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Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.
Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.
Subject(s)
Humans , Heart Failure/drug therapy , Prognosis , Stroke Volume , Ventricular Function, Left , Heart VentriclesABSTRACT
ABSTRACT Background: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. Objective: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. Methods: We established chronic inflammatory pain model in rats through a single injection of Complete Freund's Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund's Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. Results: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund's Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund's Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. Conclusion: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.
RESUMO Introdução: A acupuntura tem sido amplamente utilizada para alívio de dor. No entanto, seus mecanismos são muito pouco conhecidos. Objetivo: Investigar a relação entre o efeito analgésico da eletroacupuntura e a regulação da expressão de adenosina e de substância P. Métodos: Utilizou-se um modelo de dor inflamatória crônica em ratos por injeção única do Adjuvante Completo de Freund e, em seguida, os animais foram tratados com eletroacupuntura diariamente. Foram aplicadas sete sessões bilaterais de eletroacupuntura (ST36 e BL60, 0,5 a 1,5 mA, força inicial de 0,5 mA, aumentada em 0,5 mA a cada 10 minutos, 30 minutos por sessão, uma sessão por dia) em ratos com Adjuvante Completo de Freund, por sete dias. O efeito analgésico da eletroacupuntura foi avaliado pela medida do limiar de retirada da pata em ratos que receberam estimulações mecânica e térmica. Resultados: A estimulação diária com eletroacupuntura aumentou efetivamente o limiar de retirada da pata em ratos com Adjuvante Completo de Freund. A eletroacupuntura aumentou o nível de adenosina na região zusanli. Estudos posteriores mostraram que a eletroacupuntura poderia diminuir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alpha, interleucina-1β, interleucina-6 e CD68 nos gânglios da raiz dorsal. Curiosamente, a injeção direta de antagonistas do receptor de adenosina A1 ou de substância P, ou a transecção da raiz do nervo dorsal, podem prejudicar significativamente as ações analgésicas induzidas pela eletroacupuntura em ratos com Adjuvante Completo de Freund e reduzir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alfa, interleucina-1β, interleucina-6 e CD68. Por fim, confirmamos que a injeção direta de um agonista do receptor da adenosina A1 reproduziu os efeitos analgésicos da eletroacupuntura. Conclusão: Nossos resultados indicam a regulação da secreção da substância P mediada pela adenosina. A via mediada pela substância P pode estar envolvida no processo de analgesia por eletroacupuntura em ratos.
Subject(s)
Animals , Rats , Substance P/chemistry , Electroacupuncture , Adenosine/chemistry , Pain , Rats, Sprague-DawleyABSTRACT
To compare the therapeutic effects of different treatment methods on the nude mice bearing colon cancer HT29 cells. BalB/C nude mice colon cancer stem cell models were established and randomly divided into the following four groups, with 8 nude mice in each group: blank control group, DC-CIK group, Huaier group, and Huaier combined with DC-CIK group (combined treatment group). The mice in DC-CIK group and combined treatment group received 1×10⁶ DC-CIK cells treatment by tail vein injectionafter the tumor stem cells were inoculated for 4 days,2 times a week for three weeks. The mice in Huaier group and combined treatment group received intragastric administration at the dose of 20 g/60 kg body weight, 0.2 mL/time, once a day for a total of three weeks. The mice in control group received equal volume of normal saline. Tumor size and body weight of nude mice were measured every 2 days during treatment for three weeks in each group. After the treatment, the nude mice were sacrificed to measure the tumor weight and the tumor inhibition rate was calculated. The RT-PCR method was used to detect the expression levels of the key genes in the signal pathway. After the end of the treatment, the quality of the tumor in the Huaier group, DC-CIK group and combined treatment group was significantly lower than that in the control group; the quality in combined treatment group was significantly lower than that in Huaier group and DC-CIK group.Among them, the tumor inhibition rate reached 46.77% in the combined treatment group. In respect of changes in expression levels of key genes in the signaling pathway, the mRNA expression levels of key genes PI3KR1 and Akt in PI3K/Akt pathway, key genes Wnt1 and CTTNB1 in Wnt/-catenin pathway, and key genes Notch1, Notch2, Notch3 in Notch pathway in the combined treatment group were lower than those in DC-CIK group and Huaier group. The Huaier combined with DC-CIK group showed best therapeutic effect among different treatment methods for HT29 stemcell colon tumors in nude mice, providing a new idea for clinical treatment of colon cancer.
