In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).
We propose a novel physical mechanism for breaking the diffraction barrier in the far field. Termed fluorescence emission difference microscopy (FED), our approach is based on the intensity difference between two differently acquired images. When fluorescence saturation is applied, the resolving ability of FED can be further enhanced. A detailed theoretical analysis and a series of simulation tests are performed. The validity of FED in practical use is demonstrated by experiments on fluorescent nanoparticles and biological cells in which a spatial resolution of <λ/4 is achieved. Featuring the potential to realize a high imaging speed, this approach may be widely applied in nanoscale investigations.
Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare aggressive form of NK-cell neoplasm. We report an uncommon case of 36-year-old male who showed jaundice and spontaneous splenic rupture. The diagnosis was established by the biopsy of liver and spleen. The monomorphous medium-size neoplastic cells infiltrated into portal areas and sinus of liver as well as the cords and sinus of the spleen. Necrosis, mitotic figures and significant apoptosis could be seen easily. These neoplastic cells demonstrated a typical immunophenotype of CD3ε+, CD56+, CD16+, Granzyme B+, TIA-1+. T-cell receptor γ (TCR-γ) gene rearrangement analysis showed germline configuration and the result of in situ hybridization for Epstein-Barr virus-encoded RNA (EBER-ISH) was positive. The patient has undergone an aggressive clinical course and died of multi-organ function failure 14 days later after admission. To the best of our knowledge, this is the first case of ANKL with spontaneous splenic rupture, and we should pay more attention to recognize it.
The virtual slide(s) for this article can be found here:
Aggressive natural killer-cell leukemia; Jaundice; Spontaneous splenic rupture
To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves’ disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in CD19+ B cells and CD8+ T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (Pcombined = 2.27×10−12 and 7.11×10−13, respectively). Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs.
Buprenorphine/naloxone (BUP/NX) is not licensed for use in China or Thailand and there was little clinical experience with this drug combination in these countries at the inception of HIV Prevention Trial Network (HPTN) 058, a randomized trial comparing risk reduction counseling combined with either short-term or long-term medication assisted treatment with BUP/NX to prevent HIV infection and death among opioid-dependent injectors.
We conducted a safety phase that included the first 50 subjects enrolled at each of the three initial study sites (N=150). Clinical and laboratory assessments were conducted at baseline and weekly for the first 4 weeks. Changes in laboratory parameters were estimated with random effects models.
BUP/NX was well tolerated by study subjects and opioid withdrawal scores decreased substantially during the 3-day induction. Two participants experienced grade 3 clinical adverse events, which were categorized as probably not related to the study drug. Grade 2 or 3 increases in alanine aminotransferase (ALT) occurred in 25 (17%) subjects. The magnitude of ALT increase over 4-week follow-up was strongly associated with baseline ALT elevation.
In Chinese and Thai opioid-dependent injectors, we found BUP/NX to be effective in reducing opioid withdrawal symptoms and safe during short-term use. ALT increases were observed over 4-week-follow-up, which are consistent with reports from Western populations. Long-term safety and efficacy evaluations are indicated.
buprenorphine/naloxone; injection drug use; opioid dependence; HIV prevention; risk reduction counseling; safety; hepatic toxicity
Rationale and Objectives
Bilateral mammographic density asymmetry is a promising indicator in assessing risk of having or developing breast cancer. This study aims to assess the performance improvement of a computer-aided detection (CAD) scheme in detecting masses by incorporating bilateral mammographic density asymmetrical information.
Materials and Methods
A testing dataset containing 2400 full-field digital mammograms (FFDM) acquired from 600 examination cases was established. Among them, 300 are positive cases with verified cancer associated with malignant masses and 300 are negative cases. Two computerized schemes were applied to process images of each case. The first single-image based CAD scheme detected suspicious mass regions and the second scheme computed average and difference of mammographic tissue density depicted between the left and right breast. A fusion method based on rotation of the CAD scoring projection reference axis was then applied to combine CAD-generated mass detection scores and either the computed average or difference (asymmetry) of bilateral mammographic density scores. The CAD performance levels with and without incorporating mammographic density information were evaluated and compared using a free-response receiver operating characteristic (FROC) type data analysis method.
