ABSTRACT
BACKGROUND: Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models. METHODS: We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model. RESULTS: The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813-0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer-Lemeshow goodness-of-fit test showing consistent results (χ2 = 12.212, p = 0.142). CONCLUSION: In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infection in addition to respiratory infections in children with TB who have higher CD3, CD4 and CD8 T-cell counts than the ERTB group. Furthermore, CD4 T-cell counts correlated closely with the severity of chest CT lesions. Age, symptom duration, A/G ratio, Hs-CRP level and NLR were established as independent risk factors for STB. The nomogram model, based on these factors, offers effective discrimination and calibration in predicting STB in children.
Subject(s)
Globulins , HIV Infections , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis , Humans , Child , C-Reactive Protein , T-Lymphocyte Subsets , Tuberculosis/diagnosis , Risk Factors , Lymphocyte Subsets , Lymphocyte CountABSTRACT
BACKGROUND: The incidence of sinonasal adenocarcinoma is low, and there are few studies on survival and prognosis. Therefore, we aim to develop and validate a prognostic model for predicting the overall survival of sinonasal adenocarcinoma and provide guidance for clinical management. METHODS: Patients who were diagnosed as sinonasal adenocarcinoma through Surveillance, Epidemiology, and End Results database between 1975 and 2015 were randomly divided into a training group and validation group. Univariate, multivariate survival analysis was performed to screen independent survival factors. A nomogram was established to predict the overall survival rate of sinonasal adenocarcinoma. Receiver operating characteristic curve and calibration plot were performed to verify the discrimination and accuracy of the model. A decision curve analysis was performed to verify the clinical applicability of the model. RESULTS: A total of 423 patients with sinonasal adenocarcinoma were randomly divided into training group (n = 299) and verification group (n = 124). We established and verified the Nomo map including age, marriage, grade, surgery and tumour size. The c-index of Surveillance, Epidemiology, and End Results stage, T stage and this model are 0.635, 0.626 and 0.803, respectively. The survival rate of the high-risk group scored by this model was lower than that of the low-risk group (P < 0.001). Decision curve analysis shows that the model has advantages in predicting survival rates. CONCLUSION: Our model is considered to be a useful tool for predicting the overall survival of sinonasal adenocarcinoma, with good discrimination and clinical applicability. We hope that this model will help rhinologists to make clinical decisions and manage patients diagnosed with sinonasal adenocarcinoma.
Subject(s)
Adenocarcinoma , Paranasal Sinus Neoplasms , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Humans , Nomograms , Paranasal Sinus Neoplasms/mortality , Paranasal Sinus Neoplasms/surgery , Prognosis , SEER Program , Survival RateABSTRACT
Background: Head and neck squamous cell carcinoma (HNSC) is one of the most common malignancies, and identification of HNSC biomarkers is critical. LIM Domain And Actin Binding 1 (LIMA1) is involved in actin cytoskeleton regulation and dynamics. The role of LIMA1 in HNSC is unclear. This is the first study to investigate the expression of LIMA1 in HNSC patients and its prognostic value, potential biological functions, and impact on the immune system. Methods: Gene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were all based on data from The Cancer Genome Atlas (TCGA) with additional bioinformatics analysis. Statistical analysis was performed using TIMER and ssGSEA to analyze the immune response to LIMA1 expression in HNSCs. In addition, Gene Expression Omnibus (GEO), Kaplan-Meier(K-M) survival analysis, and data from the Human Protein Atlas (HPA) were used to validate the results. Results: LIMA1 played a key role as an independent prognostic factor in HNSC patients. GSEA found that LIMA1 is associated with promoting cell adhesion and suppressing immune function. LIMA1 expression was significantly correlated with infiltration of B cells, CD8+ T cells, CD4+ T cells, dendritic cells, and neutrophils and was coexpressed with immune-related genes and immune checkpoints. Conclusion: The expression of LIMA1 is increased in HNSC, and the high expression of LIMA1 is associated with poor prognosis. LIMA1 may affect tumor development by regulating tumor-infiltrating cells in the tumor microenvironment (TME). LIMA1 may be a potential target for immunotherapy.
