Hydrogen sulfide mitigates memory impairments via the restoration of glutamatergic neurons in a mouse model of hemorrhage shock and resuscitation.

Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased ß power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored ß power. Moreover, hydrogen sulfide (H2S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H2S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased ß power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H2S may be useful therapeutic approaches for improving memory deficits following HSR.

Immobilization enhancement of heavy metals in lightweight aggregate by component regulation of multi-source solid waste.

Integrated recycling of solid waste containing heavy metals is a critical environmental challenge. In this study, a green solution to reduce heavy metal leaching from solid waste is demonstrated by combining contaminated soil, industrial sludge and lithium slag in pairs to produce lightweight aggregates (LWAs). The physical properties and heavy metal leaching behavior of LWA samples were systematically investigated and characterized. The results showed that industrial sludge reduced the density and water absorption of LWA, while the high content of lithium slag was detrimental to the physical properties. LWA containing 80% contaminated soil and 20% lithium slag had the lowest particle density of 1.47 g/cm3 due to the hollow structure caused by the low viscosity and violent generation of SO2. LWAs with lithium slag leached excessive Cu and Cr relatively, while heavy metals were immobilized well in LWAs with contaminated soil and industrial sludge as the main components. Because the flux components of industrial sludge could enhance the encapsulation of heavy metals by glass phase. In addition, the co-immobilization of multiple heavy metals was observed in the spinel phase. This study provides an efficient and safe method for the synergistic recycling of solid waste.

Study on Photochemical Properties of a Sr-SnS2/CaIn2S4 Heterostructure to Improve Cr(VI) Removal.

Compound semiconductor photocatalysis technology is considered to be a promising treatment for solving water problems efficiently. The point of designing high-efficiency catalysts is to optimize the band gap structure and facilitate the separation of charge carriers by establishing new electron migration pathways. Recently, 3D porous CaIn2S4 was found to have good photocatalytic ability. However, the quick recombination and agglomeration of carriers still limit its application. Herein, we prepared a heterostructure by introducing 2D Sr-doped SnS2 to 3D CaIn2S4 by a hydrothermal synthesis method. The optimal dosage of Sr-SnS2 is 3%, and the photocatalytic Cr(VI) removal efficiency of 3% Sr-SnS2/CaIn2S4 (SSCS-3) is 5.82 and 10.83 times those of pure CaIn2S4 and SnS2, respectively. According to the results of characterization tests and calculation verification, we inferred that the enhanced photocatalytic removal of Cr(VI) is due to the introduction of Sr-SnS2 that can promote the rapid transfer of photogenerated electrons to the surface of CaIn2S4, and the heterostructure formed between 2D Sr-SnS2 and 3D CaIn2S4 can also provide abundant reaction sites. The promotion of carrier separation is mainly due to the formation of a built-in electric field of the Sr-SnS2/CaIn2S4 heterostructure. This work provides new ideas and technologies for the treatment of Cr(VI) in wastewater.

Dynamic three-sided matching model for personnel-robot-position matching problem in intelligent environments.

In recent years, intelligent robots have facilitated intelligent production, and a new type of problem (personnel-robot-position matching (PRPM)) has been encountered in personnel-position matching (PPM). In this study, a dynamic three-sided matching model is proposed to solve the PRPM problem in an intelligent production line based on man-machine collaboration. The first issue considered is setting the dynamic reference point, which is addressed in the information evaluation phase by proposing a method for setting the dynamic reference point based on the prospect theory. Another important issue involves multistage preference information integration, wherein a probability density function and a value function are introduced. Considering the attenuation of preference information in a time series, the attenuation index model is introduced to calculate the satisfaction matrix. Furthermore, a dynamic three-sided matching model is established. Additionally, a multi-objective decision-making model is established to optimize the matching of multiple sides (personnel, intelligent robots, and positions). Subsequently, the model is transformed into a single objective model using the triangular balance principle, which is introduced to obtain the final optimisation results in this modelling process. A case study is presented to illustrate the practicality of the dynamic three-sided matching model in intelligent environments. The results indicate that this model can solve the PRPM problem in an intelligent production line.

