Genetic approaches to analyzing neuronal circuits and learning would benefit from a technology to first deliver a specific gene into presynaptic neurons, and then deliver a different gene into an identified subset of their postsynaptic neurons, connected by a specific synapse type. Here, we describe targeted gene transfer across a neocortical glutamatergic synapse, using as the model the projection from rat postrhinal to perirhinal cortex. The first gene transfer, into the presynaptic neurons in postrhinal cortex, used a virus vector and standard gene transfer procedures. The vector expresses an artificial peptide neurotransmitter containing a dense core vesicle targeting domain, a NMDA NR1 subunit binding domain (from a monoclonal antibody), and the His tag. Upon release, this peptide neurotransmitter binds to NMDA receptors on the postsynaptic neurons. Antibody-mediated targeted gene transfer to these postsynaptic neurons in perirhinal cortex used a His tag antibody, as the peptide neurotransmitter contains the His tag. Confocal microscopy showed that with untargeted gene transfer, ~3 % of the transduced presynaptic axons were proximal to a transduced postsynaptic dendrite. In contrast, with targeted gene transfer, ≥20 % of the presynaptic axons were proximal to a transduced postsynaptic dendrite. Targeting across other types of synapses might be obtained by modifying the artificial peptide neurotransmitter to contain a binding domain for a different neurotransmitter receptor. This technology may benefit elucidating how specific neurons and subcircuits contribute to circuit physiology, behavior, and learning.
glutamatergic synapse; vesicular glutamate transporter 1 promoter; peptide neurotransmitter; antibody-mediated targeted gene transfer; herpes simplex virus vector
A network approach to brain and dynamics opens new perspectives towards understanding of its function. The functional connectivity from functional MRI recordings in humans is widely explored at large scale, and recently also at the voxel level. The networks of dynamical directed connections are far less investigated, in particular at the voxel level. To reconstruct full brain effective connectivity network and study its topological organization, we present a novel approach to multivariate Granger causality which integrates information theory and the architecture of the dynamical network to efficiently select a limited number of variables. The proposed method aggregates conditional information sets according to community organization, allowing to perform Granger causality analysis avoiding redundancy and overfitting even for high-dimensional and short datasets, such as time series from individual voxels in fMRI. We for the first time depicted the voxel-wise hubs of incoming and outgoing information, called Granger causality density (GCD), as a complement to previous repertoire of functional and anatomical connectomes. Analogies with these networks have been presented in most part of default mode network; while differences suggested differences in the specific measure of centrality. Our findings could open the way to a new description of global organization and information influence of brain function. With this approach is thus feasible to study the architecture of directed networks at the voxel level and individuating hubs by investigation of degree, betweenness and clustering coefficient.
Primary liver cancer and liver metastases are among the most frequent malignancies worldwide, with an increasing number of new cases and deaths every year. Traditional surgery is only suitable for a limited proportion of patients and imaging-guided percutaneous thermal ablation has achieved optimistic results for management of hepatic malignancy. This synopsis outlines the first clinical practice guidelines for ultrasound-guided percutaneous microwave ablation therapy for hepatic malignancy, which was created by a joint task force of the Society of Chinese Interventional Ultrasound. The guidelines aim at standardizing the microwave ablation procedure and therapeutic efficacy assessment, as well as proposing the criteria for the treatment candidates.
Practice guidelines; Microwave radiation; Catheter ablation; Liver cancer; Ultrasound
Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm-blooded animals, including both mammals and birds. Protein disulfide isomerase (PDI) localises to the surface of T. gondii tachyzoites and modulates the interactions between parasite and host cells. In this study, the protective efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T. gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified from Escherichia coli. Five groups of animals (10 animals/group) were immunised with 10, 20, 30, 40 μg of rTgPDI per mouse or with PBS as a control group. All immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks after the last immunisation, the immune responses were evaluated by lymphoproliferative assays and by cytokine and antibody measurements. The immunised mice were challenged with tachyzoites of the virulent T. gondii RH strain on the 14th day after the last immunisation. Following the challenge, the tachyzoite loads in tissues were assessed, and animal survival time was recorded. Our results showed that the group immunised with 30 μg rTgPDI showed significantly higher levels of specific antibodies against the recombinant protein, a strong lymphoproliferative response and significantly higher levels of IgG2a, IFN-gamma (IFN-γ), IL-2 and IL-4 production compared with other doses and control groups. While no changes in IL-10 levels were detected. After being challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and liver tissues from the rTgPDI group were significantly reduced compared with those of the control group, and the survival time of the mice in the rTgPDI group was longer than that of mice in the control group. Our results showed that immunisation with rTgPDI elicited a protective immune reaction and suggested that rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis.
