contributes to the neural cell-specific cargo trafficking and potentially to other functions during brain development.
Importin13 (impl3); Imp13 antibody; Brain development; Expression; Localization
Homeodomain proteins are crucial transcription factors for cell differentiation, cell proliferation and organ development. Interestingly, their homeodomain signature structure is important for both their DNA-binding and their nucleocytoplasmic trafficking. The accurate nucleocytoplasmic distribution of these proteins is essential for their functions. We summarize information on a) the roles of karyopherins for import and export of homeoproteins, b) the regulation of their nuclear transport during development, and c) the corresponding complexity of homeoprotein nucleocytoplasmic transport signals.
Homeodomain; homeoprotein; nuclear transport; importin α; karyopherin β; NLS; NES; development; regulation
To develop and test the method of incorporating different control bars for outbreak detection in syndromic surveillance system.
Aberration detection methods are essential for analyzing and interpreting large quantity of nonspecific real-time data collected in syndromic surveillance system. However, the challenge lies in distinguishing true outbreak signals from a large amount of false alarm (1). The joint use of surveillance algorithms might be helpful to guide the decision making towards uncertain warning signals.
A syndromic surveillance project (ISSC) has been implemented in rural Jiangxi Province of China since August 2011. Doctors in the healthcare surveillance units of ISSC used an internet-based electronic system to collect information of daily outpatients, which included 10 infectious related symptoms. From ISSC database, we extracted data of fever patients reported from one township hospital in GZ town between August 1st and December 31st, 2011 to conduct an exploratory study. Six different control bar algorithms, which included Shewart, Moving Average (MA), Exponentially Weighted Moving Average (EWMA) and EARS’ C1, C2, C3, were prospectively run among historical time series of daily fever count to simulate a real-time outbreak detection. Each control bar used 7 days’ moving baseline with a lag of 2 days [the baseline for predicting Day(t) starts from Day(t-9) to Day(t-3), C1 method used a lag of zero day]. We set the threshold of μ+2σ for Shewart and MA, and 2.1 for EWMA C1, C2 and C3. An alarm was triggered when the observed data exceeded threshold, and the detailed information of each patient were checked for signal verification. Microsoft Excel 2007 was used to calculate the simulation results.
During the 5 months, GZ township hospital reported 514 outpatients with fever symptom, with an average of 3.4 per day. All control bars were simultaneously operated among daily counts of fever cases. Of the 153 days on surveillance, 29 triggered alarms by at least one of the control bars. Nine days triggered alarms from >= 3 control bars while on one day (12/30) all 6 algorithms raised alarms. Figure 1 shows the date, fever count, algorithm and warning level (color) of each alarm, which we called a control bar matrix. It can be seen that C3 and EWMA present a higher sensitiveness towards tiny data change whereas C1, C2 and MA focus on large increase of data. C3 also had a memory effect on recent alarms. No infectious disease epidemic or outbreak event was confirmed within the signals. Most fever patients on the nine high-warning days (red and purple) were diagnosed as upper level respiratory infection. However, we discovered that the sharp increase of fever cases on 12/30 was attributed to 5 duplicate records mistakenly input by the staff in GZ hospital.
By combining control bars with different characteristics, the matrix has potential ability to improve the specificity of detection while maintaining a certain degree of sensitivity. With alarms categorized into hierarchical warning levels, public health staffs can decide which alarm to investigate according to the required sensitivity of surveillance system and their own capacity of signal verification. Though we did not find any outbreak event in the study, the possibility of localized influenza epidemic on high-warning days cannot be wiped out, and the matrix’s ability to detect abnormal data change was apparent. The proper combination, baseline and threshold of control bars will be further explored in the real-time surveillance situation of ISSC.
Syndromic surveillance; matrix; control bar; signal
To understand the structure and capacity of current infection disease surveillance system, and to provide baseline information for developing syndromic surveillance system in rural China.
To meet the long-term needs of public health and social development of China, it is in urgency to establish a comprehensive response system and crisis management mechanism for public health emergencies. Syndromic surveillance system has great advantages in promoting early detection of epidemics and reducing the burden of disease outbreak confirmation (1). The effective method to set up the syndromic surveillance system is to modify existing case report system, improve the organizational structures and integrate new function with the traditional system.
Since August 2011, an integrated syndromic surveillance project (ISSC) has been implemented in China. Before the launching of the project, a cross-sectional study was carried out in Fengxin County and Yongxiu County of Jiangxi province during October 11 to 18, 2010. Institution information were investigated in the county hospital, township hospital and County Center for Disease Control and Prevention (CDC) to understand the performance of existing case report system for notifiable infectious diseases with regard to its structure, capacity and data collection procedure. Health care workers from each township hospital and village health station were questionnaire interviewed for information on qualification of human resources, basic healthcare delivery condition, hardware and software needs for ISSC.