PHF5A facilitates the development and progression of gastric cancer through SKP2-mediated stabilization of FOS.

BACKGROUND: Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide. Plant homeodomain (PHD)-finger domain protein PHF5A has been demonstrated to play a promoting role in a variety of cancers. This study aimed to clarify the role of PHF5A in the progression of GC and its potential mechanism of action. METHODS: Immunohistochemical staining experiments were performed based on tissues from clinical GC patients to reveal PHF5A expression. A series of functional experiments in vitro and in vivo were used to clarify the role of PHF5A in GC. RESULTS: Clinically, PHF5A was abundantly expressed in GC and existed clinical value indicating poor prognosis. In addition, GC cells with knockdown of PHF5A expression showed slowed proliferation, enhanced sensitivity to apoptosis and inhibition of migration. Mechanically, knockdown of PHF5A led to decreased protein stability of FOS, which was mediated ubiquitination of E3 ubiquitin ligase S-phase kinase-associated protein 2 (SKP2). Moreover, downregulation of FOS attenuated the promotion of PHF5A overexpression on GC cells. Consistently, Pladienolide B (PHF5A inhibitor) treatment reversed the induction of PHF5A overexpression on the malignant phenotypes and tumor formation of GC cells. CONCLUSION: Knockdown of PHF5A inhibited the progression of GC through SKP2-mediated ubiquitination of FOS, which may be a promising candidate target with potential therapeutic value.

Design of early warning system for mental health problems based on data mining and database / Projeto de sistema de alerta precoce para problemas de saúde mental com base na mineração de dados e banco de dados / Diseño de un sistema de alerta temprana de problemas de salud mental basado en la minería de datos y en la base de datos

ABSTRACT Introduction: Data mining technology is mainly employed in the era of big data to evaluate the acquired information. Subsequently, reasoning about the data inductively is fully automated to discover possible patterns. Objective: Recently, data mining technology in the national mental health database has deepened and can be effectively used to solve various mental health early warning problems. Methods: For example, it can be applied to mine psychological data and extract the most important features and information. Results: This paper presents the design of an early warning system for mental health problems based on data mining techniques to offer some thoughts on early warning of mental health problems, including data preparation, data mining, results in analysis, and decision tree algorithm. Conclusion: The experimental results indicate that the results of the early warning system in this paper can achieve an accuracy rate of more than 96% with a high accuracy rate. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

RESUMO Introdução: A tecnologia de mineração de dados é empregada principalmente na era da big data para avaliar as informações adquiridas. Posteriormente, raciocinar indutivamente sobre os dados de forma totalmente automatizada para descobrir possíveis padrões. Objetivo: Recentemente, a tecnologia de mineração de dados no banco de dados nacional de saúde mental tem se aprofundado e pode ser efetivamente utilizada para resolver vários problemas de alerta precoce da saúde mental. Métodos: Por exemplo, ela pode ser aplicada para a mineração de dados psicológicos e extrair as características e informações mais importantes. Resultados: Este documento apresenta o projeto de um sistema de alerta precoce para problemas de saúde mental baseado em técnicas de mineração de dados, com o objetivo de oferecer algumas reflexões sobre alerta precoce de problemas de saúde mental, incluindo preparação de dados, mineração de dados, análise de resultados e algoritmo de árvore de decisão. Conclusão: Os resultados experimentais indicam que os resultados do sistema de alerta precoce neste trabalho podem alcançar uma taxa de precisão de mais de 96% com uma alta taxa de precisão. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

