We propose a new method for tumor classification from gene expression data, which mainly contains three steps. Firstly, the original DNA microarray gene expression data are modeled by independent component analysis (ICA). Secondly, the most discriminant eigenassays extracted by ICA are selected by the sequential floating forward selection technique. Finally, support vector machine is used to classify the modeling data. To show the validity of the proposed method, we applied it to classify three DNA microarray datasets involving various human normal and tumor tissue samples. The experimental results show that the method is efficient and feasible.
Artificial Intelligence ; Colonic Neoplasms ; classification ; genetics ; Computational Biology ; Data Interpretation, Statistical ; Databases, Genetic ; Discriminant Analysis ; Gene Expression Profiling ; statistics & numerical data ; Glioma ; classification ; genetics ; Humans ; Leukemia ; classification ; genetics ; Models, Statistical ; Neoplasms ; classification ; genetics ; Oligonucleotide Array Sequence Analysis ; statistics & numerical data ; Principal Component Analysis

Objective To investigate the diagnostic value of narrow?band imaging in patients with nonampullary duodenal superficial elevated lesions. Methods Analysis were limited to respondents diagnosed with nonampullary duodenal superficial elevated lesions on endoscopic examination. The lesion distribution, fusion, diameter, vascular and surface pattern were evaluated and compared with NBI mode according to pathological group. Results 72 cases were collected, 35 (48.61%) cases were inflammation, 17 (23.61%) cases were heterotopic gastric mucosa, 12 (16.67%) cases were gastric duodenal metaplasia and 8 (11.11%) cases were adenoma. Among the four types of duodenal lesion, solitary adenomatous lesions were observed more frequently and larger in diameter. Surface pattern of inflammatory lesions were consistent with the surrounding mucosa. Vascular pattern and fusion may be helpful to differential some superficial elevated lesions. Conclusion Nonampullary duodenal superficial elevated lesions can be identified preliminarily by NBI. Meanwhile, diagnosis accuracy and positive rate can be improved by target biopsy.

The disorders of DNA and histone methylation have a close relationship with the development and progression of tumors. Epigenetic regulation is critical in maintaining the stability and integrity of the expression profiles of different cell types by modifying DNA methylation and histone methylation. However, the abnormal changes of methylation often result in the development and progression of tumors. This review summarized the theory of tumor genomic and histone methylation, detection methods of methylation and their applications, and the clinical application of methylation as biological markers and drug targets.
DNA Methylation ; Histones ; metabolism ; Humans ; Methylation ; Neoplasms ; genetics ; metabolism

As the most homologic homologue of silent information regulator 2 of yeast, Sirt1 gene is extensively expressed in mature tissues, and is rich in early embryo and reproductive cells. It is involved in the regulation of gene transcription, energy metabolism and cell aging. It promotes fat mobilization in adipocytes and glucose production in liver and regulates insulin secretion in islet beta cell. Furthermore, Sirt1 gene is an essential endogenous apoptosis inhibitor. In future, it may be used as new drug targets or applied in other disease management modalities.
Animals ; Humans ; Sirtuin 1 ; genetics ; metabolism ; physiology

OBJECTIVETo investigate the role of activated brain regions in Parkinson's disease (PD) during tactile stimulation.

METHODSTwenty-one patients with early PD[mean age (60.43 +/-9.65)y] and twenty-two age-matched healthy controls [mean age (59.23 +/-11.12)y] were enrolled in the study. All the patients were tested by the United Parkinson Disease Rating Scale (UPDRS) as the evaluation of the disease severity. A block design was used when the finger tactile stimulation was given to the subjects. The hypoactive and hyperactive regions of PD patients were confirmed first, which were identified as regions of interest (ROI). ROI analysis was performed to quantify BOLD signal changes when subjects were under tactile stimulation. The correlations of signal changes with disease severity, and correlations of hyperactive with hypoactive regions were analyzed.

RESULTSRight primary sensory and motor cortex, right supplementary motor area (SMA), bilateral caudates, bilateral precuneus, bilateral occipital visual cortex and left middle temporal gyrus were hypoactivated in PD, while right prefrontal cortex (PFC) and right caudate were hyperactivated. The hypoactivation of right SMA was negatively correlated with disease severity. All the hypoactive and hyperactive regions were positively correlated with activation of caudates. There was a positive correlation between hyperactive PFC and hypoactive regions.

CONCLUSIONSThe signal change of SMA is directly related to disease severity in early PD, and caudates may play a significant role in PD tactile processing. The hyperactivation of PFC may be not a compensation but a pathophysiological change related to PD neural dysfunction.