An internet-based real-time (quasi real-time) case report system for notifiable infectious diseases, based on the three-tier public health service System, had been established in these two counties since 2004. The farthest end of net user in case report system was township hospital. Blood routine test, urine routine test, B ultrasound and electrocardiogram were available in all township hospitals. There was no laboratory equipment in village health stations in these two counties. All the township hospitals in these two counties were equipped with land-line telephones and desktop computers. The internet covers all township hospitals in both counties. Most clinical doctors in township hospital(TH) and village health station(VHS) were male. The age of doctors ranged from 21 to 72 years old, with the average at 42 and median at 40 years. The village health workers were significantly older, less educated and served in health care longer than the township hospital doctors. In Yongxiu County, 95.6% of the village health stations were equipped with computers, including private-owned computers, and 80.7% of them had access to the internet; while in Fengxin County, 66.5% of the village health stations possessed computers, among which most were private property of village doctors, and only 44.2% of them had access to the internet.
The current case report system, with full coverage and stable human resource, has established a solid basis for developing syndromic surveillance system in rural China. The syndromic surveillance system could play its role in early detection of infectious disease outbreaks in rural area where laboratory service for infectious disease diagnosis are not available. However, the lack of computerized patient registration in village and township health care facilities and incomplete internet coverage in rural area and relatively low quality of human resource in village level should be taken into consideration seriously before establishing the syndromic surveillance system in rural China.
Syndromic surveillance; rural area; human resources; case report system
To describe and explore the spatial and temporal variability via ZIMM for absenteeism surveillance in primary school for early detection of infectious disease outbreak in rural China.
Absenteeism has great advantages in promoting the early detection of epidemics1. Since August 2011, an integrated syndromic surveillance project (ISSC) has been implemented in China2. Distribution of the absenteeism generally are asymmetry, zero inflation, truncation and non-independence3. For handling these encumbrances, we should apply the Zero-inflated Mixed Model (ZIMM).
Data for this study was obtained from the web-based data of ISSC in 62 primary schools in two counties of Jiangxi province, China from April 1th, 2012 to June 30st, 2012. The ZIMM was used to explore: 1)the temporal and spatial variability regarding occurrence and intensity of absenteeism simultaneously, and 2) the heterogeneity among the reporting primary schools by introducing random effects into the intercepts. The analyse was processed in the SAS procedure NLMIXED4.
The total 4914 absenteeism events were reported in the 62 primary schools in the study period. The rate of zero report was 49.88% (Fig. 1). According to ZIMM, there are fixed and random effect parameters in this model (Table 1). Firstly, for the fixed parameters, the spatial variable (county) was not significantly different both the occurrence and intensity model, while for the temporal variable (month), the probability of absenteeism occurrence was significantly different over three months (β=−0.165, p =0.026), suggesting a decreasing of school absenteeism from April to June. Meanwhile, a statistical significant difference in the intensity of absenteeism was also found over the three months (β=−0.073, p=0.007). Secondly, the random effect of intensity model was statistically significance (p=0.008), which strongly indicated a heterogeneity in intensity of absenteeism among the surveillance schools. Whereas the random effect of occurrence model by logistic regression showed a non-statistical difference (p=0.774) among the schools suggesting the homogeneity in the occurrence of absenteeism.
School absenteeism data has greater uncertain than many other sources and easier fluctuate by some factors such as holiday, season, family status and geographic distribution. Thus, the spatial and temporal dynamics should be taken into account in controlling fluctuate of absenteeism. Moreover, school absenteeism data are correlated within each school due to repeated measures. Applying the ZIMM, the occurrences and intensity of absenteeism could be evaluated to reduce the bias and improve the prediction precision. The ZIMM is an appropriate tool for health authorities in decision making for public health events.
surveillance; absenteeism; zero-inflated mixed model; occurrence; intensity
Background: The pathogenic factors that account for the development of diabetes condition in Chinese women with polycystic ovary syndrome (PCOS) remain elusive. Aim: To clarify the pathogenic features by evaluating the levels of insulin sensitivity and β cell function in these women with PCOS, either separately or by using of a disposition indexes (DIs). Methods: Cross-sectional study involving 137 Chinese women with PCOS and 123 normal women were examined by anthropometry, lipid profile, sex hormone, high-sensitivity C reactive protein, oral glucose tolerance tests and insulin tolerance tests. Results: After controlling for BMI status, the Matsuda Index was significantly lower in women with PCOS in comparison to those of normal women (p<0.000). The early phase of insulin secretion (insulinogenic index) remained significantly lower in lean women with PCOS(LP) than those of both lean and obese women of control group (p=0.007, and p = 0.01, respectively). The mean HOMA-F values were significantly lower (p =0.045) in obese women with PCOS (OP) than those of BMI-matched women. Further, all DIs derived from non-fasting state indexes in women with PCOS were significantly lower than those of BMI-matched control women (p<0.001 for all). Lastly, DIs derived from fasting states indexes in OP were significantly lower than those of LP. Conclusion: Early impaired β cell function was detected in both LP and OP. However, more serious primary defect in insulin action was detected in LP compared to OP. These findings imply that early screening and intervention for PCOS would be therapeutic for Chinese women.