CAD achieved a case-based mass detection sensitivity of 0.74 and a region-based sensitivity of 0.56 at a false-positive rate of 0.25 per image. By fusing the CAD and bilateral mammographic density asymmetry scores, the case-based and region-based sensitivity levels of the CAD scheme were increased to 0.84 and 0.69, respectively, at the same false-positive rate. Fusion with average mammographic density only slightly increased CAD sensitivity to 0.75 (case-based) and 0.57 (region-based).
This study indicated that (1) bilateral mammographic density asymmetry was a stronger indicator of the case depicting suspicious masses than the average density computed from two breasts and (2) fusion between the conventional CAD scores and bilateral mammographic density asymmetry information could substantially increase CAD performance in mass detection.
Breast cancer; computer-aided detection of mammograms; mammographic density
The luteinizing hormone receptor (LHR) is a member of a subfamily of G protein-coupled receptors that is characterized by its alternative splicing. In a previous study, we identified a splice site mutation of intron 6 (IVS6-3C>A) in a patient suffering from Leydig cell hypoplasia, which leads to aberrant splicing of LHR mRNA. In vitro expression analysis confirmed that this mutation results in the skipping of exon 7 in the mature mRNA of the LHR gene. In this study, we determined the impact of IVS6-3C>A on the RNA secondary structure and function of LHR-Del7. The three-dimensional structure of the leucine-rich repeats in LHR was predicted by molecular modeling. Radioactive ligand-binding assays verified that LHR-Del7 has no binding affinity for hCG. Furthermore, we detected negligible cAMP production in cells transfected with LHR-Del7. Cells co-expressing LHR-WT and LHR-Del7 were able to generate cAMP in response to hCG, but there was no significant difference between cells transfected with LHR-WT/vector and LHR-WT/LHR-Del7, although the variant was able to localize to cell surface, similar to wild-type receptor. These results indicated that LHR-Del7 does not have a dominant negative effect on LHR-WT cell surface expression, and although the pathological splicing variant LHR-Del7 was able to localize to cell membranes it failed to bind hCG and had no effect on wild-type LHR.
function study; splicing variant; LHR
In silico screening of metazoan genome data identified multiple endogenous hepadnaviral elements in the budgerigar (Melopsittacus undulatus) genome, most notably two elements comprising about 1.3× and 1.0× the full-length genome. Phylogenetic and molecular dating analyses show that endogenous budgerigar hepatitis B viruses (eBHBV) share an ancestor with extant avihepadnaviruses and infiltrated the budgerigar genome millions of years ago. Identification of full-length genomes with preserved key features like ε signals could enable resurrection of ancient BHBV.
RNA interference (RNAi) has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC) therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment.
Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1) was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA) were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3) and non-HCC cell lines (L-02, Hela and SW1116) were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5) was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC) to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo.
The AFP-miRNA system could silence target gene (Beclin 1) but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1) in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo.
An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA) was successfully established. The system provides a usable tool for HCC-specific RNAi therapy, which may serve as a new treatment modality for HCC.
While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation.
To characterize the microcirculatory events that follow mast cell degranulation.
Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine.
Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.
Integrins mediate cell-cell and cell-extracellular matrix attachments. Integrins are signaling receptors because their cytoplasmic tails are docking sites for cytoskeletal and signaling proteins. Kindlins are a family of band 4.1-ezrin-radixin-moesin-containing intracellular proteins. Apart from regulating integrin ligand-binding affinity, recent evidence suggests that kindlins are involved in integrin outside-in signaling. Kindlin-3 is expressed in platelets, hematopoietic cells and endothelial cells. In humans, loss of kindlin-3 expression accounts for the rare autosomal disease leukocyte adhesion deficiency (LAD) type III that is characterized by bleeding disorders and defective recruitment of leukocytes into sites of infection. Studies have shown that the loss of kindlin-3 expression leads to poor ligand-binding properties of β1, β2 and β3 integrin subfamilies. The leukocyte-restricted β2 integrin subfamily comprises four members, namely αLβ2, αMβ2, αXβ2 and αDβ2. Integrin αMβ2 mediates leukocyte adhesion, phagocytosis, degranulation and it is involved in the maintenance of immune tolerance. Here we provide further evidence that kindlin-3 is required for integrin αMβ2-mediated cell adhesion and spreading using transfected K562 cells that expressed endogenous kindlin-3 but not β2 integrins. K562 stable cell line expressing si-RNA targeting kindlin-3, but not control-si-RNA, and transfected with constitutively activated integrin αMβ2N329S adhered and spread poorly on iC3b. We also show that kindlin-3 is required for the integrin αMβ2-Syk-Vav1 signaling axis that regulates Rac1 and Cdc42 activities. These findings reinforce a role for kindlin-3 in integrin outside-in signaling.