ABSTRACT
OBJECTIVE: To explore the survival value of lymph node dissection (LND) in elderly patients with T3-T4 laryngeal cancer, analyze the risk factors of lymph node metastasis, and construct a preoperative prediction model. MATERIALS AND METHODS: The study included 996 patients aged ≥65 years with laryngectomy confirmed T3-T4 laryngeal cancer queried from Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. Propensity score matching (PSM) was applied to balance the effects of confounding factors. Kaplan-Meier (K-M) analysis and competitive risk model were used to compare the overall survival (OS) and cancer-specific survival (CSS) between LND and no-LND (N-LND) group. Combined with risk factors of multivariate logistic regression, a nomogram was built to predict lymph node metastasis preoperatively. The performance was assessed in the training set and the validation set, and internal validation was assessed. RESULTS: Among the cohort, 822 patients underwent LND and 410 patients had positive lymph nodes. The OS and CSS of patients who underwent LND were not better than that of N-LND patients (P>0.05). The prognosis of patients with lymph node metastases was significantly worse than that of negative patients (P<0.05). On multivariate logistic regression, supraglottis cancer, tumor size >5cm and grade 3-4 classification were associated with significantly greater odds of lymph node metastasis. The nomogram showed favorable predictive efficacy and good calibration (in the training cohort C-index=0.700; in the validation cohort C-index=0.721). CONCLUSION: For elderly patients with T3-T4 laryngeal cancer, LND did not bring significant survival values. Supraglottis cancer, tumor size >5cm and grade 3-4 classification were independent risk factors of lymph node metastasis, which means poor prognosis. The nomogram developed was an easy-to-use tool for lymph node prediction.
Subject(s)
Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/surgery , Lymph Node Excision/statistics & numerical data , Lymph Nodes/surgery , Aged , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Neoplasm Staging , Prognosis , Propensity ScoreABSTRACT
Interleukin (IL)-35 modulates the imbalance between regulatory T cells (Tregs) and T helper (Th) 17 cells, which played vital roles in the pathogenesis of autoimmune and infectious diseases. However, the role of Tregs/Th17 cell imbalance and the regulatory functions of IL-35 have remained largely unknown in enterovirus 71 (EV71)-induced hand, foot, and mouth disease (HFMD). In this study, a total of 47 HFMD patients (30 with mild HFMD and 17 with severe HFMD) and 13 healthy individuals were enrolled. The frequencies of CD4+CD25+CD127dim/- Tregs and CD4+IL-17+ Th17 cells, as well as IL-35 expression levels, were measured. Cellular proliferation and cytokine production was also determined in purified Tregs following recombinant IL-35 stimulation. An imbalance between Tregs and Th17 cells was observed in children with severe HFMD, which manifested as a reduction in the Tregs population and an elevation in the Th17 population. Serum IL-35 concentrations were also decreased in case of severe HFMD, which correlated with the Tregs:Th17 cell ratios. Recombinant IL-35 stimulation increased the proportion of Tregs, but downregulated that of Th17 cells. Treatment with IL-35 enhanced Tregs suppressive function and IL-35 and IL-10 expression, but reduced IL-22 secretion in both healthy individuals and those with severe HFMD. The Tregs:Th17 cell ratio was increased in the convalescent patients, however, a significant reduction in serum IL-35 was not observed. Our findings indicated that EV71 infection shifted the Tregs:Th17 cell ratio through IL-35 by downregulating inhibitory cytokine production and reducing the cell-to-cell contact inhibition of effector T cells. Regulation of IL-35 as it relates to the Tregs/Th17 balance may play a critical role in the pathogenesis of EV71-associated HFMD.
Subject(s)
Enterovirus A, Human/immunology , Hand, Foot and Mouth Disease/immunology , Interleukins/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Cell Proliferation , Cells, Cultured , Child, Preschool , Female , Hand, Foot and Mouth Disease/diagnosis , Hand, Foot and Mouth Disease/pathology , Humans , MaleABSTRACT
Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.