AIM: To assess esophageal motility after esophageal endoscopic submucosal dissection (ESD).
METHODS: Twelve patients (6 men and 6 women) aged 53-64 years (mean age, 58 years) who underwent regular examination 3-12 mo after esophageal ESD for neoplasms of the esophageal body were included in this study. The ESD procedure was performed under deep sedation using a combination of propofol and fentanyl, and involved a submucosal injection to lift the lesion and use of a dual-knife and an insulated-tip knife to create a circumferential incision around the lesion extending into the submucosa. Esophageal motility was examined using a high-resolution manometry system. Dysphagia was graded using a five-point scale according to the Mellow and Pinkas scoring system. Patient symptoms and the results of esophageal manometry were then analyzed.
RESULTS: Of the 12 patients enrolled, 1 patient had grade 2 dysphagia, 1 patient had grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Ineffective esophageal motility was observed in 5 of 6 patients with above semi-circumference of resection extension. Of these 5 patients, 1 patient complained of grade 2 dysphagia (with esophageal stricture), one patient complained of grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Normal esophageal body manometry was observed in all 6 patients with below semi-circumference of resection extension. The 6 patients with normal esophageal motility did not complain of dysphagia.
CONCLUSION: Extensive esophageal ESD may cause esophageal dysmotility in some patients, and might also have an influence on dysphagia although without esophageal stricture.
Esophageal neoplasm; Endoscopic submucosal dissection; Dysphagia; Ineffective esophageal motility; Esophageal manometry
Primary restless leg syndrome (RLS) is a common sensory-motor disorder that is characterized by an irresistible urge to move the limbs and unpleasant sensations in the legs, which affects 1.9%–4.6% adults. Pramipexole, a potent dopamine D2/3 agonist, is recommended as “effective” in the short-term and “possibly effective” in the long-term treatment of primary RLS in the European guidelines on management of RLS. In this meta-analysis, we summarized the efficacy and tolerability of pramipexole in treatment for primary RLS. Results of this meta-analysis showed a favorable effect of pramipexole versus placebo on RLS symptoms (mean change on International RLS Study Group Rating Scale [IRLS] score: mean difference [MD] = −5.96; 95% confidence interval [CI]: −7.79 to −4.41, P < 0.00001) and sleep quality (pooled standard mean difference [SMD] = −0.48, 95% CI: −0.61 to −0.35, P < 0.00001). Nausea (relative risk [RR] = 2.68, 95% CI: 1.82 to 3.95, P < 0.001) and fatigue (RR = 1.82, 95% CI: 1.14 to 2.93, P = 0.013) were the most common adverse events, but, by and large, pramipexole was well-tolerated in patients with primary RLS. Nevertheless, long-term studies and more evidence of head-to-head comparisons of pramipexole with other dopamine agonists, anticonvulsants, and levodopa are needed.
restless legs syndrome; pramipexole; meta-analysis
Intercellular ligand-receptor recognitions are crucial natural interactions that initiate a number of biological and pathological events. We present here the simple construction of a unique class of biomimetic interfaces based on a graphene-mediated self-assembly of glycosyl anthraquinones to a screen-printed electrode for the detection of transmembrane glycoprotein receptors expressed on a hepatoma cell line. We show that an electroactive interface confined with densely clustered galactosyl ligands is able to ingeniously recognize the asialoglycoprotein receptors on live Hep-G2 cells employing simple electrochemical techniques. The only facility used is a personal laptop in connection with a cheap and portable electrochemical workstation.