Aged ; Brain ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mechanoreceptors ; physiology ; Middle Aged ; Parkinson Disease ; physiopathology ; Severity of Illness Index ; Time Factors ; Touch ; physiology ; Touch Perception ; physiology

OBJECTIVETo examine the age, sex, and hemispheric differences in volume of the striatum by MRI in healthy adults.

METHODSThe volumes of the bilateral caudate nucleus and putamen were measured on MR images in 100 healthy right-handed adults (18-70 y).

RESULTSThe volume of bilateral caudate nucleus and putamen in healthy adults was (8.42 +/-0.88) cm(3) and (8.90 +/-0.89) cm(3), which were decreased with aging (for caudate nucleus r=-0.727, P<0.001; for putamen r=-0.709, P<0.001). The average annual shrinkage rate was 0.52 % in the caudate nucleus and 0.50 % in the putamen. There were no gender differences in the volume of the striatum, however, the age-related shrinkage of the striatum was more evident in men than that in women. The volume of the left caudate nucleus (t=4.43, P<0.001) and the putamen (t=4.88, P<0.001) was greater than that of its right counterpart.

CONCLUSIONBilateral age-related shrinkage of the striatum is found in healthy adults, which is more evident in men than that in women. In both sexes, significant leftward asymmetry in volume of the caudate nucleus and the putamen is found.

Adolescent ; Adult ; Age Factors ; Aged ; China ; Corpus Striatum ; anatomy & histology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Reference Values ; Sex Factors ; Young Adult

OBJECTIVETo retrospectively analysis the treatment characteristics of the systemic situation in patients with crush syndrome after Wenchuan earthquake happened in May 12th, 2008.

METHODSForty-nine patients with crush syndrome and subsequent acute renal failure (ARF) due to the earthquake were treated in West China Hospital. All of patients had been rescued from buildings that collapsed in Wenchuan earthquake. The major associated injuries were in the low extremities and upper extremities. 49 patients developed ARF with increased concentrations of serum creatinine (mean 64 022 U/L) had underwent haemodialysis. Hyperkalaemia was seen in 9 patients and four of them underwent haemodialysis. 49 patients were administered hemodialysis.

RESULTSNo patient died. All patients who suffered from the ARF were weaned from hemodialysis after admitted 7 to 35 days. Forty-five extremities underwent amputations and 52 extremities had fasciotomy.

CONCLUSIONSCrush syndrome requires urgent recognition and prompt surgical treatment with simultaneous measures to control hyperkalemia and ARF. The authors believe that immediate intensive care therapy and multi-subjective coordination would have improved the survival rate.

Acute Kidney Injury ; etiology ; surgery ; therapy ; Adolescent ; Adult ; Aged ; Amputation ; Child ; Crush Syndrome ; etiology ; surgery ; therapy ; Decompression, Surgical ; Earthquakes ; Female ; Humans ; Male ; Middle Aged ; Renal Replacement Therapy ; Retrospective Studies ; Treatment Outcome ; Wounds and Injuries ; complications

OBJECTIVETo develop a specific SARS virus-targeted antibody preparation for emergent prophylaxis and treatment of SARS virus infection.

METHODSBy using phage display technology, we constructed a naive antibody library from convalescent SARS patient lymphocytes. To obtain the neutralizing antibody to SARS virus surface proteins, the library panning procedure was performed on purified SARS virions and the specific Fab antibody clones were enriched by four rounds of repeated panning procedure and screened by highthroughput selection. The selected Fab antibodies expressed in the periplasma of E. coli were soluble and further purified and tested for their binding properties and antiviral function to SARS virus. The functional Fab antibodies were converted to full human IgG antibodies with recombinant baculovirus/insect cell systems and their neutralizing activities were further determined.

RESULTSAfter four rounds of the panning, a number of SARS-CoV virus-targeted human recombinant Fab antibodies were isolated from the SARS patient antibody library. Most of these were identified to recognize both natural and recombinant SARS spike (S) proteins, two Fab antibodies were specific for the virus membrane (M) protein, only one bound to SARS-CoV nucleocapsid protein. The SARS-CoV S and M protein-targeted Fab or IgG antibodies showed significant neutralizing activities in cytopathic effect (CPE) inhibition neutralization test, these antibodies were able to completely neutralize the SARS virus and protect the Vero cells from CPE after virus infection. However, the N protein-targeted Fab or IgG antibodies failed to neutralize the virus. In addition, the SARS N protein-targeted human Fab antibody reacted with the denatured N proteins, whereas none of the S and M protein specific neutralizing antibodies did. These results suggested that the S and M protein-specific neutralizing antibodies could recognize conformational epitopes which might be involved in the binding of virions to cellular receptors and the fusion activity of the virus.