Resumo Justificativa e objetivos: Isoflurano é um éter volátil halogenado usado para anestesia por via inalatória. É amplamente usado na clínica como um anestésico para inalação. A lesão hipóxico-isquêmica neonatal ocorre no cérebro imaturo e resulta em morte celular tardia via excitotoxicidade e estresse oxidativo. Isoflurano mostrou ter propriedades neuroprotetoras que formam uma base benéfica para o seu uso tanto em cultura de células quanto em modelos animais, incluindo vários modelos de lesão cerebral. Nosso objetivo foi determinar o efeito neuroprotetor de isoflurano em hipóxia cerebral e elucidar o mecanismo subjacente. Métodos: Fatias de hipocampo, em fluido cerebrospinal artificial (CSFA) com glicose e privação de oxigênio, foram usadas como um modelo in vitro de hipóxia cerebral. O pico de população ortodrômica (PPO) e o potencial de lesão hipóxica (PLH) foram registrados nas regiões CA1 e CA3. A concentração de neurotransmissores de aminoácidos na solução de perfusão das fatias de hipocampo foi medida. Resultados: O tratamento com isoflurano retardou a eliminação do PPO e melhorou a recuperação do PPO; diminuiu a frequência do PLH, retardou o início do PLH e aumentou a duração do PLH. O tratamento com isoflurano também diminuiu a liberação de neurotransmissores de aminoácidos induzida pela hipóxia, como aspartato, glutamato e glicina, mas os níveis de ácido γ-aminobutírico (GABA) estavam elevados. Estudos morfológicos mostram que o tratamento de edema com isoflurano atenuou o edema de neurônios piramidais na região CA1. Também reduziu a apoptose, como mostrado pela expressão reduzida da caspase-3 e genes PARP. Conclusões: Isoflurano mostrou um efeito neuroprotetor na lesão neuronal no hipocampo induzida por hipóxia através da supressão de apoptose.
Subject(s)
Animals , Female , Pregnancy , Rats , Hypoxia, Brain/prevention & control , Brain Ischemia/pathology , Apoptosis/drug effects , Neuroprotective Agents/pharmacology , Anesthetics, Inhalation/pharmacology , Isoflurane/pharmacology , Hypoxia, Brain/pathology , Rats, Sprague-Dawley , CA1 Region, Hippocampal/pathology , CA3 Region, Hippocampal/pathology , Glucose/deficiency , Hippocampus/pathology , Animals, NewbornABSTRACT
BACKGROUND AND OBJECTIVES: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. METHODS: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. RESULTS: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. CONCLUSIONS: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.
Subject(s)
Anesthetics, Inhalation/pharmacology , Apoptosis/drug effects , Brain Ischemia/pathology , Hypoxia, Brain/prevention & control , Isoflurane/pharmacology , Neuroprotective Agents/pharmacology , Animals , Animals, Newborn , CA1 Region, Hippocampal/pathology , CA3 Region, Hippocampal/pathology , Female , Glucose/deficiency , Hippocampus/pathology , Hypoxia, Brain/pathology , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND AND OBJECTIVES: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. METHODS: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. RESULTS: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. CONCLUSIONS: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.
ABSTRACT
The aim of the present study was to observe the mobilisation effects of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells (BMSCs) in rats with renal ischaemia-reperfusion injury. In addition, the effects of the BMSCs on the expression levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were investigated, with the aim to further the understanding of the protective mechanisms of SCF and G-CSF in renal ischaemia-reperfusion injury. The model and treatment groups were established using a model of unilateral renal ischaemia-reperfusion injury, in which the treatment group and the treatment control group were subcutaneously injected once a day with 200 µg/kg SCF and 50 µg/kg G-CSF, 24 h after the modelling, for five consecutive days. The CD34+ cell count was measured in the peripheral blood using flow cytometry. The mRNA expression levels of HGF and EGF were determined using polymerase chain reaction analysis, while the protein expression levels of HGF and EGF were detected using immunohistochemistry. The CD34+ cell count in the peripheral blood of the treatment and treatment control groups was significantly higher compared with that in the model group (P<0.05). However, CD34 expression levels in the cells from the renal tissues of the model and treatment groups were significantly higher compared with that of the control and treatment control groups (P<0.05), with the greatest increase observed in the treatment group. The mRNA and protein expression levels of HGF and EGF in the treatment group were significantly higher compared with the model group (P<0.05). Therefore, the results indicated that a combination of SCF and G-CSF can promote the repair of acute tubular necrosis. This combination, which can mobilise sufficient numbers of BMSCs to migrate back to the injured site, is a key factor in promoting the repair of renal tubular injury. Upregulation of HGF and EGF was also shown to promote the repair of renal tubular injury.
