Photochemical switches represent a powerful method for improving pharmacological therapies and controlling cellular physiology. Here we report the photo-regulation of GABAA receptors (GABAARs) by a derivative of propofol (2,6-diisopropylphenol), a GABAAR allosteric modulator, that we have modified to contain photo-isomerizable azobenzene. Using α1β2γ2 GABAARs expressed in Xenopus laevis oocytes and native GABAARs of isolated retinal ganglion cells, we show that the trans-azobenzene isomer of the new compound (trans-MPC088), generated by visible light (wavelengths ~440 nm), potentiates the GABA-elicited response and at higher concentrations directly activates the receptors. cis-MPC088, generated from trans-MPC088 by UV light (~365 nm), produces little if any receptor potentiation/activation. In cerebellar slices, MPC088 co-applied with GABA affords bidirectional photo-modulation of Purkinje cell membrane current and spike-firing rate. The findings demonstrate photo-control of GABAARs by an allosteric ligand and open new avenues for fundamental and clinically oriented research on GABAARs, a major class of neurotransmitter receptors in the central nervous system.
Operations of cubic soft sets including “AND” operation and “OR” operation based on P-orders and R-orders are introduced and some related properties are investigated. An example is presented to show that the R-union of two internal cubic soft sets might not be internal. A sufficient condition is provided, which ensure that the R-union of two internal cubic soft sets is also internal. Moreover, some properties of cubic soft subalgebras of BCK/BCI-algebras based on a given parameter are discussed.
The novel H7N9 virus causes severe illness, including pneumonia and acute respiratory distress syndrome, with high rates of mortality. We investigated the association of initial radiologic characteristics obtained at admission with clinical outcomes in patients with avian influenza H7N9 pneumonia.
Demographics, comorbidities, clinical findings, radiologic appearance and scores of the affected lung parenchyma were compared between survivor group (n = 15) and mortality group (n = 7). Two radiologic scores were calculated, one using chest radiography and one using CT. Follow-up CT scans at discharge were analyzed in 12 patients of the survival group.
All the patients in mortality group developed acute respiratory distress syndrome and required mechanical ventilation, while in the survival group 33% (5/15) developed acute respiratory distress syndrome (P<0.05) and 27% (4/15) required mechanical ventilation (P<0.05). The mean radiographic and CT scores of the mortality group were 50% higher compared to the survival group (P<0.05). ROC analysis revealed an area under curve of 0.738 for the radiographic score with an optimal cutoff value of a score of 19 for prediction of mortality, with a sensitivity of 71% and a specificity of 67%, and an area under curve of 0.833 for the CT score with an optimal cutoff value of a CT score of 21 for prediction of mortality, with a sensitivity of 86% and a specificity of 73%. The mean CT score of the affected lung parenchyma at discharge was 30% lower than the initial CT examination (P<0.05).
High initial radiologic score is associated with mortality in patients with avian influenza H7N9 pneumonia.
Pituitary tumor transforming gene (PTTG) is an important paracrine growth factor involved in early lactotrope transformation and early onset of angiogenesis in pituitary hyperplasia. Emerging evidences have shown that PTTG expression may contribute to the etiology of pituitary adenomas; but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the correlations of PTTG expression with human pituitary adenomas.
A range of electronic databases were searched: MEDLINE (1966∼2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013) and the Chinese Biomedical Database (CBM) (1982∼2013) without language restrictions. Meta-analysis was performed using the STATA 12.0 software. Crude odds ratio (OR) or standard mean difference (SMD) with its corresponding 95% confidence interval (95%CI) were calculated.
Twenty-four clinical cohort studies were included with a total of 1,464 pituitary adenomas patients. The meta-analysis results revealed that patients with invasive pituitary adenomas had higher positive expression of PTTG than those of non-invasive patients (OR = 6.68, 95%CI = 3.72–11.99, P<0.001). We also found a significant difference in microvessel density between invasive and non-invasive patients (SMD = 1.81, 95%CI = 0.39–3.23, P = 0.013). However, there were no significant difference in PTTG expression between functional and non-functional patients with pituitary adenomas (OR = 1.11, 95%CI = 0.58–2.10, P = 0.753). No publication bias was detected in this meta-analysis (all P>0.05).
This present meta-analysis suggests that PTTG expression may be associated with tumor invasiveness and microvessel density of pituitary adenomas, while no correlations with functional status was found.