Hybridization and polyploidization may lead to divergence in adaptation and boost speciation in angiosperms and some lower animals. Epigenetic change plays a significant role in the formation and adaptation of polyploidy. Studies of the effects of methylation on genomic recombination and gene expression in allopolyploid plants have achieved good progress. However, relevant advances in polyploid animals have been relatively slower. In the present study, we used the bisexual, fertile, genetically stable allotetraploid generated by hybridization of Carassius auratus red var. and Cyprinus carpio L. to investigate cytosine methylation level using methylation-sensitive amplification polymorphism (MSAP) analysis. We observed 38.31% of the methylation changes in the allotetraploid compared with the parents at 355 randomly selected CCGG sites. In terms of methylation status, these results indicate that the level of methylation modification in the allotetraploid may have increased relative to that in the parents. We also found that the major methylation changes were hypermethylation on some genomic fragments and genes related to metabolism or cell cycle regulation. These results provide circumstantial evidence that DNA methylation might be related to the gene expression and phenotype variation in allotetraploid hybrids. Our study partly fulfils the need for epigenetic research in polyploid animals, and provides evidence for the epigenetic regulation of allopolyploids.
Left supraclavicular lymph node metastasis is a rare presentation of hepatocellular carcinoma (HCC). This phenomenon is easily neglected in the clinic. A 56-year-old man presented with HCC. On examination, a 1cm long left supraclavicular lymph node was palpated. Auxiliary examination indicated a lesion located in the right lobe of the liver. Fine needle aspiration cytology (FNAC) of the enlarged lymph node was performed; however, only necrosis was found. Hepatectomy was performed and HCC was confirmed by Hematoxylin-Eosin staining. However, 14 d after surgery, significantly enlarged left supraclavicular lymph nodes, a new intrahepatic lesion, and pulmonary and mediastinal metastasis appeared. An excisional biopsy of the left supraclavicular lymph node was performed, and its findings confirmed metastatic HCC. The patient’s HCC rapidly progressed and he died one month later. It is possible for HCC to metastasize to the left supraclavicular lymph node. Surgeons should always consider an overall physical examination. When left supraclavicular lymphadenopathy of unknown origin is encountered, FNAC should be performed initially. If the results are negative, an excisional biopsy and subsequent Positron emission tomography - computed tomography scanning should be performed. These are very important for making the correct diagnosis and for selecting reasonable therapies.
Left supraclavicular lymph node; Metastasis; Hepatocellular carcinoma; Fine needle aspiration cytology; Misdiagnosis
Bacterial transporter proteins are involved in the translocation of many essential nutrients and metabolites. However, many of these key bacterial transport systems remain to be identified, including those involved in the transport of riboflavin (vitamin B2). Pathogenic spirochetes lack riboflavin biosynthetic pathways, implying reliance on obtaining riboflavin from their hosts. Using structural and functional characterizations of possible ligand-binding components, we have identified an ABC-type riboflavin transport system within pathogenic spirochetes. The putative lipoprotein ligand-binding components of these systems from three different spirochetes were cloned, hyperexpressed in Escherichia coli, and purified to homogeneity. Solutions of all three of the purified recombinant proteins were bright yellow. UV-visible spectra demonstrated that these proteins were likely flavoproteins; electrospray ionization mass spectrometry and thin-layer chromatography confirmed that they contained riboflavin. A 1.3-Å crystal structure of the protein (TP0298) encoded by Treponema pallidum, the syphilis spirochete, demonstrated that the protein’s fold is similar to the ligand-binding components of ABC-type transporters. The structure also revealed other salient details of the riboflavin binding site. Comparative bioinformatics analyses of spirochetal genomes, coupled with experimental validation, facilitated the discovery of this new ABC-type riboflavin transport system(s). We denote the ligand-binding component as riboflavin uptake transporter A (RfuA). Taken together, it appears that pathogenic spirochetes have evolved an ABC-type transport system (RfuABCD) for survival in their host environments, particularly that of the human host.