ABSTRACT
OBJECTIVE: To explore the clinical effect of the free radial forearm flap on repairing tissue defects and reconstructing functions after tumor resection.â© METHODS: From January, 2003 to December, 2011, 70 patients, including 43 squamous cell carcinomas of tongue, 12 buccal cancers, 5 carcinomas of the soft palate, 4 basal cell carcinomas of external nose, 3 lower lip cancers, 2 upper lip cancers, and 1 posterior wall of hypopharynx carcinoma, with the soft tissue defects in the head and neck underwent reconstructive operations with the free radial forearm flap after the malignant tumor resection. The area of defects ranged from 5 cm × 4 cm to 14 cm × 8 cm with the process of diseases from 4 to 30 months. The technique for grafting the free radial forearm flap and the appearance at sites of the donor and recipient, and the influence on the anatomy and function in both local sites were analyzed.â© RESULTS: In the 70 patients, only 1 case of flap appeared necrosis due to venous reflux obstacle, and the remaining (98.4 ﹪) survived. During the follow-up for 12-36 months, one case of hypopharyngeal carcinoma died from distant metastasis a year later, 2 cases of tongue cancer died of cardiovascular accident. Morphology and function for the sites at donor and recipient were satisfactory.â© CONCLUSION: Free radical forearm flap is a good choice for the repair and functional reconstruction for tissue defects after tumor resection.
Subject(s)
Head and Neck Neoplasms/surgery , Plastic Surgery Procedures , Skin Transplantation , Surgical Flaps , Forearm , Humans , Treatment OutcomeABSTRACT
AIMS AND BACKGROUND: Chibby (CBY), a ß-catenin binding partner, inhibits Wnt/ß-catenin-mediated transcriptional activation by competing with Tcf/Lef factors for ß-catenin binding and promoting the export of ß-catenin from nucleus to cytoplasm. The regulatory effect of CBY in this signaling pathway suggests its biological importance as a potential tumor suppressor gene. The purposes of this study were to determine whether the expression of CBY was downregulated in human laryngeal squamous cell carcinoma (LSCC) samples, the CpG sites of CBY at the promoter region were methylated in these tumor samples, and reduced expression of CBY was induced by methylation of CBY promoters. METHODS: CBY expression was investigated by quantitative real-time PCR and immunohistochemistry in samples from 36 LSCC patients. The methylation status of the CBY promoter was detected by methylation-specific PCR. RESULTS: Compared with normal laryngeal mucosa, the expression of CBY was downregulated in LSCC samples. The reduced CBY expression rate was 58.33% (21/36) at the mRNA and 66.67% (24/36) at the protein level. The promoters of CBY were methylated in 12/36 tumor samples, partially methylated in 5, and unmethylated in 19 samples. The methylation rate including incomplete methylation was 47.22% (17/36) in tumor samples, while no methylation was detected in normal laryngeal squamous epithelium. Compared with the unmethylated group, the expression of CBY was significantly different in the methylated group (p<0.05) but similar in the partially methylated group (p>0.05). CONCLUSIONS: Our data indicate that CBY expression was downregulated in LSCC, which may be partially caused by methylation of CBY promoters.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Carrier Proteins/metabolism , DNA Methylation , Laryngeal Neoplasms/metabolism , Nuclear Proteins/metabolism , Promoter Regions, Genetic , Adult , Aged , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carrier Proteins/genetics , CpG Islands/genetics , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Nuclear Proteins/genetics , Promoter Regions, Genetic/genetics , Real-Time Polymerase Chain ReactionABSTRACT
The aim of this study was to investigate the effects of erythropoietin (EPO) on the impairment of autophagy induced by lipopolysaccharide (LPS) in primary cultured rat glomerular mesangial cells (GMCs). Rat GMCs were isolated and cultured in normal glucose, high-glucose, LPS or LPS + EPO medium. At 24 and 72 h of culture, the cells were examined for expression levels of the autophagy markers LC3 and p62/sequestosome-1 (SQSTM1) using western blot analysis. At 24 h, no significant difference in the expression of LC3 and p62/SQSTM1 was observed among the groups; however, the cells exposed to high-glucose medium for 72 h showed downregulated LC3 expression and upregulated p62/SQSTM1 expression. The cells exposed to LPS (10 ng/ml) for 72 h showed upregulated LC3 expression and upregulated p62/SQSTM1 expression. These changes were reversed in the LPS + EPO group at 72 h. In conclusion, EPO can inhibit LPS-induced autophagy in rat GMCs.