Polycystic ovary syndrome; insulin resistance; early phase secretion of insulin
Numblike, a negative regulator in glioma cell migration and invasion, was found to mediate nuclear factor kappa B activation by suppressing tumor necrosis factor receptor–associated factor 5.
The Notch signaling regulator Numblike (Numbl) is expressed in the brain, but little is known regarding its role in the pathophysiology of glial cells. In this paper, we report that Numbl expression was down-regulated in high-grade human glioma tissue samples and glioblastoma cell lines. To investigate the role of Numbl in glioma migration and invasion, we generated human glioma cell lines in which Numbl was either overexpressed or depleted. Overexpression of Numbl suppressed, while elimination of Numbl promoted, the migration and invasion of glioma cells. Numbl inhibited glioma migration and invasion by dampening NF-κB activity. Furthermore, Numbl interacted directly with tumor necrosis factor receptor–associated factor 5 (TRAF5), which signals upstream and is required for the activation of NF-κB, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5. In conclusion, our data suggest that Numbl negative regulates glioma cell migration and invasion by abrogating TRAF5-induced activation of NF-κB.
MicroRNAs have been implicated in the regulation of several cellular signaling pathways of colorectal cancer (CRC) cells. Although emerging evidence proves that microRNA (miR)-106a is expressed highly in primary tumor and stool samples of CRC patients; whether or not miR-106a mediates cancer metastasis is unknown. We show here that miR-106a is highly expressed in metastatic CRC cells, and regulates cancer cell migration and invasion positively in vitro and in vivo. These phenotypes do not involve confounding influences on cancer cell proliferation. MiR-106a inhibits the expression of transforming growth factor-β receptor 2 (TGFBR2), leading to increased CRC cell migration and invasion. Importantly, miR-106a expression levels in primary CRCs are correlated with clinical cancer progression. These observations indicate that miR-106a inhibits the anti-metastatic target directly and results in CRC cell migration and invasion.
Human papillomavirus (HPV) infection causes cervical cancer and premalignant lesions of the cervix. Prevalence of HPV infection and HPV genotypes vary among different regions. However there is no data on the prevalence of HPV infection and HPV genotypes from southwest China. This study was undertaken to determine the prevalence of and risk factors for HR-HPV infection in Qujing of Yunnan province, southwest China to provide comprehensive baseline data for future screening strategies.
A sample of 5936 women was chosen by the multi-stage stratified cluster sampling method with selection probabilities proportional to size (PPS). An epidemiological questionnaire was conducted via a face-to-face interview and cervical specimens were taken for HPV DNA testing by Digene Hybrid Capture 2 (HC2) test. HPV Genotyping Reverse Hybridization Test was used for HPV genotyping. Proportions were compared by Chi-squared tests, and logistic regression was utilized to evaluate risk factors.
The median age was 38 years and the inter-quartile range was from 31 years to 47 years. 97.3% of the study population was Han nationality. Overall prevalence of HR-HPV infection was 8.3% (494/5936) and bimodal age distribution of HPV infection was observed. The five most prevalent HR-HPV genotypes were HPV-16(3.4%), HPV-56(1.7%), HPV-58(1.4%), HPV-33(1.2%) and HPV-52(0.88%). Multiple HPV infections were identified in 50.5% (208/412) of the positive genotyping specimens. Multivariate logistic regression model indicated that parity (OR = 1.35, 95% CI: 1.18-1.53, p < 0.0001) was a risk factor for HR-HPV infection, and age of 50–65 years (OR = 0.60, 95% CI: 0.45-0.80, p = 0.0005), being married or in stable relationship (OR = 0.55, 95% CI: 0.31-0.96, p = 0.035) were protective factors.
This study provided baseline data on HR-HPV prevalence in the general female population in Qujing of Yunnan province, southwest China. The finding of multiple HPV infections and bimodal age distribution revealed that HPV screening is necessary for perimenopausal women in future.
Human papillomavirus; Genotype; Cervix; Epidemiology; China