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In recent years, with the development of metabolic reprogramming research, people have changed their understanding of the biological effects of immune cells. Under the stimulation of inflammatory response, immune cells re-regulate their metabolism and bioenergetics, provide energy and substrates for cell survival, and initiate immune effect functions. Nod-like receptor protein 3 (NLRP3) inflammasome, as an important component of the innate immune system, has been shown to sense metabolites such as uric acid and cholesterol crystals, and can be inhibited by metabolites such as ketones. It is also regulated by mitochondrial reactive oxygen species and glycolytic components (such as hexokinase). Recent studies have shown that a variety of metabolic pathways converge as effective regulators of NLRP3 inflammasome. The paper reviews the metabolic regulatory pathways and specificity of NLRP3 inflammasome activation, and its role in renal diseases.
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Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment. As a heterogenous cell population, TAMs usually affect tumor growth, metastasis, and therapeutic resistance. Currently, TAM has attracted wide attention as a promising therapy target for human cancers. As one of the basic treatments of malignant tumors, radiotherapy can regulate the phenotypes and functions of TAM. Meanwhile, TAM can affect the response of cancer cells to radiation. This paper reviews the research advances of TAM in cancer radiotherapy.
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Objective To study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development.Methods In this prospective cohort study,a total of 945 women and their children were included.Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay.Maternal social demographic information was collected by using the a self-administered questionnaire.Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care.Results The differences in newborns' birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroidstimulating hormone,TSH) levels (P＜0.05).Newboms with maternal TSH level ≥P95 or ＜P5 had significantly lower birth length and birth head circumference,compared with the newborns with maternal TSH level between P25-P75 (P＜0.05).Newborns' birth head circumferences showed an inverted U-shaped association with maternal serum TSH level (Y=33.940 + 0.003X-0.109X2,F=4.685,P=0.009).The difference in mental development index (MDI) of the infants at 18-30 months were significant among the infants of mothers with different percentiles of maternal serum TSH level (P＜0.05).Infants with maternal TSH level ≥P90 showed lower MDI (6.39,95％CI:2.29-10.49,P=0.002) compared with the infants with maternal TSH level between P25-P75.Infant's MDI at 18-30 months also showed an inverted U-shaped association with maternal serum TSH level (Y=103.249-1.524X-0.939X2,F=6.616,P=0.001).Conclusions Maternal TSH level was associated with newborn's birth length,birth head circumference and infant's MDI at 18-30 months.Newborn's birth head circumference and infant's MDI at 18-30 months showed an inverted U-shaped association with maternal serum TSH-Z score.
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Objective To study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development.Methods In this prospective cohort study,a total of 945 women and their children were included.Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay.Maternal social demographic information was collected by using the a self-administered questionnaire.Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care.Results The differences in newborns' birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroidstimulating hormone,TSH) levels (P＜0.05).Newboms with maternal TSH level ≥P95 or ＜P5 had significantly lower birth length and birth head circumference,compared with the newborns with maternal TSH level between P25-P75 (P＜0.05).Newborns' birth head circumferences showed an inverted U-shaped association with maternal serum TSH level (Y=33.940 + 0.003X-0.109X2,F=4.685,P=0.009).The difference in mental development index (MDI) of the infants at 18-30 months were significant among the infants of mothers with different percentiles of maternal serum TSH level (P＜0.05).Infants with maternal TSH level ≥P90 showed lower MDI (6.39,95％CI:2.29-10.49,P=0.002) compared with the infants with maternal TSH level between P25-P75.Infant's MDI at 18-30 months also showed an inverted U-shaped association with maternal serum TSH level (Y=103.249-1.524X-0.939X2,F=6.616,P=0.001).Conclusions Maternal TSH level was associated with newborn's birth length,birth head circumference and infant's MDI at 18-30 months.Newborn's birth head circumference and infant's MDI at 18-30 months showed an inverted U-shaped association with maternal serum TSH-Z score.
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Background and purpose:Inlfammatory bowel diseases (IBD) are a group of chronic intestinal diseases, including ulcerative colitis (UC) and Crohn’s disease (CD). This study identified differentially expressed miRNAs in UC, CD and colitis-associated colorectal cancers (CAC) to explore their potential as novel molecular biomarkers. Methods:Tissue samples were taken from 13 UC patients, 3 CD patients, 12 CAC patients, and 8 age-and gender-matched healthy controls. The miRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay. Known targets of deregulated miRNAs were utilized using miRWalk 2.0 database, and subsequent bioinformatics analysis of these target genes was performed by DAVID software (GO-analysis, KEGG-analysis and BIOCARTA-analysis). Results:The data showed that miR-146a, miR-27a, miR-29a, miR-20a and miR-21 were upregulated in UC, CD and CAC tissues compared with normal control. Moreover, the target genes of these miRNAs were enriched in several key signal transduction pathways including cancer-related pathway and immu-nity-associated pathway. Conclusion:miR-146a, miR-27a, miR-29a, miR-20a and miR-21 may play important roles in the switching from IBD to CAC.