ABSTRACT
When confronting the complex problems, radial basis function (RBF) neural network has the advantages of adaptive and self-learning ability, but it is difficult to determine the number of hidden layer neurons, and the weights learning ability from hidden layer to the output layer is low; these deficiencies easily lead to decreasing learning ability and recognition precision. Aiming at this problem, we propose a new optimized RBF neural network algorithm based on genetic algorithm (GA-RBF algorithm), which uses genetic algorithm to optimize the weights and structure of RBF neural network; it chooses new ways of hybrid encoding and optimizing simultaneously. Using the binary encoding encodes the number of the hidden layer's neurons and using real encoding encodes the connection weights. Hidden layer neurons number and connection weights are optimized simultaneously in the new algorithm. However, the connection weights optimization is not complete; we need to use least mean square (LMS) algorithm for further leaning, and finally get a new algorithm model. Using two UCI standard data sets to test the new algorithm, the results show that the new algorithm improves the operating efficiency in dealing with complex problems and also improves the recognition precision, which proves that the new algorithm is valid.
Subject(s)
Algorithms , Models, Neurological , Neural Networks, Computer , Neurons/physiology , Computer Simulation , Humans , Least-Squares Analysis , Support Vector MachineABSTRACT
Chibby (Cby) inhibits Wnt/ß-catenin-mediated transcriptional activation by competing with Lef-1 (the transcription factor and target of ß-catenin) to bind to ß-catenin. This suggests that Cby could be a tumor suppressor protein. In the present study, we examined Cby expression in laryngeal squamous cell carcinoma (LSCC) and its function and mechanism in laryngeal carcinoma cell lines. Cby expression levels were investigated by immunohistochemistry in a panel of 36 LSCC patient cases. The expression of ß-catenin, c-myc and cyclin D1 in Hep-2 were determined through RT-PCR and western blot analysis. Activity of Wnt/ß-catenin signaling pathway after overexpression of Cby was measured by TCF/LEF luciferase reporter gene assay. Proliferation, clone forming ability, cell cycle distribution and cell apoptosis of Hep-2 cells were detected by MTT assay, plate colony forming assay, flow cytometry and TUNEL assay, respectively. This study showed that expression of Cby protein was strongly downregulated in LSCC tumor tissues in comparison to normal laryngeal mucosa samples. No significant correlation was found between the expression of Cby in tumor tissue and gender, age, clinical stage and tumor differentiation of laryngeal cancer patients. When Cby was overexpressed in Hep-2 cells, the expression of cyclin D1 was reduced and ß-catenin activity was inhibited. Proliferation and plate colony forming assays revealed a significant inhibitory effect of Cby on growth and colony formation ability of Hep-2 cells after Cby overexpression in comparison to control and mock-infected cells. In addition, we also found that upregulated expression of Cby resulted in accumulation of numbers of cells in G0/G1 phase with concomitant decrease in S phase by cell cycle assay. TUNEL staining demonstrated that, compared with the control group, the rate of apoptosis in the plv-cs2.0-Cby group was significantly increased. Taken together, downregulation of Cby was observed in LSCC, but with no significant correlation to the clinicopathological features of LSCC patients. Overexpression of Cby effectively suppressed laryngeal carcinoma cell growth and promoted its apoptosis. A better understanding of the mechanisms of Cby gene activation in LSCC could provide potential novel therapeutic targets for human laryngeal carcinoma.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Carrier Proteins/genetics , Carrier Proteins/metabolism , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Adult , Aged , Apoptosis , Carcinoma, Squamous Cell/pathology , Cyclin D1/metabolism , Female , Hep G2 Cells , Humans , Laryngeal Neoplasms/pathology , Male , Middle Aged , Wnt Signaling PathwayABSTRACT