Resumen Introducción: La tecnología de minería de datos se emplea principalmente en la era de la big data para evaluar la información adquirida. Posteriormente, razonar inductivamente sobre los datos de forma totalmente automatizada para descubrir posibles patrones. Objetivo: Recientemente, la tecnología de minería de datos en la base de datos nacional de salud mental se ha profundizado y puede ser utilizada eficazmente para resolver varios problemas de alerta temprana de salud mental. Métodos: Por ejemplo, puede aplicarse para minar datos psicológicos y extraer las características e información más importantes. Resultados: Este trabajo presenta el diseño de un sistema de alerta temprana de problemas de salud mental basado en técnicas de minería de datos, con el objetivo de ofrecer algunas reflexiones sobre la alerta temprana de problemas de salud mental, incluyendo la preparación de los datos, la minería de datos, el análisis de los resultados y el algoritmo de árbol de decisión. Conclusión: Los resultados experimentales indican que los resultados del sistema de alerta temprana de este documento pueden alcanzar un índice de precisión superior al 96% con un alto índice de precisión. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Online Loan Default Prediction Model Based on Deep Learning Neural Network.

With the rapid development of Internet loans and the demand for Internet loans, Internet-based loan default prediction is particularly important. P2P online lending is based on Internet technology. With the popularization of personal PCs and mobile terminals, the borrower's financing cost has been reduced to a large extent, and the efficiency of the borrower's capital utilization has also been improved to a considerable level. Making full use of the existing data of the online lending platform, integrating third-party data, and predicting the default behavior of users are the major directions of future development. This paper mainly studies the network loan default prediction model based on DPNN. This paper first analyzes the problems and risks of the P2P online lending platform, then introduces the principle and characteristics of BPNN in detail, and determines the credit risk rating process for online lending based on BPNN. With the help of data analysis and processing software, after cleaning and variable selection of credit customer data provided by lending clubs, a set of corresponding online lending default risk assessment models are established through BPNN. This paper simulates the network loan default assessment model of the BPNN model and compares it with the support vector machine and regression model. The experimental results show that the highest accuracy rate of the BPNN model is 98.01% and the highest recall rate is 99.82%, which is better than the other two models; the AUC value of BPNN is 0.79, which is significantly higher than that of support vector machine and regression model. The above results show that the online loan default prediction model based on DPNN has high application value in practice. Predicting the probability of customer default risk in advance will help reduce the risk of P2P companies and lenders, improve the competitiveness of P2P lending institutions, and promote the development of domestic P2P platforms to be more stable.

Graphene oxide leads to mitochondrial-dependent apoptosis by activating ROS-p53-mPTP pathway in intestinal cells.

Owing to its unique physical and chemical properties, graphene oxide (GO) has a wide range of applications in biomedical field. However, with the gradual improvement of biosafety investigations on nanomaterials, growing literatures have pointed out that GO could lead to oxidative stress, aggravation of inflammatory responses, and even irreversible lesions in human multi-tissues, while its damage to small intestinal remained unclear. In this study, we conducted an in-depth study on the toxicological effect of GO on intestinal tissues, and further clarified its toxic effect and molecular mechanism on inducing intestinal cell death. Firstly, we characterized the shape size, potential value, Fourier Transform infrared spectroscopy (FT-IR) characterization and pro-oxidant properties of GO nanosheets. The cytotoxicity of different concentrations of GO to Caco-2 and IEC-6 cell lines was thereafter observed, which was specifically manifested as invoking NADPH Oxidase 1 (NOX1) proteins, accompanied generation of reactive oxygen species (ROS). Since that, more p53 flowed into mitochondria to combine with cyclophilin D (CYPD), thus induced mitochondrial permeability transition pore (mPTP) opening. Through ROS-CyPD-mPTP signaling pathway, GO exerted imbalance of mitochondrial homeostasis, while released cytochrome c (CytC) would ultimate caspase-dependent cell apoptosis. In vivo experiment also confirmed that the microstructure of small intestine was damaged, and the apoptosis rate and oxidative markers were significantly increased in GO-treated Sprague- Dawley (SD) rats (40 mg/kg once every other day from day 1 to day 9 by oral gavage). Based on these findings, we conclude that the adverse effects of oral exposure of GO on the biological system mainly concentrate in the digestive tract, and clarify the key role of ROS-mitochondrial homeostasis-apoptosis axis in GO-derived intestinal toxicity. Considering all these results and the fact that GO exhibited intestinal toxicity, we believe that this research providing a safety reference for its biomedical applications.