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Objective To calculate the maximum ability of the mobile medical team ( MMT) to treat the wounded in order to provide reference for wartime medical support .Methods The flow of casualties between the main units in an MTT is described,data on training is collected through video analysis and questionnaires , the workflow of each unit above is mod-eled by the method of operational research using WINQSB software , and the theoretical maximum value is obtained .Results The theoretical maximum ability of a typical MMT to deal with the wounded is 322 per day when all the function units are operating at full load .Conclusion Under new circumstances , data on an MMT are different from those in the past .Reason-able organization is needed to increase the efficiency while the amount of evacuation should be maximized .
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Objective To construct an executable model of a hypoxia response network (HRN) and to analyze the dynamic evolution mechanism of an HRN including randomness as well as concurrency based on computer simulation. Methods Specific evolution rules and Gillespie algorithm were adoped to study the dynamic evolution of the structural model based on the construction of a structural model of an HRN using stochastic Petri net ( SPN ) .Results Dynamic evolution laws of an HRN were obtained and the simulation results were consistent with laboratory results in response to descript switch-like behavior of an HRN .Conclusion A visualization model of the HRN can be achieved using SPN method.Simulation results achieved by executing the model based on stochastic simulation using specific kinetic parameters can serve as a nice complement to traditional laboratory results , which can help shed light on the structure and function characteristics of an HRN.
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Objective To analyze the process of triage in disaster rescue action performed by a mobile medical unit so that the rescue process can be improved , the efficiency of rescue enhanced , and the decision on health service in rescue action is supported.Methods The process of triage in disaster rescue action was modeled based on stochastic Petri net while the performance of the model was analyzed quantitatively .Results and Conclusion The critical factor which affects the efficiency of rescue work is obtained by analyzing the performance of the model .
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With the great progress in information technology , military medical evacuation has become an extremely important research topic about any information-based war.Thus, this paper aims to analyze the application and effect of modern information technology in military medical evacuation .This paper starts with the developments of modern military medical evacuation and the key areas of military medical evacuation research .Then, the effect of modern information technology on military medical evacuation is discussed regarding the search for and rescue of the wounded , medical treatment of the wounded ,and command and control system of military medical evacuation .Finally, the key technologies for the above tasks are introduced .
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Objective To establisha high altitude military medicine digital library ( HAMMDL) in order to integrate high altitude military medicine ( HAMM ) digital resources and promote transformation of HAMM technology to health service application.Methods The solution of Web 3.0-basedHAMMDL was proposed.Ontology, the metadata and Wiki paradigm were used to manage and present resources , while the Model-View-Controller pattern was used in software design .Results Based on analysis of the functional requirements and key techniques of HAMMDL , design principles were proposed the hierarchical software architecture pattern was designed , the software supporting technology was provided and the construction method of HAMM ontologies was discussed .Conclusion With the synthesized application of relative technologies , smart utilization and socialized content management pattern of HAMM digital resources can be achieved .
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Objective The purpose of this study was to examine the relationship between acute mountain sickness ( AMS) and AMS susceptibility indices before ascent to high altitude and to evaluate their predictive value for AMS. Methods A total of 314 healthy male a-dults were voluntarily enrolled. Their 22 physiological and mental indices of AMS susceptibility were obtained before exposure high altitude. The diagnoses of AMS were based on the Lake Louise score ( LLS) ,an international standard scoring system for AMS. According to the char-acteristics of selected AMS susceptibility indices and the strong fault tolerance of neural network theory, the learning vector quantization ( LVQ) neural network method was adopted to build the prediction model of susceptibility to AMS. Results The results showed the sensitiv-ity of the LVQ model which distinguishes subjects with no-AMS reached 95. 00%,the average correct-prediction precision ultimately reached 72. 22%. The result of prediction is believable. Conclusion The builded LVQ model provide a scientific method for screening crowd who quickly ascend to high altitude,and also can lead to an effective preliminary screening of susceptibility to AMS.