High-dimensional large sample data sets, between feature variables and between samples, may cause some correlative or repetitive factors, occupy lots of storage space, and consume much computing time. Using the Elman neural network to deal with them, too many inputs will influence the operating efficiency and recognition accuracy; too many simultaneous training samples, as well as being not able to get precise neural network model, also restrict the recognition accuracy. Aiming at these series of problems, we introduce the partial least squares (PLS) and cluster analysis (CA) into Elman neural network algorithm, by the PLS for dimension reduction which can eliminate the correlative and repetitive factors of the features. Using CA eliminates the correlative and repetitive factors of the sample. If some subclass becomes small sample, with high-dimensional feature and fewer numbers, PLS shows a unique advantage. Each subclass is regarded as one training sample to train the different precise neural network models. Then simulation samples are discriminated and classified into different subclasses, using the corresponding neural network to recognize it. An optimized Elman neural network classification algorithm based on PLS and CA (PLS-CA-Elman algorithm) is established. The new algorithm aims at improving the operating efficiency and recognition accuracy. By the case analysis, the new algorithm has unique superiority, worthy of further promotion.
Subject(s)
Algorithms , Cluster Analysis , Least-Squares Analysis , Neural Networks, Computer , Computer Simulation , Data Interpretation, Statistical , HumansABSTRACT
OBJECTIVE: To explore the correlations between Chlamydia pneumoniae (CP) infection and IgA nephropathy (IgAN). METHODS: Seventy patients with primary IgAN were enrolled in the study. Seventy serum specimens from healthy blood donors and twelve renal autopsy specimens from accidental death bodies were regarded as control groups. Serum CP IgG and CP IgA antibody titers were detected by indirect immunofluorescence. CP DNA of renal tissue was measured by fluorescent quantitative PCR. Finally, using statistical methods, we analyzed the correlations of CP infection and CP DNA of renal tissue with clinical manifestations and kidney pathological changes of IgAN patients. RESULTS: The rate of CP persistent infection in IgAN group was higher than that of healthy blood donor group (P<0.01). The rate was not significantly different within the IgAN group, such as among acute infection, previous infection and no infection subgroups (P>0.05). It was higher in the patients with gross proteinuria and/or durative renal insufficiency than in non-gross proteinuria patients (P<0.05). The scores of glomerular patholopical and tubulointerstitial injury of CP persistent infection patients were higher than those of non-persistent infection ones (P<0.05). The renal injury of CP persistent infection patients was more severe than that of non-persistent infection ones. The positive rate of CP DNA in gross proteinuria and/or renal insufficiency patients was higher than that of non-gross proteinuria patients (P<0.05). The scores of glomerular pathological and tubulointerstitial injury of positive CP DNA patients were respectively higher than those of negative CP DNA ones (P<0.05, P<0.01). The renal injury of patients with positive CP DNA was more severe than that of negative CP DNA ones. CP persistent infection was obviously correlated with renal CP DNA (P<0.01). CONCLUSION: Primary IgAN is associated with CP persistent infection, but not with CP previous infection or CP acute infection.