The Fanconi anemia (FA) protein network is necessary for repair of DNA interstrand crosslinks (ICLs), but its control mechanism remains unclear. Here we show that the network is regulated by a ubiquitin signaling cascade initiated by RNF8 and its partner, UBC13; and mediated by FAAP20, a component of the FA core complex. FAAP20 preferentially binds the ubiquitin product of RNF8-UBC13; and its recruitment to ICLs requires this ubiquitin-binding activity, RNF8 and UBC13. Both RNF8 and FAAP20 are required for recruitment of FA core complex and FANCD2 to ICLs, whereas RNF168 can modulate efficiency of the recruitment. RNF8 and FAAP20 are needed for efficient FANCD2 monoubiquitination, a key step of the FA network; RNF8 and FA core complex work in the same pathway to promote cellular resistance to ICLs. Thus, the RNF8-FAAP20 ubiquitin cascade is critical for recruiting FA core complex to ICLs and for normal function of the FA network.
RNF8; FAAP20; RNF168; UBC13; Fanconi Anemia; ubiquitin
Several members of the let-7 microRNA family are downregulated in ovarian and other cancers. They are thought to act as tumor suppressors by lowering growth-promoting and anti-apoptotic proteins. In order to measure cellular let-7 levels systematically, we have developed a highly sensitive let-7 reporter assay system based on the expression of a chimeric mRNA that contains the luciferase coding region and a 3′-untranslated region (UTR) bearing two let-7-binding sites. In cells expressing the reporter construct, termed pmirGLO-let7, luciferase activity was high when let-7 was absent, while luciferase activity was low when let-7 levels were elevated. The ovarian cancer cell lines BG-1 and UCI-101 were transfected with the let-7 reporter and surveyed with a library of kinase inhibitors in order to identify pathways affecting let-7 activity. Among the inhibitors causing changes in endogenous let-7 abundance, the lowering of glycogen synthase kinase 3 (GSK-3)β function specifically increased let-7 levels and lowered luciferase activity. Similarly, silencing GSK-3β increased both mature and primary-let-7 levels in BG-1 cells, and decreased BG-1 cell survival. Further studies identified p53 as a downstream effector of the GSK-3β-mediated repression of let-7 biosynthesis. Our studies highlight GSK-3β as a novel therapeutic target in ovarian tumorigenesis.
Here, we present the first report of a novel rearranged porcine circovirus type 2 (PCV2) strain named BIV, isolated from both in vitro and in vivo sources. The complete circular genome of BIV is 896 nucleotides in length. The data will help us to update current knowledge of the replication of PCV2 viruses in cell culture and of their molecular evolution, as well as their diagnosis.
Psychogenic non-epileptic seizures (PNES) are paroxysmal behaviors that resemble epileptic seizures but lack abnormal electrical activity. Recent studies suggest aberrant functional connectivity involving specific brain regions in PNES. Little is known, however, about alterations of topological organization of whole-brain functional and structural connectivity networks in PNES. We constructed functional connectivity networks from resting-state functional MRI signal correlations and structural connectivity networks from diffusion tensor imaging tractography in 17 PNES patients and 20 healthy controls. Graph theoretical analysis was employed to compute network properties. Moreover, we investigated the relationship between functional and structural connectivity networks. We found that PNES patients exhibited altered small-worldness in both functional and structural networks and shifted towards a more regular (lattice-like) organization, which could serve as a potential imaging biomarker for PNES. In addition, many regional characteristics were altered in structural connectivity network, involving attention, sensorimotor, subcortical and default-mode networks. These regions with altered nodal characteristics likely reflect disease-specific pathophysiology in PNES. Importantly, the coupling strength of functional-structural connectivity was decreased and exhibited high sensitivity and specificity to differentiate PNES patients from healthy controls, suggesting that the decoupling strength of functional-structural connectivity might be an important characteristic reflecting the mechanisms of PNES. This is the first study to explore the altered topological organization in PNES combining functional and structural connectivity networks, providing a new way to understand the pathophysiological mechanisms of PNES.