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MicroRNAs (miRNAs) are a type of small non-coding RNAs that are often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma (GC). The expression of miR-638 in GC and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algorithms (TargetScan and miRanda), luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Furthermore, we observed that PLD1 was overexpressed in GC tissues, and high expression of PLD1 in GC predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1.
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Humans , 3' Untranslated Regions , Genetics , Apoptosis , Genetics , Base Sequence , Cell Line, Tumor , Cell Proliferation , Genetics , Down-Regulation , Genetics , MicroRNAs , Genetics , Phospholipase D , Genetics , Prognosis , Stomach Neoplasms , Diagnosis , Genetics , PathologyABSTRACT
OBJECTIVE:To provide reference for health service support at high altitude area. METHODS:375 servicemen who rapidly entered high altitude area were investigated by questionnaire in 2013 to investigate the compliance of using high alti-tude special medicines and incidence of mountain sickness and analyze its correlation. RESULTS:375 questionnaires were distribut-ed and 324 questionnaires were collected with effective response rate of 86.4%. The utilization rate of Multivitamin tablet,Skin cream and Lip balm for high altitude area were 30.9%,13.3% and 40.1% respectively. The compliance of using high altitude spe-cial medicines had effect on the incidence of related mountain sickness. The incidence of mountain sickness of people who followed the physician’s instructions was significantly lower than those who did not. The difference was statistically significant(P<0.05). CONCLUSIONS:High altitude special medicines can relieve and prevent the mountain sickness. But the overall compliance of us-ing high altitude special medicines was not ideal. The education of high altitude special medicines should be strengthened,and dos-age forms and medicine instruction should be enhanced to improve its compliance and play better protective effect.
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MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.
Subject(s)
Animals , Female , Humans , Male , Middle Aged , Base Sequence , Cell Line, Tumor , Cell Movement , Genetics , Colorectal Neoplasms , Genetics , Pathology , Therapeutics , Down-Regulation , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , HCT116 Cells , HEK293 Cells , Mice, Inbred BALB C , Mice, Nude , MicroRNAs , Genetics , Neoplasm Invasiveness , RNA Interference , Receptor, Notch1 , Genetics , Metabolism , Receptors, Autocrine Motility Factor , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid , Survival Analysis , Xenograft Model Antitumor AssaysABSTRACT
Objective To establish a high-performance liquid chromatography (HPLC) method with diode array detection to simultaneously determine carbamazepine,phenytoin,and phenobarbital in serum.Methods Extraction solvent (800μl ethylene acetate) and sample (0.2 ml) was mixed,extracted for 2 min,and centrifuged (3500 r/min,4 minutes).A volume (600 μl) of extract liquor was volatilized to dryness in water bath with the volatilization temperature 75 ℃,then was redissolved with 1.0 ml mobile phase.Analysis conditions was column temperature 30°,mobile phase (methanol∶ water =40∶60),and detection wavelength of 254 nm.Three metabolites were effectively separated.Results Under the optimized condition,calibration curves of three metabolites were linear in the ranges of (1.52 ～ 120 mg/L) and the correlation coefficients were not less than 0.999.The detection limits (S/N =3) were in the range of 0.4 ～ 1.5 mg/L.The spiked recoveries were in the range of 91.3％ ～ 111％ with relative standard deviations (RSD) less than 5％.Conclusions The optimal pretreatment condition for the sample was established.The chromatographic separation and the detection condition were optimized.The method was sensitive and accurate,and could meet the need of monitoring serum drug concentration.
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Objective To approach the selection of appropriate period and mode of blood purification for treatment of patients with severe acute pancreatitis(SAP)based on acute physiology and chronic health evaluationⅡ(APACHEⅡ)score. Methods The clinical data of 89 patients with SAP were retrospectively analyzed. They were assigned into two groups:the hemoperfusion(HP)and short continuous veno-venous hemodiafiltration(SCVVHDF) group(HP+SCVVHDF,49 cases)and the HP and hemodiafiltration(HDF)group(HP+HDF,40 cases). All the patients were evaluated by APACHEⅡscore. In the HP+HDF group,26 cases with APACHEⅡ0.05),while the APACHEⅡ score,PaO2/FiO2,CRP, SCr and ALT were improved more significantly in group C than those in group B(P<0.05 or P<0.01). The mortality rate of those SAP patients with APACHEⅡscore<15 was lower than those in cases with APACHEⅡscore 15-20〔6.82%(3/44)vs. 24.44%(11/45),P<0.05〕. Conclusions Blood purification is an effective measure to save patients with SAP. The APACHEⅡ score used to select the mode of blood purification in appropriate period for treatment of SAP has guiding significance. Currently the modes of blood purification have limited value and cannot cure all SAP patients.