Subject(s)
Antibodies, Bacterial/immunology , Chlamydophila Infections/immunology , Chlamydophila pneumoniae/immunology , Glomerulonephritis, IGA/immunology , Adolescent , Adult , Antibodies, Bacterial/blood , Child , Chlamydophila Infections/blood , Chlamydophila Infections/microbiology , Chlamydophila pneumoniae/genetics , Chlamydophila pneumoniae/physiology , DNA, Bacterial/genetics , DNA, Bacterial/immunology , Female , Fluorescent Antibody Technique, Indirect , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/microbiology , Host-Pathogen Interactions/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Kidney Glomerulus/immunology , Kidney Glomerulus/microbiology , Kidney Glomerulus/pathology , Male , Polymerase Chain Reaction/methods , Young AdultABSTRACT
OBJECTIVE: To observe the level in plasma hydrogen sulfide (H2S) and the expression of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) (two key synthetases for endogenous H2S generation in the kidney) in obstructed kidney tissue among rats with tubulointerstitial fibrosis (TIF) induced by unilateral ureteral obstruction (UUO), and to explore the role of H2S in TIF. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into sham-operated, model, low-dose NaHS and high-dose NaHS groups (n=24 each). TIF was induced by UUO in the model, low-dose NaHS and high-dose NaHS groups. The low-dose and high-dose NaHS groups were intraperitoneally injected with NaHS (1.4 and 7.0 µmol/kg respectively) twice daily immediately after operation, and the sham-operated and model groups were intraperitoneally injected with an identical volume of normal saline. In each group, 8 rats were randomly selected and sacrificed at 7, 14 or 21 days after operation. Plasma H2S concentration was measured by deproteinization. The obstructed kidney tissue was subjected to hematoxylin and eosin staining and Masson staining, and the renal tubulointerstitial injury was evaluated under a microscope. mRNA and protein expression of CBS and CSE in the obstructed kidney tissue was measured by RT-PCR and immunohistochemistry respectively. RESULTS: The degree of UUO-induced renal tubulointerstitial injury was negatively correlated with plasma H2S concentration in (r=-0.891, P<0.01). With H2S supplementation, renal tubulointerstitial injury was reduced (P<0.01), the expression of mRNA and protein of CBS and CSE in the kidney tissue and plasma H2S level were upregulated (P<0.01), and the degree of TIF was reduced (P<0.01). There were no significant differences in plasma H2S level and mRNA and protein expression of CBS and CSE between the low-dose and high-dose NaHS groups (P>0.05). CONCLUSIONS: H2S is involved in the development of UUO-induced TIF, and the CBS/H2S and CSE/H2S systems play key roles in this process. H2S supplementation can delay the progression of TIF.
Subject(s)
Hydrogen Sulfide/blood , Kidney Tubules/pathology , Ureteral Obstruction/blood , Animals , Cystathionine beta-Synthase/analysis , Cystathionine beta-Synthase/genetics , Cystathionine gamma-Lyase/analysis , Cystathionine gamma-Lyase/genetics , Dietary Supplements , Fibrosis , Hydrogen Sulfide/administration & dosage , Male , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Ureteral Obstruction/pathologyABSTRACT
This paper proposes a novel ridge-adding-based approach for handling singularities that are frequently encountered in the powerful SVMpath algorithm. Unlike the existing method that performs linear programming as an additional step to track the optimality condition path in a multidimensional feasible space, our new approach provides a simpler and computationally more efficient implementation, which needs no extra time-consuming procedures other than introducing a random ridge term to each data point. Contrary to the existing ridge-adding method, which fails to avoid singularities as the ridge terms tend to zero, our novel approach, for any small random ridge terms, guarantees the existence of the inverse matrix by ensuring that only one index is added into or removed from the active set. The performance of the proposed algorithm, in terms of both computational complexity and the ability of singularity avoidance, is manifested by rigorous mathematical analyses as well as experimental results.