Subject(s)
Animals , Humans , Mice , Cell Line, Tumor , Colonic Neoplasms , Drug Therapy , Complex Mixtures , Pharmacology , Mice, Inbred BALB C , Mice, Nude , Neoplastic Stem Cells , Signal TransductionABSTRACT
<p><b>BACKGROUND</b>Lymphocyte subsets play important roles in rejection in liver transplant recipients, and the effect of splenic function on these roles remains unknown. The aim of this study was to explore the feasibility to adjust immunosuppressive agents based on splenic function status through detecting the lymphocyte subsets in liver transplantBeijing recipients.</p><p><b>METHODS</b>The lymphocyte subsets of 49 liver transplant recipients were assessed in the 309th Hospital of Chinese People's Liberation Army between June 2014 and August 2015. The patients were divided into splenectomy group (n = 9), normal splenic function group (n = 24), and hypersplenism group (n = 16). The percentages and counts of CD4+ T, CD8+ T, natural killer (NK) cell, B-cell, regulatory B-cell (Breg), and regulatory T-cell (Treg) were detected by flow cytometer. In addition, the immunosuppressive agents, histories of rejection and infection, and postoperative time of the patients were compared among the three groups.</p><p><b>RESULTS</b>There was no significant difference of clinical characteristics among the three groups. The percentage of CD19+CD24+CD38+ Breg was significantly higher in hypersplenism group than normal splenic function group and splenectomy group (3.29 ± 0.97% vs. 2.12 ± 1.08% and 1.90 ± 0.99%, P = 0.001). The same result was found in CD4+CD25+FoxP3+ Treg percentage (0.97 ± 0.39% vs. 0.54 ± 0.31% and 0.56 ± 0.28%, P = 0.001). The counts of CD8+ T-cell, CD4+ T-cell, and NK cell were significantly lower in hypersplenism group than normal splenic function group (254.25 ± 149.08 vs. 476.96 ± 225.52, P= 0.002; 301.69 ± 154.39 vs. 532.50 ± 194.42, P= 0.000; and 88.56 ± 63.15 vs. 188.33 ± 134.51, P = 0.048). Moreover, the counts of CD4+ T-cell and NK cell were significantly lower in hypersplenism group than splenectomy group (301.69 ± 154.39 vs. 491.89 ± 132.31, P= 0.033; and 88.56 ± 63.15 vs. 226.00 ± 168.85, P = 0.032).</p><p><b>CONCLUSION</b>Splenic function status might affect the immunity of liver transplant recipients, that should be considered when we make immunosuppressive protocols.</p>
Subject(s)
Female , Humans , Male , Middle Aged , CD4-Positive T-Lymphocytes , Allergy and Immunology , Hypersplenism , Allergy and Immunology , Immunosuppressive Agents , Therapeutic Uses , Killer Cells, Natural , Allergy and Immunology , Liver Transplantation , Methods , Lymphocyte Subsets , Allergy and Immunology , Retrospective Studies , Sirolimus , Therapeutic Uses , Spleen , Allergy and Immunology , T-Lymphocytes, Regulatory , Allergy and ImmunologyABSTRACT
Objective To investigate the effect of sirolimus (SRL)-based immunosuppression regimen on the survival and tumor recurrence in liver transplantation recipients with hepatocellular carcinoma beyond the standard Milan criteria. Methods We retrospectively analyzed 22 patients who received liver transplant in our hospital for HCC beyond the standard Milan criteria from June 2010 to June 2011. Eleven patients received tacrolimus for immunosuppression after liver transplant and the other 11 were converted from tacrolimus to SRL-based immunosuppression. The incidence rate of acute rejection, tumor-free survival period, blood routine, liver function and complications were compared between the two groups. Results The incidence rates of acute rejection were not significantly different between the two groups after a mean follow-up of (12 + 3) months (range, 7-18 months). Four patients in the SRL group and eight patients in tacrolimus group had HCC recurrence and metastasis. Kaplan-Meier recurrence-free survival curves demonstrated that SRL group had a significantly longer HCC recurrence-free survival than tacrolimus group(P<0. 05). Compared with tacrolimus group, SRL group had significantly lower leukocyte and platelet counts (P<0. 05). The tacrolimus-related nephrotoxicity was modestly improved in all the three patients after converted to SRL. Two patients suffered oral ulcers after conversion to SRL treatment and no severe complications such as arterial thrombosis were observed. Conclusion SRL can be effectively used for liver transplant recipients with hepatocellular carcinoma beyond the standard Milan criteria; it can achieve a similar anti-rejection effect to tacrolimus and can greatly reduce tumor recurrence.