Dysfunction of cardiac mitochondria appears to play a substantial role in cardiomyopathy or myocardial dysfunction and is a promising therapeutic target for many cardiovascular diseases. We investigated the effect of the Rho/Rho-associated protein kinase (ROCK) inhibitor fasudil on cardiac mitochondria from rats in which diabetes was induced by a combination of streptozotocin (STZ) and a sustained high-fat diet. Eight weeks after diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ followed by a sustained high-fat diet, either fasudil (5 mg/kg bid) or equivalent volumes of saline (control) were administered over four weeks. Fasudil significantly protected against the histopathologic changes of cardiac mitochondria in diabetic rats. Fasudil significantly reduced the abundances of the Rho A, ROCK 1, and ROCK 2 proteins, restored the activities of succinate dehydrogenase (SDH) and monoamine oxidase (MAO) in cardiac mitochondria, inhibited the opening of the mitochondrial permeability transition pore, and decreased the total antioxidant capacity, as well as levels of malonyldialdehyde, hydroxy radical, reduced glutathione, and superoxide dismutase in heart. Fasudil improved the structures of cardiac mitochondria and increased both SDH and MAO activities in cardiac mitochondria. These beneficial effects may be associated with the attenuation of oxidative stress caused by fasudil treatment.
Neuroblastoma is a childhood tumor in which transient therapeutic responses are typically followed by recurrence with lethal chemoresistant disease. In this study, we characterized the apoptotic responses in diverse neuroblastomas using an unbiased mitochondrial functional assay. We defined the apoptotic set-point of neuroblastomas using responses to distinct BH3 death domains providing a BH3 response profile, and directly confirmed survival dependencies. We found that viable neuroblastoma cells and primary tumors are primed for death with tonic sequestration of Bim, a direct activator of apoptosis, by either Bcl-2 or Mcl-1, providing a survival dependency that predicts the activity of Bcl-2 antagonists. The Bcl-2/Bcl-xL/Bcl-w inhibitor ABT-737 showed single agent activity against only Bim:Bcl-2 primed tumor xenografts. Durable complete regressions were achieved in combination with non-curative chemotherapy even for highest-risk molecular subtypes with MYCN amplification and activating ALK mutations. Furthermore, the use of unique isogenic cell lines from patients at diagnosis and at the time of relapse showed that therapy resistance was not mediated by upregulation of Bcl-2 homologues or loss of Bim priming, but by repressed Bak/Bax activation. Together, our findings provide a classification system that identifies tumors with clinical responses to Bcl-2 antagonists, defines Mcl-1 as the principal mediator of Bcl-2 antagonist resistance at diagnosis, and isolates the therapy resistant phenotype to the mitochondria.
Bcl-2 homology proteins; mitochondrial profiling; animal models; Bcl-2 antagonist
In recent years, a disease caused by Southern rice black-streaked dwarf virus (SRBSDV) has resulted in significant loss in rice production in Southern China and has spread quickly throughout East and Southeast Asia. This virus is transmitted by an insect vector, white-backed planthopper (WBPH) Sogatella furcifera (Hemiptera: Delphacidae), in a persistent propagative manner. Aside from rice, SRBSDV can also infect numerous Poaceae plants. However, the molecular mechanism of interaction between SRBSDV and its plant or insect vector remains unclear. In order to address this, we investigated the whole viral genome relative mRNA expression level in distinct hosts and monitored their expression level in real-time in rice plants.
In this study, a reliable, rapid, and sensitive method for detecting viral gene expression transcripts is reported. A SYBR Green I based real-time polymerase chain reaction (PCR) method was adopted for the quantitative detection of SRBSDV gene expression in different hosts and real-time changes in gene expression in rice.
Compared to the relative mRNA expression level of the whole genome of SRBSDV, P3, P7-1, and P9-2 were dominantly expressed in rice and WBPH. Similarly, these genes also exhibited high expression levels in corn, suggesting that they have more important functions than other viral genes in the interaction between SRBSDV and hosts, and that they could be used as molecular detection target genes of SRBSDV. In contrast, the levels of P6 and P10 were relative low. Western blotting analysis partially was also verified our qPCR results at the level of protein expression. Analysis of the real-time changes in SRBSDV-infected rice plants revealed four distinct temporal expression patterns of the thirteen genes. Moreover, expression levels of P1 and other genes were significantly down-regulated on days 14 and 20, respectively.