ABSTRACT
OBJECTIVE: To study the repair and functional reconstruction of oropharyngeal defects after resection of advanced-stage tonsillar cancer, and to select the donor site of appropriate flap. METHODS: Between October 2000 and February 2010, 13 patients with advanced-stage tonsillar cancer were treated, including 5 cases of high differentiation squamous cell carcinomas and 8 cases of medium differentiation squamous cell carcinomas. There were 11 males and 2 females, with an average age of 53.6 years (range, 39-67 years). According to Union for International Cancer Control (UICC) 1997 standards of oropharyngeal cancer, 1 case was classified as T1N1M0, 2 as T2NIM0, 2 as T2N2M0, 3 as T3N1M0, 2 as T3N2M0, 2 as T4N1M0, and 1 as T4N2M0. The disease duration was 1-8 months with an average of 4.3 months. The tumor invaded lateral wall of nasopharyngeal in 1 case, lateral wall of hypopharynx in 3 cases, epiglottis in 1 case, soft palate in 4 cases, and tongue root in 3 cases. The tumor infiltrating range was from 2 cm x 2 cm to 12 cm x 6 cm. All the 13 cases underwent integrated methods of surgery and postoperative radiotherapy. After resection of tumor by combined neck-mandible-oral cavity approach, pectoralis major myocutaneous flaps were transplanted in 5 cases, forearm free skin flaps in 5 cases, and anterolateral thigh free skin flaps in 3 cases. RESULTS: The postoperative pathological results showed 10 cases of cervical lymph node metastasis; 2 cases had local recurrence and 3 cases had cervical lymph node metastasis after postoperative radiotherapy. Neck infection occurred at 5 days after operation in 1 case undergoing transplantation of pectoralis major myocutaneous flap, and vascular crisis occurred at 12 hours after operation in 1 case undergoing transplantation of forearm free skin flap, which were cured after correspondent treatments. The other flaps survived with incision healing by first intention. Second suture was carried out in 1 case undergoing anterolateral thigh free skin flap transplantation because of wound disruption at the donor site. All the patients were followed up 1 to 6 years, with an average of 3.6 years. In 5 cases undergoing pectoralis major myocutaneous flap transplantation, swallowing obstruction and stomatolalia occurred. In 8 cases undergoing free skin flaps transplantation, the appearances of the flaps and the functions of swallowing or speaking were satisfactory, with no dysfunction at the donor site. All the patients returned to normal occlusion, facial appearance and function were normal. According to the direct calculation method, the three-year survival rate was 60.0% (6/10), and five-year survival rate was 37.5% (3/8). CONCLUSION: For the patients with advanced-stage tonsillar cancer, forearm free skin flaps, or anterolateral thigh free skin flaps is the first choice for repairing defect. However, it is better to choose pectoralis major myocutaneous flaps in patients who need large flap and fail to radiotherapy.
Subject(s)
Carcinoma, Squamous Cell/surgery , Plastic Surgery Procedures/methods , Tonsillar Neoplasms/surgery , Adult , Aged , Carcinoma, Squamous Cell/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Skin Transplantation , Surgical Flaps , Tonsillar Neoplasms/pathologyABSTRACT
OBJECTIVE: To observe the expression of HPA, bFGF and VEGF in nasopharyngeal angiofibroma, and then explore its significance of inducing angiogenesis in the tumor's expansibility growth. METHOD: The expression of heparanase, bFGF, VEGF and CD105 were examined in 30 (I - II period 9 cases, III - IV period 21 cases) samples from nasopharyngeal angiofibroma and 20 inferior turbinate tissues by immunohistochemical staining technique. The microvascular density (MVD) were measured by the immunohistostaining of CD105. The MVD was analyzed with the clinical stage. RESULT: The positive rates of the HPA, bFGF and VEGF expression in JNA tissues were significantly higher than that in inferior turbinate group (P < 0.05). The positive rates of HPA, bFGF and VEGF expression in III - IV period were obviously higher than that in I - II period (P < 0.05). The expression of bFGF and VEGF in JNA tissues was respectively positive correlated with the HPA (r = by 0.499, 0.582, P < 0.05); In JNA tissues, the mean MVD in both HPA and bFGF positive group was higher than each one single positive group or both negative express group (P < 0.05). And the mean MVD in both HPA and VEGF positive group was higher than each one single positive group or both negative express group (P < 0.05). CONCLUSION: HPA can induce angiogenesis to promote tumor growth by releasing bFGF and VEGF. Targeting the HPA can be a new direction in JNA adjuvant treatment.