Deletion of fibroblast growth factor receptor 3 (Fgfr3) leads to hearing impairment in mice due to defects in the development of the organ of Corti, the sensory epithelium of the Cochlea. To examine the role of FGFR3 in auditory development, cochleae from Fgfr3−/− mice were examined using anatomical and physiological methods. Deletion of Fgfr3 leads to the absence of inner pillar cells and an increase in other cell types, suggesting that FGFR3 regulates cell fate. Defects in outer hair cell differentiation were also observed and probably represent the primary basis for hearing loss. Furthermore, innervation defects were detected consistent with changes in the fiber guidance properties of pillar cells. To elucidate the mechanisms underlying the effects of FGFR3, we examined the expression of Bmp4, a known target. Bmp4 was increased in Fgfr3−/− cochleae, and exogenous application of bone morphogenetic protein 4 (BMP4) onto cochlear explants induced a significant increase in the outer hair cells, suggesting the Fgf and Bmp signaling act in concert to pattern the cochlea.
hair cell; cochlea; BMP4; Prox1; innervation; Deiters’ cells; Pillar cells; microtubules; stria vascularis
The notion of fuzzy soft sets is a hybrid soft computing model that integrates both gradualness and parameterization methods in harmony to deal with uncertainty. The decomposition of fuzzy soft sets is of great importance in both theory and practical applications with regard to decision making under uncertainty. This study aims to explore decomposition of fuzzy soft sets with finite value spaces. Scalar
uni-product and int-product operations of fuzzy soft sets are introduced and some related properties are investigated. Using t-level soft sets, we define level equivalent relations and show that the quotient structure of the unit interval induced by level equivalent relations is isomorphic to the lattice consisting of all t-level soft sets of a given fuzzy soft set. We also introduce the concepts of crucial threshold values and complete threshold sets. Finally, some decomposition theorems for fuzzy soft sets with finite value spaces are established, illustrated by an example concerning the classification and rating of multimedia cell phones. The obtained results extend some classical decomposition theorems of fuzzy sets, since every fuzzy set can be viewed as a fuzzy soft set with a single parameter.
Purpose: Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of αvβ3-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed 68Ga-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)]2 (68Ga-PRGD2) to evaluate the αvβ3-integrin-related repair in post-MI and post-stroke patients via positron emission tomography/computed tomography (PET/CT).
Methods: With Institutional Review Board approval, 23 MI patients (3 days-2 years post-MI) and 16 stroke patients (3 days-13 years post-stroke) were recruited. After giving informed consent, each patient underwent a cardiac or brain PET/CT scan 30 min after the intravenous injection of 68Ga-PRGD2 in a dose of approximately 1.85 MBq (0.05 mCi) per kilogram body weight. Two stroke patients underwent repeat scans three months after the event.
Results: Patchy 68Ga-PRGD2 uptake occurred in or around the ischemic regions in 20/23 MI patients and punctate multifocal uptake occurred in 8/16 stroke patients. The peak standardized uptake values (pSUVs) in MI were 1.94 ± 0.48 (mean ± SD; range, 0.62-2.69), significantly higher than those in stroke (mean ± SD, 0.46 ± 0.29; range, 0.15-0.93; P < 0.001). Higher 68Ga-PRGD2 uptake was observed in the patients 1-3 weeks after the initial onset of the MI/stroke event. The uptake levels were significantly correlated with the diameter of the diseases (r = 0.748, P = 0.001 for MI and r = 0.835, P = 0.003 for stroke). Smaller or older lesions displayed no uptake.
Conclusions: 68Ga-PRGD2 uptake was observed around the ischemic region in both MI and stroke patients, which was correlated with the disease phase and severity. The different image patterns and uptake levels in MI and stroke patients warrant further investigations.
68Ga-PRGD2; PET/CT; stroke; myocardial infarction; αvβ3-integrin; angiogenesis.
Parasite infections often result in a switch of the human body’s predominant immune reaction from T-helper 1 (Th1)-type to Th2-type. Hence, parasite infections are widely expected to accelerate the progression of human immunodeficiency virus (HIV) infections to acquired immunodeficiency syndrome (AIDS). In the People’s Republic of China, both parasitic diseases and AIDS are epidemic in certain rural areas, and co-infections are relatively common. However, no population-based studies have yet investigated the frequency of HIV and parasite co-infections, and its effects on immune responses. We studied (1) the immune status of an HIV-infected population, and (2) the effect of co-infection of HIV and intestinal parasites on selected parameters of the human immune system.