SRBSDV genes showed similar expression patterns in distinct hosts (rice, corn, and WBPH), indicating that SRBSDV uses the same infection strategy in plant and insect hosts. P3, P7-1, and P9-2 were the dominantly expressed genes in the three tested hosts. Therefore, they are likely to be genes with the most crucial function and could be used as sensitive molecular detection targets for SRBSDV. Furthermore, real-time changes in SRBSDV genes provided a basis for understanding the mechanism of interaction between SRBSDV and its hosts.
Southern rice black-streaked dwarf virus; Viral gene expression; Real-time quantitative polymerase chain reaction; Rice; Corn; White-backed planthopper; Real-time changes
We deciphered the genome of Yersinia pestis strain 2501, isolated from the Junggar Basin, a newly discovered great gerbil plague focus in Xinjiang, China. The total length of assembly was 4,597,322 bp, and 4,265 coding sequences were predicted within the genome. It is the first Y. pestis genome from this plague focus.
Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence.
Discoidin domain receptor 2 (DDR2) is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.
Long-term expression from helper virus-free Herpes Simplex Virus (HSV-1) vectors is required for many specific neural gene therapies and studies on neuronal physiology. We previously developed a promoter that supports long-term, neuron-specific expression by fusing the chicken ß-globin insulator (INS), followed by an upstream enhancer from the rat tyrosine hydroxylase (TH) promoter, to a neurofilament heavy gene (NFH) promoter. Here, we examined the capability of specific transcription factors to further improve long-term expression from this promoter. Following a HSV-1 virus infection, the virus genome is localized to promyelocytic leukemia protein (PML) nuclear bodies (NB). At these sites, specific cellular transcription factors interact with HSV-1 encoded transcription factors, and together regulate HSV-1 gene expression. Importantly, lysine-specific demethylase-1 (LSD1), CLOCK, and Co-Rest each activate HSV-1 gene expression. However, gene expression from HSV-1 vectors differs in a number of important aspects from the virus, including no HSV-1 genes are expressed. Nonetheless, these observations raise the possibility that specific transcription factors may improve long-term expression from specific promoters in HSV-1 vectors. Here, we show that overexpression of either LSD1 or CLOCK improves long-term expression from the INS-TH-NFH promoter, but overexpression of Co-Rest supports levels of long-term expression similar to those supported by a control vector. Further, overexpression of LSD1 is compatible with neuron-specific expression. Thus, overexpressing specific transcription factors can improve long-term expression from specific cellular promoters in HSV-1 vectors, and the chromatin structure of the vector has an important role in enabling expression.
herpes simplex virus vector; long-term expression; transcription factor; chromatin modifying enzyme; enhancer; striatal neuron
We report here for the first time the genome sequence of a rearranged porcine circovirus type 2 (PCV2) strain, CH-IVT1, isolated from PCV2-infected PK-15 cells. The complete circular genome of the CH-IVT1 is 605 nucleotides (nt) in length. The finding will help us to understand the molecular evolution of PCV2 and the relationship between PCV2 and PCV-associated diseases.
To understand the regulation mechanism of NaCl on glucosinolate metabolism in broccoli sprouts, the germination rate, fresh weight, contents of glucosinolates and sulforaphane, as well as myrosinase activity of broccoli sprouts germinated under 0, 20, 40, 60, 80, and 100 mmol/L of NaCl were investigated in our experiment. The results showed that glucoerucin, glucobrassicin, and 4-hydroxy glucobrassicin in 7-d-old broccoli sprouts were significantly enhanced and the activity of myrosinase was inhibited by 100 mmol/L of NaCl. However, the total glucosinolate content in 7-d-old broccoli sprouts was markedly decreased although the fresh weight was significantly increased after treatment with NaCl at relatively low concentrations (20, 40, and 60 mmol/L). NaCl treatment at the concentration of 60 mmol/L for 5 d maintained higher biomass and comparatively higher content of glucosinolates in sprouts of broccoli with decreased myrosinase activity. A relatively high level of NaCl treatment (100 mmol/L) significantly increased the content of sulforaphane in 7-d-old broccoli sprouts compared with the control. These results indicate that broccoli sprouts grown under a suitable concentration of NaCl could be desirable for human nutrition.