Corrigendum: LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis.

[This corrects the article DOI: 10.3389/fmed.2021.795427.].

LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis.

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p < 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25-2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03-2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057-2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.

Long Non-coding RNA LINC00115 Contributes to the Progression of Colorectal Cancer by Targeting miR-489-3p via the PI3K/AKT/mTOR Pathway.

Long non-coding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. In this study, we discovered that LINC00115 was significantly overexpressed in CRC, and its overexpression predicted poor patient outcomes. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. Importantly, by luciferase reporter assay, we found that miR-489-3p might directly target LINC00115, and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. In conclusion, our findings demonstrated that LINC00115 serves as an oncogene in CRC metastasis. Deeper understanding of the LINC00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastasis.

Effect of flux components of lightweight aggregate on physical properties and heavy metal solidification performance.

The preparation of lightweight aggregate (LWA) by high-temperature sintering is a promising method for recycling solid waste safely, especially for solidifying heavy metals effectively. The main aim of this research was to systematically evaluate the effects of the flux components on LWA, including Na2O, MgO, CaO, and Fe2O3. The physical properties and chromium solidification mechanism of LWA were characterized and analyzed. The results showed that the addition of Na facilitated LWA preparation and Cr solidification, whereas Ca, Mg, and Fe were deleterious to some extent. Further analysis indicated that increasing the Fe2O3 content was not conducive to the reduction of Cr because its decomposition reaction creates an oxygen-rich environment. The results of this research could provide a meaningful guide for regulating the composition of raw materials for the production of LWA to treat industrial Cr-containing solid waste.

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson's Disease: a Network Meta-Analysis.

BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the evidence from direct comparisons and indirect comparisons and evaluated the pooled weighted mean difference (WMD) values and surfaces under the cumulative ranking curves (SUCRA). The network meta-analysis included 21 RCTs. RESULTS: The analysis results indicated that, using the United Parkinson's Disease Rating Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than that of apomorphine (WMD = -10.90, 95% CI = -16.12∼-5.48; WMD = -11.85, 95% CI = -17.31∼-6.16; WMD = -11.15, 95% CI = -16.64∼-5.04; WMD = -11.70, 95% CI = -16.98∼-5.60; WMD = -11.04, 95% CI = -16.97∼-5.34; WMD = -13.27, 95% CI = -19.22∼-7.40; WMD = -10.25, 95% CI = -15.66∼-4.32; and WMD = -11.60, 95% CI = -17.89∼-5.57, respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a control, on PD exhibited no significant differences on PD symptoms when the UPDRS II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and levodopa treatments, with placebo as a control, indicated that bromocriptine showed the best efficacy on the non-motor symptoms of PD (75.6%). CONCLUSION: Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, apomorphine may be the most efficacious drug for therapy in treating the non-motor symptoms of PD.

Adverse effects produced by different drugs used in the treatment of Parkinson's disease: A mixed treatment comparison.