A total of 309 HIV-infected individuals were recruited and compared to an age-matched and sex-matched control group of 315 local HIV-negative individuals. Questionnaires were administered to all participants to obtain information on sociodemographic characteristics, sanitation habits, family income, and recent clinical manifestations. Two consecutive stool samples and 10 ml samples of venous blood were also collected from each individual for the diagnosis of parasite infections and quantitative measurements of selected cytokines and CD4+ T-lymphocytes, respectively.
During the study period, 79 HIV-infected individuals were not under highly active antiretroviral therapy (HAART) and were thus included in our analysis; the prevalence of intestinal helminth infections was 6.3% and that of protozoa was 22.8%. The most common protozoan infections were Blastocystis hominis (B. hominis) (13.9%) and Cryptosporidium spp. (10.1%). The prevalence of Cryptosporidium spp. in HIV-infected individuals was significantly higher than that in HIV negative individuals (P < 0.05). Compared to the non-co-infected population, no significant difference was found for any of the measured immunological indicators (P > 0.05). However, the following trends were observed: IFN-γ levels were lower, but the IL-4 level was higher, in the population co-infected with HIV and helminths. In the population co-infected with HIV and B. hominis, the IL-2 level was higher. The population co-infected with HIV and Cryptosporidium spp. had markedly lower CD4+ T-lymphocyte counts.
According to the immunologic profile, co-infection with helminths is disadvantageous to HIV-infected individuals. It was associated with a shift in the Th1/Th2 balance in the same direction as that caused by the virus itself, which might indicate an acceleration of the progress from an HIV infection to AIDS. Co-infection with Cryptosporidium spp. was not associated with a significant change in immune factors but co-infection with Cryptosporidium spp. was associated with a reduced level of CD4 + T-lymphocytes, confirming the opportunistic nature of such infections. Co-infection with B. hominis, on the other hand, was associated with an antagonistic shift in the immunological profile compared to an HIV infection.
HIV; Intestinal parasite; Co-infection; Immunological profile; People’s Republic of China
We investigated the prevalence of and risk factors for small airway obstruction (SAO) among Chinese island residents to establish means to prevent and treat SAO.
From October 17, 2011 to November 1, 2011, a total of 2,873 residents aged >20 years who lived on the Huangqi Peninsula of Fujian were recruited by random cluster sampling. They were asked to complete a Burden of Obstructive Lung Disease (BOLD) questionnaire and underwent physical examinations and lung function evaluations. SAO was defined as a forced expiratory flow at 50% of vital capacity, Vmax50%, of less than 70% of predicted. Risk factors for SAO were assessed from among demographic and anthropometric variables, blood chemistry results, and questionnaire response items.
A total of 216 (7.52%) Chinese island residents were identified as having SAO (95 males; 121 females). Their survey and test results were compared with 432 age and sex-matched healthy controls (192 males; 240 females) for SAO risk factors. Among numerous factors investigated, only diabetes mellitus (p = 0.039), smoking index (SI, p<0.001 for SI>600), second hand smoke (p = 0.002), and lack of regular exercise (p<0.001) were significant risk factors for SAO.
The risk factors for SAO among Chinese island residents appeared to be similar to those among people who live in high-density urban environments and impoverished rural areas. Public health policies and medical practices directed toward improving respiratory health for island residents should be comparable to those used for urban and rural dwellers.
To investigate the effects of Msx2 on lens epithelium cell cycle, and evaluate the changes of the proliferation, apoptosis of lens epithelium cells.
Mice lens epithelium cells were cultured and transfected with pEGFP-Msx2 and control. Msx2-deﬁcient mice (Msx2−/−) lens tissue were isolated. Lens tissue and transfected cells were prepared for mRNA extraction using Trizol reagent. CyclinD1 and Prox1 expression were evaluated by real-time RT-PCR. BrdU incorporation and apoptosis rate were investigated by immunofluorescence and flow cytometry analysis.
After transfected with pEGFP-Msx2, lens epithelium cells failed to incorporate BrdU and anti-phospho-histone-3 immunofluorescence failed to detect cell nuclei which GFP were positive. Msx2 over expression resulted in increasing apoptosis rate in lens epithelium cells. CyclinD1 and Prox1 expression increased significantly in Msx2 knockout mice by real-time RT-PCR quantization and CyclinD1 expression decreased significantly in Msx2 overexpressed cell.