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The myeloid differentiation primary response protein 88 (Myd88) is an essential adaptor protein, which mediates in all Toll-like receptor (TLR) members signal transduction, except for TLR3. In this study, the 4464 bp genomic sequence of porcine Myd88 was first isolated, whereupon tissue distribution, chromosome mapping and single nucleotide polymorphism (SNP) were analyzed. Our results revealed that porcine Myd88 gene, which was located at chromosome 13 linked with marker S0288 (distance = 40 cR; LOD = 8.66), was widely expressed in all the examined tissues. There were 16 potential SNPs in the isolated genome fragment. SNP 797T/C in the first intron was studied, with no significant association being found between the genotype and immune traits in pigs (p > 0.05). The porcine Myd88 protein contained both the death domain (DD) and the Toll/IL-1 receptor domain (TIR). Leu residues, essential for its structure, were the most abundant encountered in the DD. The TIR contained two conserved motifs which may play important roles in the Myd88 function.
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<p><b>OBJECTIVE</b>To explore the effects of aberrant expression of sperm protein 17 (Sp17) on the migration of the ovarian cancer cell line HO-8910.</p><p><b>METHODS</b>The recombinant plasmid pEGFP-Sp17 containing Sp17 and enhanced green fluorescent protein gene was transfected into the human ovarian cancer cell line HO-8910 with Lipofectamine 2000. The expression of Sp17 was examined by RT-PCR and Western blot, and the cell migratory capability detected by Transwell chamber assays.</p><p><b>RESULTS</b>Sp17 was expressed as a fusion protein with EGFP after transfected. There was a significant difference in the migratory cell number of the transfected and the control cells (156.6 +/- 14.9/HP vs 39.3 +/- 8.53/HP, P < 0.05).</p><p><b>CONCLUSION</b>The aberrant expression of Sp17 greatly enhances the migration of ovarian cancer cells.</p>
Subject(s)
Female , Humans , Male , Antigens, Neoplasm , Genetics , Antigens, Surface , Genetics , Biomarkers, Tumor , Genetics , Carrier Proteins , Genetics , Cell Line, Tumor , Cell Movement , Gene Expression Regulation, Neoplastic , Ovarian Neoplasms , Metabolism , Pathology , TransfectionABSTRACT
As the new type cornea ulcer renovation material, the biological amnion is to be implanted into the human body for a long time, a subchronic toxicity study in rats is made to evaluate its possibility of subchronic toxicity. The study is based on the requirements of "Biological Evaluation of Medical Devices, Part 11: Tests for systemic toxicity and Part 6: Tests for local effects after implantation". After the implantation of examples to be tested, animals were observed daily for mortality and 92 days later the possible subchronic toxicity was evaluated. And a necropsy was conducted and the selected organs were excised, weighed, and processed histologically. Body weights, organ weights, organ/body weight ratios, hematology values and clinical chemistry values were analyzed statistically. Results show that daily clinical observation, body weights, necropsy findings, organ weights and organ/body weight ratios were within acceptable limits in test and control treatment groups. There were no obvious changes in histopathology, hematology values or clinical chemistry values in either male or female rats and no notable differences between the biological amnion and the control amnion. This study proves that, the cornea ulcer renovation material, the biological amnion does not induce subchronic toxicity.
Subject(s)
Animals , Female , Male , Rats , Amnion , Transplantation , Biological Products , Toxicity , Corneal Ulcer , General Surgery , Materials Testing , Rats, Wistar , Toxicity Tests, SubchronicABSTRACT
Objective To study the protective role of AngiotensinⅡreceptor inhibitor in ventilator-induced lung injury of rats.Method Forty healthy male SD rats were equally divided into four group (A,B,C,D group,n=10).Group A served as control group,group B had low tidal volume (V_T=10 ml/kg) with breathing rate (P)=80/min;group C had high tidal volume (V_T=40 ml/kg) group with breathing rate 80/min;group D had high tidal volume (V_T=40 ml/kg) group with breathing rate 80/min,all rats in group D were pretreated with Losartan.The duration of ventilation in 'all groups was two hours.Rats were sacrificed after experiment finished. The lung lavage liquid and lung tissue were collected and preserved with well established methods.Lung pathological change was observed by microscope;lung cell apoptosis was assessed with TUNEL;the expression of ANGⅡwas assayed with RT-PCR.The measured variables also included total protein,WBC,W/D,MPO. Results In comparison with B group,all variables in group C were significantly increased (P