OBJECTIVE: This mixed treatment comparison is used to compare the adverse effects of eleven different drugs used to treat Parkinson's disease (PD). The drugs that we compare include the following: ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil, pergolide, and levodopa. METHODS: PubMed, EMBASE, and Cochrane Library were searched from the inception to December 2015. Our analysis combines the evidences of direct comparison and indirect comparison between various literatures. We evaluated the merging odds ratios (OR) value and surface under the cumulative ranking curves (SUCRA) of each of the drugs and used this as a mode of comparison. RESULTS: Twenty-four randomized controlled trials (RCTs) were included in this study. Our results demonstrated that the incidence of adverse reactions of ropinirole, rotigotine, entacapone, and sumanirole were obviously higher in terms of nausea compared to the placebo. Ropinirole produced the highest incidence rates of dyskinesia side effects, whereas pramipexole was significantly higher in terms of patients' hallucination. In addition, the SUCRA values of all the drugs showed that the incidence of adverse reaction of pergolide was relatively high (nausea: 83.5%; hallucination: 79.8%); for dyskinesia and somnolence, the incidence of ropinirole was higher (dyskinesia: 80.5%; somnolence: 69.4%); the incidence of adverse reaction of piribedil was higher on PD in terms of dizziness (67.0%); and the incidence of bromocriptine was relatively high in terms of constipation (62.3%). CONCLUSIONS: This mixed treatment comparison showed that the drugs ropinirole, bromocriptine, and piribedil produced the highest incidence rates of nausea, dyskinesia, hallucination, dizziness, constipation, and somnolence symptoms. Thus, we conclude that as these three drugs produced the most frequent symptoms, they are not recommended for the treatment of patients with Parkinson's disease.

Clinical curative effect of oxaliplatin combined with flurouracil in the treatment of gastrointestinal tumor.

Aiming at exploring clinical curative effect of oxaliplatin combined with flurouracil in the treatment of gastrointestinal tumor, this study divided 60 patients with gastrointestinal tumor into control and observation groups, each containing 30 patients. The observation group was treated with oxaliplatin combined with flurouracil, while the control was treated with FOLFOX4, i.e., intravenously dropping 85mg/m(2)Oxaliplatin (L-OHP), 200mg/m(2) calcium folinate (CF) and intravenously injecting 400mg/m(2) 5-fluorouracil (5-Fu), and 600mg/m(2) 5-Fu; then continuously performing intravenous drop infusion for 22h, every two weeks for a cycle. Hypodermic injection of granulocyte colony-stimulating factor (G-CSF) was conducted immediately when leukocytes occurred the III, IV degree of inhibition. The observation results of curative effect and negative reaction indicated higher effective rate with 83.33% in the observation and 50.00% in the control. Besides, in the observation, negative reactions possessed 10.00% that was much lower than 33.33% in the control. Thereby, the conclusion reached that the treatment of gastrointestinal tumor with oxaliplatin combined with flurouracil was worth promoting.

Effect of miR27a on proliferation and invasion in colonic cancer cells.

The aim of this study was to detect the expression of miR196a, miR146a, miR27a and miR200a in patients with colon cancer, and investigate the effect of miR27a expression on proliferation and invasion in colonic cancer cells. RT-PCR was employed to detect the expression levels in colon cancers. Then, colon cancer cells were cultured and transfected with 100 nM of miR27a mimics (80 nmol/L) or 80 nM miR27a inhibitors (80 nmol/L) in 24-well plates. Proliferation and invasion of colonic cancer cells were then determined by CCK-8 and Transwell assays, respectively. Our data showed miR27a to be high-expressed in patients with colon cancer. In addition, proliferation and invasion in the miR27a mimic group were significantly higher than in the control group and negative group (P<0.05), while, proliferation and invasion in the miR27a inhibitor group were obviously lowered (P<0.05). In conclusion, high expression of miR27a may play an important role in enhancing proliferation and invasion of colon cancer cells.

[A controlled study on the treatment of acute progressive cerebral infarction by continuous anticoagulation with small doses of heparin].