Msx2 has the effect of inhibiting proliferation and differentiation, triggering apoptosis on mice lens epithelium cells.
Msx2; lens epithelium cell; cell cycle
The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio) and cervical stromal involvement in patients with endometrioid adenocarcinoma.
We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement.
The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively). Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively). At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific.
Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement.
neutrophil-lymphocyte ratio; platelet-lymphocyte ratio; endometrioid adenocarcinoma; cervical stromal involvement
The GABAC receptor, a postsynaptic membrane receptor expressed prominently in the retina, is a ligand-gated ion channel that consists of a combination of ρ subunits. We report characterization of a novel guinea pig polyclonal antibody, termed GABAC Ab N-14, directed against a 14-mer peptide (N-14) of the extracellular domain of the human ρ1 subunit. The antibody exhibits high sensitivity for N-14 by ELISA. In Western blots, GABAC Ab N-14 shows reactivity with the ρ1 subunit of preparations obtained from ρ1 GABAC-expressing neuroblastoma cells, Xenopus oocytes, and mammalian retina and brain. Flow cytometry reveals a rightward shift in mean fluorescence intensity of GABAC-expressing neuroblastoma cells probed with GABAC Ab N-14. Immunostaining of neuroblastoma cells and oocytes with GABAC Ab N-14 yields fluorescence only with GABAC-expressing cells. Antibody binding has no effect on GABA-elicited membrane current responses. Immunostaining of human retinal sections shows preferential staining within the inner plexiform layer. GABAC Ab N-14 appears well suited for investigative studies of GABAC ρ1 subunit in retina and other neural tissues.
GABA receptor; GABAC; retina; ρ1 subunit; antibody
To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma (DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen (R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P = 0.001), Bcl-6-negative patients (P = 0.01), and MUM-1-positive patients (P = 0.003). The risk of disease relapse in patients with non-GCB subtype (P = 0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P = 0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P = 0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.
Diffuse large B-cell lymphoma; rituximab; chemotherapy; NF-κB; immunohistochemistry
The title mononuclear complex, [Ni(C7H3NO4)(C9H10N2)3], shows a central NiII atom which is coordinated by two carboxylate O atoms and the N atom from a pyridine-2,6-dicarboxylate ligand and by three N atoms from different 5,6-dimethyl-1H-benzimidazole ligands in a distorted octahedral geometry. The crystal structure shows intermolecular N—H⋯O hydrogen bonds.
In the title complex, [Ni(C7H3NO4)(C7H6N2)3], the NiII ion is coordinated by two carboxylate O atoms and the N atom from a pyridine-2,6-dicarboxylate ligand and by three N atoms from three benzimidazole ligands to form a slightly distorted octahedral geometry. In the crystal, molecules are linked by N—H⋯O hydrogen bonds to form a three-dimensional network.
Homonymous quadrantanopsia results from retrochiasmal lesions in the visual pathway. Invasive mole is a benign tumor that arises from myometrial invasion of a hydatidiform mole via direct extension through tissue or venous channels. Cerebral metastasis of invasive mole is rare and there has been no report demonstrating homonymous quadrantanopsia as the first manifestation of metastasis in any trophoblastic neoplasms.
We report the case of a 31-year-old Asian woman who presented with right homonymous inferior quadrantanopsia from the mass effect of a solitary cerebral metastasis from an invasive mole. A magnetic resonance image (MRI) of the brain showed a metastatic tumor in the left occipital lobe. The visual field improved slightly after chemotherapy. There was a reduction in the tumor size and the surrounding edema. This is the first case report demonstrating that homonymous quadrantanopsia should be included in the manifestations of the metastasis of an invasive mole.
The presentation of homonymous quadrantanopsia must alert ophthalmologists to conduct a complete medical history and arrange specialist consultation.
Cerebral metastasis; Homonymous Quadrantanopsia; Invasive mole
Motivation: Immunoassays are primary diagnostic and research tools throughout the medical and life sciences. The common approach to the processing of immunoassay data involves estimation of the calibration curve followed by inversion of the calibration function to read off the concentration estimates. This approach, however, does not lend itself easily to acceptable estimation of confidence limits on the estimated concentrations. Such estimates must account for uncertainty in the calibration curve as well as uncertainty in the target measurement. Even point estimates can be problematic: because of the non-linearity of calibration curves and error heteroscedasticity, the neglect of components of measurement error can produce significant bias.