Syphilis remains a public health problem, but very little is known about the causative bacterium. This is because Treponema pallidum still cannot be cultured in the laboratory. Rather, T. pallidum must be cultivated in laboratory rabbits, a restriction that poses many insurmountable experimental obstacles. Approaches to learn more about the structure and function of T. pallidum’s cell envelope, which is both the physical and functional interface between T. pallidum and its human host, are severely limited. One approach for elucidating T. pallidum’s cell envelope has been to determine the three-dimensional structures of its membrane lipoproteins, molecules that serve many critical survival functions. Herein, we describe a previously unknown transport system that T. pallidum uses to import riboflavin, an essential nutrient for the organism’s survival. Moreover, we found that this transport system is present in other pathogenic spirochetes. This is the first description of this new type of bacterial riboflavin transport system.
Congenital myasthenic syndromes are a heterogeneous group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. We performed linkage analysis, whole-exome and whole-genome sequencing to determine the underlying defect in patients with an inherited limb-girdle pattern of myasthenic weakness. We identify ALG14 and ALG2 as novel genes in which mutations cause a congenital myasthenic syndrome. Through analogy with yeast, ALG14 is thought to form a multiglycosyltransferase complex with ALG13 and DPAGT1 that catalyses the first two committed steps of asparagine-linked protein glycosylation. We show that ALG14 is concentrated at the muscle motor endplates and small interfering RNA silencing of ALG14 results in reduced cell-surface expression of muscle acetylcholine receptor expressed in human embryonic kidney 293 cells. ALG2 is an alpha-1,3-mannosyltransferase that also catalyses early steps in the asparagine-linked glycosylation pathway. Mutations were identified in two kinships, with mutation ALG2p.Val68Gly found to severely reduce ALG2 expression both in patient muscle, and in cell cultures. Identification of DPAGT1, ALG14 and ALG2 mutations as a cause of congenital myasthenic syndrome underscores the importance of asparagine-linked protein glycosylation for proper functioning of the neuromuscular junction. These syndromes form part of the wider spectrum of congenital disorders of glycosylation caused by impaired asparagine-linked glycosylation. It is likely that further genes encoding components of this pathway will be associated with congenital myasthenic syndromes or impaired neuromuscular transmission as part of a more severe multisystem disorder. Our findings suggest that treatment with cholinesterase inhibitors may improve muscle function in many of the congenital disorders of glycosylation.
congenital myasthenic syndrome; ALG2; ALG14; mutation; N-linked glycosylation
Highly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART.
Three cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression.
3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6–28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province.
Virologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken.
Statins are widely used cholesterol-lowering agents that may have potential anti-tumor effect. Epidemiological studies on statin use and renal cell carcinoma (RCC) risk have been inconsistent.
We investigated the association between statin use and RCC risk in the Nurses’ Health Study and Health Professionals Follow-up Study. A total of 80,782 women and 37,869 men were followed for 14 and 16 years respectively. Regular statin use was assessed at baseline and updated biennially during follow-up. RCC diagnosis was confirmed by medical record review.
We identified 277 incident RCC cases (164 women and 113 men). Compared with no current use, the multivariate relative risks for current statin use were 0.68 (95% CI: 0.46, 1.00) in women and 1.17 (95% CI, 0.75, 1.82) in men. The results for ever versus never users of statins were similar. We found no dose-response relation with duration of statin use and RCC risk. On subgroup analyses, statin use was associated with a reduced RCC risk among women with no history of hypertension.
Statin use may be associated with a lower risk of RCC in women, although these results need to be further investigated.
carcinoma; renal cell; neoplasms; statin; prospective studies
We detected Bartonella quintana in 48.6% of captive rhesus macaques from an animal facility in Beijing, China. Prevalence of infection increased over the period of observation. Our findings suggest that macaques may serve as reservoir hosts for B. quintana and that Pedicinus obtusus lice might act as efficient vectors.