Glucosinolates; Brassica oleracea; Sulforaphane; Myrosinase; NaCl
Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor β. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC).
In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib.
Tumor growth and pulmonary metastasis were significantly suppressed in an orthotopic HCC model. Immunoblotting revealed that among known dovitinib targets, only PDGFR-β was expressed in two HCC cell lines, while four of five endothelial lines expressed PDGFR-β, FGFR-1, and VEGFR-2. Dovitinib inhibited endothelial cell proliferation and motility at 0.04 μmol/L, a pharmacologically relevant concentration; it was unable to inhibit the proliferation or motility of HCC cells at the same concentration. Immunohistochemical analyses showed that dovitinib significantly decreased the microvessel density of xenograft tumors, inhibiting proliferation and inducing apoptosis in HCC cells.
Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells.
Dovitinib; Endothelial cells; Hepatocellular carcinoma; Tumor growth; Tumor metastasis
Breast ductal cancer in situ (DCIS) can recur or progress to invasive ductal cancer (IDC), and the interim stage include DCIS with microinvasion (DCIS-Mi). In this article, we attempt to study the study the differences of clinicopathological features, imaging data, and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and IDC.
In this retrospective study, we attempt to compare the clinicopathological features, immunohistochemical results and imaging data of 866 patients (included 73 DCIS, 72 DCIS-Mi, and 721 IDC).
Patients with DCIS and DCIS-Mi were younger than those with IDC (P = 0.007). DCIS and DCIS-Mi often happened in premenopausal women while IDC was opposite (P <0.001). The incidence of IDC with node-positive was significantly higher than it in DCIS and DCIS-Mi (P <0.001). We also observed that the Her2-positive was more often found in patients with pure DCIS compared to those with DCIS-Mi and DCIS-I (P <0.001). There was a significant difference between the four subgroups (Luminal-A, Luminal-B, ERBB2+, Basal-like) from DCIS, DCIS-Mi, and IDC (P <0.001). Basal-like patients were fewer than other subgroups in DCIS, DCIS-Mi, and IDC. The incidence of the first performance of ultrasound (catheter winded and nodular mass) and mammography (nodular mass) had significantly difference among patients with DCIS, DCIS-Mi, and IDC (P <0.001).
Different clinicopathological, immunohistochemical, and imaging features among DCIS, DCIS-Mi, and IDC indicate that they are distinct entities. A larger sample size is needed for further study.
Breast neoplasms; Ductal carcinoma in situ; Ductal carcinoma in situ with microinvasion; Invasion breast cancer
Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently, no reliable biomarkers are available to predict the onset or progression of cGVHD. Therefore, in this study, we collected peripheral blood mononuclear cells from four patients with cGVHD and four ones with non-GVHD after hematopoietic stem cell transplantation and employed Affymetrix GeneChip Human U133 Plus 2.0 microarrays to screen the genes differentially expressed in cGVHD versus non-GVHD groups, with the aim to identify potential clinical biomarkers to predict cGVHD risk or progression. Microarray analysis demonstrated that the expression of 3180 genes changed significantly in cGVHD versus non-GVHD, with 879 genes upregulated and 2301 genes downregulated. Among them we chose CD28 and PI3K as candidates for further verification. Flow cytometry and quantitative real-time polymerase chain reaction analysis confirmed the significant upregulation of CD28 and PI3K in samples from patients with cGVHD compared with patients with non-GVHD, respectively. In conclusion, our study suggested that the upregulation of CD28 and PI3K contributed to the onset and progression of cGVHD and provided evidence that CD28 and PI3K may serve as promising biomarkers for cGVHD.
We first report here the genome sequences of 4 rearranged porcine circovirus type 2 strains, JSTZ, ZJQDH1, ZJQDH2, and JSHM, isolated from porcine sera in China. The complete circular genomes of these isolates are 578, 483, 574, and 772 nucleotides in length, respectively. They are predicted to be defective interfering particles of porcine circovirus type 2. The findings will help us to understand molecular evolution of porcine circovirus type 2 and the relationship between porcine circovirus type 2 and diseases.