Methods: We have developed a Bayesian approach for the estimation of concentrations from immunoassay data that treats the propagation of measurement error appropriately. The method uses Markov Chain Monte Carlo (MCMC) to approximate the posterior distribution of the target concentrations and numerically compute the relevant summary statistics. Software implementing the method is freely available for public use.
Results: The new method was tested on both simulated and experimental datasets with different measurement error models. The method outperformed the common inverse method on samples with large measurement errors. Even in cases with extreme measurements where the common inverse method failed, our approach always generated reasonable estimates for the target concentrations.
Availability: Project name: Baecs; Project home page: www.computationalimmunology.org/utilities/; Operating systems: Linux, MacOS X and Windows; Programming language: C++; License: Free for Academic Use.
Supplementary data are available at Bioinformatics online.
Intestinal parasite infections (IPIs) are among the most significant causes of illness and disease of socially and economically disadvantaged populations in developing countries, including rural areas of the People's Republic of China. With the spread of the human immunodeficiency virus (HIV) among rural Chinese populations, there is ample scope for co-infections and there have been increasing fears about their effects. However, hardly any relevant epidemiological studies have been carried out in the country. The aim of the present survey was to assess the IPI infection status among a representative sample of HIV-positive Chinese in rural Anhui province, and compare the findings with those from a cohort of non-infected individuals.
A case control study was carried out in a rural village of Fuyang, Anhui province, China. Stool samples of all participants were examined for the presence of intestinal parasites. Blood examination was performed for the HIV infection detection and anemia test. A questionnaire was administered to all study participants.
A total of 302 HIV positive and 303 HIV negative individuals provided one stool sample for examination. The overall IPI prevalence of intestinal helminth infections among HIV positives was 4.3% (13/302) while it was 5.6% (17/303) among HIV negatives, a non-significant difference. The prevalence of protozoa infections among HIV positives was 23.2% while the rate was 25.8% among HIV negatives. The species-specific prevalences among HIV positives were as follows: 3.6% for hookworm, 0.7% for Trichuris trichiura, zero for Ascaris lumbricoides, 0.3% for Clonorchis sinensis, 1.3% for Giardia intestinalis, 16.2% for Blastocystis hominis, 1.7% for Entamoeba spp. and 8.3% for Cryptosporidium spp.. Cryptosporidium spp. infections were significantly more prevalent among HIV positives (8.3%) compared to the HIV negative group (3.0%; P < 0.05). Among people infected with HIV, Cryptosporidium spp. was significantly more prevalent among males (12.6%) than females (4.4%; P < 0.05). According to multivariate logistic regression, the factors significantly associated with parasite infections of the people who were HIV positive included sex (male: OR = 6.70, 95% CI: 2.030, 22.114), younger age (less than 42 years old: OR = 4.148, 95% CI: 1.348, 12.761), and poor personal hygiene habits (OR = 0.324, 95% CI: 0.105, 0.994).
HIV positive individuals are more susceptible to co-infections with Cryptosporidium spp. than HIV negative people, particularly younger males with poor personal hygiene habits, indicating a need for targeted hygiene promotion, IPI surveillance and treatment.
HIV; Intestinal parasites; Helminths; Protozoa; Co-infection; China
Fatty acids and derivatives (FADs) are resources for natural antimicrobials. In order to screen for additional potent antimicrobial agents, the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay. Monoglycerides of fatty acids were the most potent class of fatty acids, among which monotridecanoin possessed the most potent antimicrobial activity. The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR: R
LOO=0.910; CoMFA: R
2=0.588, respectively). Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structure-activity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents.
Fatty acid derivatives; Quantitative structure-activity relationship; Comparative molecular field analysis; Antimicrobial activity
AIM: To compare and evaluate the appropriate prognostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection.
METHODS: A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer (UICC) N staging methods and the metastatic lymph node ratio (MLNR) staging. Homogeneity, discriminatory ability, and gradient monotonicity of the various staging methods were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. The area under the curve (AUC) was calculated to compare the predictive ability of the aforementioned three staging methods.