Bartonella quintana; rhesus macaques; reservoir host; lice; transmission; China; vector-borne infections; Bartonella
βKlotho is a regulator in multiple metabolic processes, while its role in cancer remains unclear. We found the expression of βKlotho was down-regulated in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues. Hepatoma cells also showed decreased expression of βKlotho compared with normal hepatocyte cells. Reintroduction of βKlotho into hepatoma cells inhibited their proliferation. The anti-proliferative effect of βKlotho might be linked with G1 to S phase arrest, which was mediated by Akt/GSK-3β/cyclin D1 signaling, since forced expression βKlotho reduced the phosphorylation level of Akt and GSK-3β and induced down-regulation of cyclin D1. Furthermore, βKlotho overexpression could inhibit tumorgenesis, while constitutively activated Akt could override the suppressive effects of βKlotho in vivo. These data suggest βKlotho suppresses tumor growth in hepatocellular carcinoma.
AIM: To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shock-induced lung and intestine injuries.
METHODS: Wistar male rats were randomly divided into four groups: control group (Group A, n = 15); septic shock group (Group B, n = 15); early fluid resuscitation-treated septic shock group (Group C, n = 15); and early fluid resuscitation and inhalation of 2% hydrogen-treated septic shock group (Group D, n = 15). The activity of hydroxyl radicals, myeloperoxidase (MPO), superoxide dismutase (SOD), diamine oxidase (DAO), and the concentration of malonaldehyde (MDA) in the lung and intestinal tissue were assessed according to the corresponding kits. Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine. The expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method. The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting.
RESULTS: Septic shock elicited a significant increase in the levels of MDA (10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO (6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues. These effects were not significantly decreased by Group C pretreatment, but were significantly reduced by Group D pretreatment (MDA: 4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein; MPO: 2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue). The activity of SOD (250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock, and was not significantly increased by Group C pretreatment, but was significantly enhanced by Group D pretreatment (331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein). Histological evidence of lung hemorrhage, neutrophil infiltration and overexpression of IL-6, IL-8, and TNF-α was observed in lung tissues, all of which were attenuated by Group C and further alleviated by Group D pretreatment. Septic shock also elicited a significant increase in the levels of MDA, MPO and DAO (6.54 ± 0.68 kU/L vs 4.32 ± 0.33 kU/L) in intestinal tissues, all of which were further increased by Group C, but significantly reduced by Group D pretreatment. Increased Chiu scoring and overexpression of IL-6, IL-8 and TNF-α were observed in intestinal tissues, all of which were attenuated by Group C and further attenuated by Group D pretreatment.
CONCLUSION: Combined early fluid resuscitation and hydrogen inhalation may protect the lung and intestine of the septic shock rats from the damage induced by oxidative stress and the inflammatory reaction.
Early fluid resuscitation; Inhalation of hydrogen gas; Septic shock; Lung; Intestine; Oxidative damage
The most common teaching method used in China is lecturing, but recently, efforts have been widely undertaken to promote the transition from teacher-centered to student-centered education. The patient-oriented problem-solving (POPS) system is an innovative teaching-learning method that permits students to work in small groups to solve clinical problems, promotes self-learning, encourages clinical reasoning and develops long-lasting memory. To our best knowledge, however, POPS has never been applied in teaching immunology in China. The aim of this study was to develop POPS in teaching immunology and assess students’ and teachers’ perception to POPS.
321 second-year medical students were divided into two groups: I and II. Group I, comprising 110 students, was taught by POPS, and 16 immunology teachers witnessed the whole teaching process. Group II including the remaining 211 students was taught through traditional lectures. The results of the pre- and post-test of both groups were compared. Group I students and teachers then completed a self-structured feedback questionnaire for analysis before a discussion meeting attended only by the teachers was held.
Significant improvement in the mean difference between the pre- and post-test scores of those in Groups I and II was seen, demonstrating the effectiveness of POPS teaching. Most students responded that POPS facilitates self-learning, helps them to understand topics and creates interest, and 88.12% of students favored POPS over simple lectures. Moreover, while they responded that POPS facilitated student learning better than lectures, teachers pointed out that limited teaching resources would make it difficult for wide POPS application in China.
While POPS can break up the monotony of dialectic lectures and serve as a better teaching method, it may not be feasible for the current educational environment in China. The main reason for this is the relative shortage of teaching resources such as space, library facilities and well-trained teachers.