CONCLUSIONThe SARS-CoV spike protein and membrane proteins are able to elicite efficient neutralizing antibodies in SARS patients. The neutralizing antibodies we generated in this study may be more promising candidates for prophylaxis and treatment of SARS infection.

Amino Acid Sequence ; Animals ; Antibodies, Viral ; immunology ; Cercopithecus aethiops ; Humans ; Membrane Glycoproteins ; immunology ; Neutralization Tests ; Peptide Library ; Protein Binding ; Protein Engineering ; Recombinant Proteins ; immunology ; SARS Virus ; immunology ; Severe Acute Respiratory Syndrome ; immunology ; virology ; Spike Glycoprotein, Coronavirus ; Vero Cells ; Viral Envelope Proteins ; immunology ; Viral Matrix Proteins ; immunology

Applying poly(ADP-ribose) polymerase inhibitors (PARPi) to the treatment of cancers with homologous recombination deficiency (HRDness) has been a great advance in the field of molecular therapeutics. However, in the clinic patients lacking the specific mutations or developing reverse mutations in the process of PARPi treatment may not benefit from PARPi monotherapy. Therefore, targeting homologous recombination (HR) repair with molecularly targeted agents is becoming an attractive research focus and is raising the concept of "chemical HRDness". HR repair is an evolutionarily conserved and extensively regulated process that employs sister chromatids as the template to repair DNA double-strand breaks with high fidelity. In addition to directly targeting HR components, modulation of regulatory pathways controlling HR repair is effective in achieving the "HRDness" phenotype; this includes modulation of the cell cycle checkpoint regulatory pathway, the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the chromatin remodeling pathway, etc. Targeting HR repair can not only result in "synthetic lethality" when combined with PARPi, but also sensitizes cancers to traditional radio/chemotherapy and novel immunotherapy. In this review we describe the HR repair pathway and its regulatory pathways, summarize the preclinical and clinical outcomes of targeting HR repair, discuss the remaining problems in this field and provide a prospective on its application in tumor therapy.

BACKGROUND: Prenatal evaluation of fetal lung maturity (FLM) is a challenge, and an effective non-invasive method for prenatal assessment of FLM is needed. The study aimed to establish a normal fetal lung gestational age (GA) grading model based on deep learning (DL) algorithms, validate the effectiveness of the model, and explore the potential value of DL algorithms in assessing FLM. METHODS: A total of 7013 ultrasound images obtained from 1023 normal pregnancies between 20 and 41 + 6 weeks were analyzed in this study. There were no pregnancy-related complications that affected fetal lung development, and all infants were born without neonatal respiratory diseases. The images were divided into three classes based on the gestational week: class I: 20 to 29 + 6 weeks, class II: 30 to 36 + 6 weeks, and class III: 37 to 41 + 6 weeks. There were 3323, 2142, and 1548 images in each class, respectively. First, we performed a pre-processing algorithm to remove irrelevant information from each image. Then, a convolutional neural network was designed to identify different categories of fetal lung ultrasound images. Finally, we used ten-fold cross-validation to validate the performance of our model. This new machine learning algorithm automatically extracted and classified lung ultrasound image information related to GA. This was used to establish a grading model. The performance of the grading model was assessed using accuracy, sensitivity, specificity, and receiver operating characteristic curves. RESULTS: A normal fetal lung GA grading model was established and validated. The sensitivity of each class in the independent test set was 91.7%, 69.8%, and 86.4%, respectively. The specificity of each class in the independent test set was 76.8%, 90.0%, and 83.1%, respectively. The total accuracy was 83.8%. The area under the curve (AUC) of each class was 0.982, 0.907, and 0.960, respectively. The micro-average AUC was 0.957, and the macro-average AUC was 0.949. CONCLUSIONS The normal fetal lung GA grading model could accurately identify ultrasound images of the fetal lung at different GAs, which can be used to identify cases of abnormal lung development due to gestational diseases and evaluate lung maturity after antenatal corticosteroid therapy. The results indicate that DL algorithms can be used as a non-invasive method to predict FLM.
Algorithms ; Deep Learning ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Lung/diagnostic imaging* ; Neural Networks, Computer ; Pregnancy