RESULTS: Optimal cut-points of the MLNR were calculated as MLNR0 (0), MLNR1 (0.01-0.30), MLNR2 (0.31-0.50), and MLNR3 (0.51-1.00). In univariate, multivariate, and stratified analyses, MLNR staging was superior to the 6th and 7th edition UICC N staging methods. MLNR staging had a higher AUC, higher linear trend and likelihood ratio χ2 scores and lower AIC values than the other two staging methods.
CONCLUSION: MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edition UICC N classifications and should be considered as an alternative to current pathological N staging.
Gastric cancer; Metastatic lymph node ratio; Prognosis
The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m2), leucovorin (20 mg/m2) bolus, and 5-fluorouracil intravenous infusion (500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.
Bevacizumab; chemotherapy; first-line treatment; Chinese patients; metastatic colorectal cancer
AIM: To identify and assess the novel makers for detection of Shiga toxin producing Escherichia coli (STEC) O157:H7 with an integrated computational and experimental approach.
METHODS: High-throughput NCBI blast (E-value cutoff e-5) was used to search homologous genes among all sequenced prokaryotic genomes of each gene encoded in each of the three strains of STEC O157:H7 with complete genomes, aiming to find unique genes in O157:H7 as its potential markers. To ensure that the identified markers from the three strains of STEC O157:H7 can serve as general markers for all the STEC O157:H7 strains, a genomic barcode approach was used to select the markers to minimize the possibility of choosing a marker gene as part of a transposable element. Effectiveness of the markers predicted was then validated by running polymerase chain reaction (PCR) on 18 strains of O157:H7 with 5 additional genomes used as negative controls.
RESULTS: The blast search identified 20, 16 and 20 genes, respectively, in the three sequenced strains of STEC O157:H7, which had no homologs in any of the other prokaryotic genomes. Three genes, wzy, Z0372 and Z0344, common to the three gene lists, were selected based on the genomic barcode approach. PCR showed an identification accuracy of 100% on the 18 tested strains and the 5 controls.
CONCLUSION: The three identified novel markers, wzy, Z0372 and Z0344, are highly promising for the detection of STEC O157:H7, in complementary to the known markers.
Shiga toxin producing Escherichia coli O157:H7; Diagnosis; Marker genes; Infectious diseases
ErbB2 protein is essential for the development of Schwann cells and for the normal fiber growth and myelin formation of peripheral nerves. We have investigated the fate of the otocyst-derived inner ear sensory neurons in the absence of ErbB2 using ErbB2 null mutants. Afferent innervation of the ear sensory epithelia shows numerous fibers overshooting the organ of Corti, followed by a reduction of those fibers in near term embryos. This suggests that mature Schwann cells do not play a role in targeting or maintaining the inner ear innervation. Comparable to the overshooting of nerve fibers, sensory neurons migrate beyond their normal locations into unusual positions in the modiolus. They may miss a stop signal provided by the Schwann cells that are absent as revealed with detailed histology. Reduction of overshooting afferents may be enhanced by a reduction of the neurotrophin Ntf3 transcript to about 25% of wild type. Ntf3 transcript reductions are comparable to an adult model that uses a dominant negative form of ErbB4 expressed in the supporting cells and Schwann cells of the organ of Corti. ErbB2 null mice retain afferents to inner hair cells possibly because of the prominent expression of the neurotrophin Bdnf in developing hair cells. Despite the normal presence of Bdnf transcript, afferent fibers are disoriented near the organ of Corti. Efferent fibers do not form an intraganglionic spiral bundle in the absence of spiral ganglia and appear reduced and disorganized. This suggests that either ErbB2 mediated alterations in sensory neurons or the absence of Schwann cells affects efferent fiber growth to the organ of Corti.
Ear development; Auditory sensory neuron; Neurotrophin; Pathfinding; Neuronal migration
Both genetic and epigenetic alterations can control the progression of cancer. Genetic alterations are impossible to reverse, while epigenetic alterations are reversible. This advantage suggests that epigenetic modifications should be preferred in therapy applications. DNA methyltransferases and histone deacetylases have become the primary targets for studies in epigenetic therapy. Some DNA methylation inhibitors and histone deacetylation inhibitors are approved by the US Food and Drug Administration as anti-cancer drugs. Therefore, the uses of epigenetic targets are believed to have great potential as a lasting favorable approach in treating breast cancer.
breast cancer; epigenetic therapy; DNA methylation inhibitors; Histone deacetylation inhibitors