Patient-oriented problem-solving; Medical education; Immunology; China
Current computer-aided detection (CAD) schemes for detecting mammographic masses have several limitations including high correlation with radiologists’ detection and cueing most subtle masses only on one view. To increase CAD sensitivity in cueing more subtle masses that are likely missed and/or overlooked by radiologists without increasing false-positive rates, we investigated a new case-dependent cueing method by combining the original CAD-generated detection scores with a computed bilateral mammographic density asymmetry index. Using the new method, we adaptively raise CAD-generated scores of regions detected on “high-risk” cases to cue more subtle mass regions and reduce CAD scores of regions detected on “low-risk” cases to discard more false-positive regions. A testing dataset involving 78 positive and 338 negative cases was used to test this adaptive cueing method. Each positive case involves two sequential examinations in which the mass was detected in “current” examination and missed in “prior” examination but detected in a retrospective review by radiologists. Applying to this dataset, a pre-optimized CAD scheme yielded 75% case-based and 55% region-based sensitivity on “current” examinations at a false-positive rate of 0.25 per image. CAD sensitivity was reduced to 42% (case-based) and 27% (region-based) on “prior” examinations. Using the new cueing method, case-based and region-based sensitivity could maximally increase 9% and 33% on the “prior” examinations, respectively. The percentages of the masses cued on two views also increased from 27% to 65%. The study demonstrated that using this adaptive cueing method enabled to help CAD cue more subtle cancers without increasing false-positive cueing rate.
Computer-aided detection (CAD); Digital mammography; Bilateral mammographic density asymmetry; Mass detection
It has been well known that smoking alters the property and functionality of a wide range of immune cells including dendritic cells (DCs). However, a great deal of effort in the past has been mainly devoted to dissect the effect of smoking on pulmonary DCs, while its exact impact on circulating DCs remains to be fully addressed. Therefore, in the present report we particularly examined the impact of smoking on the number and subset of DCs in the peripheral blood by multi-parametric flow cytometry analysis. A significant increase for peripheral blood mononuclear cells (PBMCs) was noted in the smoking subjects. Subsequent studies revealed that the percentage for plasmacytoid DCs (pDCs) and total DCs in PBMCs was significantly higher in the smoking subjects as compared with that of control subjects, while the percentage for myeloid DCs (mDCs) did not differ between two groups. It was also found that the absolute number for total DCs, mDCs and pDCs were significantly higher in the smoking subjects than that of control subject. However, the mDC/pDC ratio was significantly reduced, suggesting that smoking impairs the balance of DC subsets. Given that pDCs are in favor of tolerogenic function, our data support that smoking could induce the production of pDCs to manifest immunosuppressive properties in the chronic smokers.
Smoking; dendritic cells; plasmacytoid dendritic cells; myeloid dendritic cells
The Macleaya spp., including Macleaya cordata and Macleaya microcarpa, are traditional anti-virus, inflammation eliminating, and insecticide herb medicines for their isoquinoline alkaloids. They are also known as the basis of the popular natural animal food addictive in Europe. However, few studies especially at genomics level were conducted on them. Hence, we performed the Macleaya spp. transcriptome and integrated it with iTRAQ proteome analysis in order to identify potential genes involved in alkaloids biosynthesis.
Methodology and Principal Findings
We elaborately designed the transcriptome, proteome and metabolism profiling for 10 samples of both species to explore their alkaloids biosynthesis. From the transcriptome data, we obtained 69367 and 78255 unigenes for M. cordata and M. microcarpa, in which about two thirds of them were similar to sequences in public databases. By metabolism profiling, reverse patterns for alkaloids sanguinarine, chelerythrine, protopine, and allocryptopine were observed in different organs of two species. We characterized the expressions of enzymes in alkaloid biosynthesis pathways. We also identified more than 1000 proteins from iTRAQ proteome data. Our results strongly suggest that the root maybe the organ for major alkaloids biosynthesis of Macleaya spp. Except for biosynthesis, the alkaloids storage and transport were also important for their accumulation. The ultrastructure of laticifers by SEM helps us to prove the alkaloids maybe accumulated in the mature roots.
To our knowledge this is the first study to elucidate the genetic makeup of Macleaya spp. This work provides clues to the identification of the potential modulate genes involved in alkaloids biosynthesis in Macleaya spp., and sheds light on researches for non-model medicinal plants by integrating different high-throughput technologies.