OBJECTIVE: To discuss the treatment of acute progressive cerebral infarction by continuous anticoagulation with small doses of heparin. METHODS: A prospective, randomized, and controlled clinical research was conducted. Three hundred and fifty-one patients were randomly divided into three groups. Group A (n=119) was treated with heparin, which was controlled by an infusion pump with a speed of 18 U×kg(-1)×h(-1) for 24 hours, and the dosage was regulated according to the changes in activated partial thromboplastin time (APTT) which was determined every 8 hours. Group B (n=115) was treated with intravenous drip of 12,500 U of heparin with a speed of 18 U×kg(-1)×h(-1) once a day. Group C (n=117) was treated with 5000 U of low-molecular-weight heparin calcium injection twice a day. After 14 days, nerve function defect according to the National Institutes of Heath stroke scale (NIHSS) score was determined, the adverse events (e.g. intracranial hemorrhage, subcutaneous ecchymosis, gingival bleeding, hematuria and occult blood in stools) were observed. After 6 months, the recurrence rate and Barthel index (BI) would be determined. RESULTS: The total efficiency in group A (95.80%) was significantly higher than that in group B (85.22%) and group C (85.47%). Recurrence rate in group A (1.68%) was significantly lower than group B (8.70%) and group C (8.33%) with significant differences (P<0.05 or P<0.01), while there was no significant difference between group B and group C (both P>0.05). The BI of group A (89.27±8.56) was significantly higher than group B (72.57±9.77) and group C (71.66±9.37) with significant difference (both P<0.01), while there was no significant difference between group B and group C (P>0.05). Adverse event rate in group A (5.88%) was slightly higher than that of group B (3.48%) and group C (4.27%), but the difference was not significant (both P>0.05). CONCLUSIONS: Continuous infusion of low dosage of heparin could significantly reduce neurologic impairment score in patients with progressive cerebral infarction, increase cure rate, reduce the recurrence rate, and raise the BI of patients, and it dose not increase the risk of intracranial and extracranial hemorrhage.

[The anti-tumor efforts of thymosin alpha1 on tumor lysate-pulsed dendritic cells in colon cancer in vitro and in vivo].

AIM: To investigate the effects of thymosin alpha1 (Talpha1) on the differentiation, maturation and function of tumor lysate-pulsed dendritic cells (LyDCs) in vitro, and to study the antitumor effects on tumor models of the nude mice bearing colon cancer in vivo. METHODS: Immature DCs (imDCs) were prepared routinely from human peripheral blood mononuclear cells. The LyDCs were prepared from the imDCs loaded with lysate of HT-29 tumor cell line. The phenotypes of imDCs and LyDCs pre- or post-stimulated by Talpha1 were analyzed by flow cytometry. Autologous T cells were cocultured with LyDCs in the presence or absence of Talpha1 2 days later. IL-12 secretion of LyDCs and IFN-gamma secretion of the activated T cells in the supernatants were measured by ELISA. The in vitro cytotoxicity of antigen specific cytotoxic T lymphocytes (CTLs) induced by LyDCs which were treated with Talpha1 was evaluated by MTT assay. A humanized nude mice model bearing colon cancer was established. The in vivo antitumor activity was evaluated in the humanized nude mice after the treatment with LyDCs plus Talpha1 or LyDCs alone. RESULTS: The expression levels of HLA-DR, CD80, CD86 and CD83 in imDCs and LyDCs were markedly up-regulated after the stimulation with Talpha1 respectively (P<0.01). The levels of IL-12 and IFN-gamma were also significantly increased in the presence of Talpha1 (P<0.05 and P<0.01, respectively). Cytotoxicity induced by LyDCs treated with Talpha1 was significantly enhanced (P<0.01) as compared with LyDCs in vitro. The humanized cellular immunity was successfully established in the nude mice model. On the 58 th day after the inoculation of tumor cells, the inhibitory rate of tumor growth was significantly higher in the group treated with LyDCs plus Talpha1 than that in the group treated with LyDCs alone (60.41% and 37.20%, respectively; P<0.01). CONCLUSION: Talpha1 can induce the functional maturation of DCs and enhance the immune response of CD4+Th1 arm and cytotoxicity induced by LyDCs. Talpha1 has a synergistic antitumor effect. It might be a promising adjuvant candidate for DC-based immunotherapy of gastrointestinal carcinomas.