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Evaluation of medical assistance capability plays a significant role in improving medical assistance capability and accomplishing a diverse array of military tasks.Based on gray theory and fuzzy mathematics,we put forward a new evaluation model for disaster medical assistance capability,integrating the AHP,the gray cluster analysis and fuzzy evaluation.This model not only reflects the ambiguity of medical assistance capability evaluation but also makes full use of the information,which avoids the flaws caused by single method of fuzzy mathematics.It provides a new way to evaluate disaster medical assistance capability comprehensively and systematically.
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Objective To investigate the association of promoter hypermethylation of secreted frizzled-related proteins (SFRPs) in patients with colorectal cancer. Methods The promoter hypermethylation of SFRPs in 20 sporadic colorectal cancer tissues and adjacent mucosa were detected by methylation-specific PCR. The amplified DNA was subcloned into the T-A cloning vector and sequenced. Two colorectal cancer cell lines (HCT116 and SW480) were treated with 5-aza-2' deoxycytidine for demethylation. The promoter hypermethylation and protein expression of SFRPs in colorectal cancer cell lines were detected by methylation-specific PCR and Western blotting. Results It was demonstrated that the hypermethylation of SFRP 1, 2, 4 or 5 was 19/20,17/20,3/20 or 13/20in cancer tissues, respectively, whereas it was 12/20, 8/12, 1/20 or 7/20 in adjacent mucosa,respectively. SFRP 1, 2 or 5 methylation was more frequently found in cancer tissue than in adjacent mucosa (P～0.05). Methylation of SFRP 1, 2, 4 and 5 were found in HCT116 cell line, but only SFRP1 and SFRP2 were found in SW480 cell line. There was a negative correlation between protein expression and methylation of SFRPs. The Western blotting revealed that SFRP protein re-expressedafter it treated with 5-aza-2' deoxyeytidine. Conclusion Methylation of SFRP 1, 2 or 5 gene is associated with the evolution of eolorectal cancer, and is closely related to silencing expression.
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Objective To explore the value of interphase fluorescence in situ hybridization(FISH) in the detection of trisomy 8 in patients with hematologic disorders. Methods Seventy-seven patients were vestigated by directly labeled centrome DNA probes specific for 8 chromosome. The results were compared with that of conventional cytogenetic (CC) analysis. Results The proportion of trisomy 8 of 77 cases of hematologic disorders detected by FISH is higher than by G-banding karyotyping and FISH could offer the result when conventional cytogenetic methods failed to diagnose. Conclusion Interphase FISH is more sensitive in the detection of trisomy 8 than CC, and FISH displays its superiority in the detection of small clone.
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Objective To investigate the mechanism of renal damage due to rupture of atheroselerotic plaque of renal artery in apolipoprotein E (ApoE) knock-out mice. Methods The model for atherosclerotie renal artery stenosis (ARAS) was established by using ApoE knockout mice. The model mice with renal artery stenosis <50% were divided into the plaque rupture group and the non-plaque rupture group. Wild-type C57BL/6J mice were used as the control group. All the mice were raised under the same conditions. The renal arteries and kidneys were collected for the following analysis. Nuclear factor-kappa-Bp65 (NF-kBp65), intercellular adhesion molecule 1 (ICAM-1) and P-selectin (P-sel) were determined by Western blotting. The expression of interleukin 6 (IL-6) mRNA was detected by RT-PCR. Immunohistochemistry was performed by using serial sections to detect F4/80-related macrophages. Urine n-acetyl-β-d-glucosaminidase (NAG) activity was determined by direct enzyme-substrate coloration. Results In comparison with the nonplaque rupture group and the control group, the expression of NF-kBp65 protein in the blood, renal artery and kidney increased significantly in the plaque rupture group (P<0.05). The expression of F4/80, ICAM-1, P-sel, and IL-6 mRNA were increased significantly in the plaque rupture group (P<0.05), as compared with the non-plaque rupture group and the control group. The Ser and the activity of urine NAG in the plaque rupture group were higher than those in the non-plaque rapture group. The expression of NF-KBp65 protein differed insignificantly between the control group and the non-plaque rupture group (P>O.05). The group differences in the expression of F4/80, ICAM-1, P-sel, and IL-6 mRNA were similar to those in the expression of NF-KBp65 protein. The group differences in the activity of urine NAG and the Scr were similar to those in the expression of NF-kBp65 protein. Conclusion Rupture of atherosclerotic plaque of renal artery causes renal pathology change and renal function damage, which is mediated by inflammation.