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1.
J Environ Manage ; 355: 120311, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432007

RESUMO

Variable renewable energy (VRE) is the most promising form of primary generation under a carbon neutrality target due to its environmental benefits, incentive policy, and technological progress. However, the increasing proportion of VRE generation, such as solar and wind power, has sharply increased integration cost and reduced power grid stability. This study uses portfolio theory to investigate China's optimal power generation portfolio by 2050 considering flexibility constraint and system cost, including technical and integration costs. The results demonstrate that non-fossil-fuel power generation technologies have cost and emission reduction advantages over fossil-fuel-based technologies. VRE generation technologies must be developed in synergy with other forms of power generation when considering flexibility requirement and integration cost. A complete phase-out of fossil-fuel power generation technologies in China appears unlikely in the study period. Gas-fired and coal-fired power generation are the pillar forms of power generation to meet future flexibility needs.


Assuntos
Carbono , Combustíveis Fósseis , Carbono/análise , Carvão Mineral , Vento , China , Dióxido de Carbono/análise , Centrais Elétricas
2.
Mol Neurobiol ; 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097915

RESUMO

Depression poses a significant threat to global physical and mental health, impacting around 3.8% of the population with a rising incidence. Current treatment options primarily involve medication and psychological support, yet their effectiveness remains limited, contributing to high relapse rates. There is an urgent need for innovative and more efficacious treatment modalities. Stem cell therapy, a promising avenue in regenerative medicine for a spectrum of neurodegenerative conditions, has recently garnered attention for its potential application in depression. While much of this work remains preclinical, it has demonstrated considerable promise. Identified mechanisms underlying the antidepressant effects of stem cell therapy encompass the stimulation of neurotrophic factors, immune function modulation, and augmented monoamine levels. Nonetheless, these pathways and other undiscovered mechanisms necessitate further investigation. Depression fundamentally manifests as a neurodegenerative disorder. Given stem cell therapy's success in addressing a range of neurodegenerative pathologies, it opens the door to explore its application in depression treatment. This exploration may include repairing damaged nerves directly or indirectly and inhibiting neurotoxicity. Nevertheless, significant challenges must be overcome before stem cell therapies can be applied clinically. Successful resolution of these issues will ultimately determine the feasibility of incorporating stem cell therapies into the clinical landscape. This narrative review provides insights into the progress of research, potential avenues for exploration, and the prevailing challenges in the implementation of stem cell therapy for treatment of depression.

3.
Adv Sci (Weinh) ; 10(36): e2303457, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37983567

RESUMO

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.


Assuntos
Colite Ulcerativa , Colite , Humanos , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Células Th17/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Células Epiteliais/metabolismo , Tretinoína/metabolismo , Tretinoína/farmacologia , Tretinoína/uso terapêutico
4.
Sci Rep ; 13(1): 14744, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679399

RESUMO

Patients narratives are being recorded increasingly frequently and spontaneously in short user produced content (UGC) films, which may have an impact on the vlogger's health as well as the public's comprehension of the relevant health concerns. This paper addressed three research questions regarding the population characteristics of UGC video publishers, the narrative theme of the videos, and the emotional orientation of the commenters. This study aimed to deepen our understanding of COVID-19 patients' narrative intentions and emotional needs through the theoretical frameworks of theory of planned behavior (TPB) and negative dominance theory (NDT). We collected 335 videos from 28 COVID-19 patients and 572,052 comments as samples on Douyin platform, the largest short-video website in China. Using Latent Semantic Analysis, we analyzed the descriptive information of the video blogs, the narrative textual information of the videos, and the emotional orientation of the comments. Our findings revealled seven categories of narrative themes, with 52.1% of video comments exhibiting a positive emotional orientation. Within a framework integrating TPB and NDT theories, we analyzed the behavioral intentions of vloggers and viewers during COVID-19 epidemic, and interpreted the persistent posting of videos and the active posting of comments as positive actions that counteracted the multiple effects of negative messages. This study contributes to the understanding of individual narratives in macro-risk communication, both theoretically and empirically, and offers policy recommendations in relevant fields.


Assuntos
COVID-19 , Humanos , Narração , Comunicação , Blogging , China/epidemiologia
5.
Virol J ; 20(1): 114, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280711

RESUMO

BACKGROUND: COVID-19 infection continues all over the world, causing serious physical and psychological impacts to patients. Patients with COVID-19 infection suffer from various negative emotional experiences such as anxiety, depression, mania, and alienation, which seriously affect their normal life and is detrimental to the prognosis. Our study is aimed to investigate the effect of psychological capital on alienation among patients with COVID-19 and the mediating role of social support in this relationship. METHODS: The data were collected in China by the convenient sampling. A sample of 259 COVID-19 patients completed the psychological capital, social support and social alienation scale and the structural equation model was adopted to verify the research hypotheses. RESULTS: Psychological capital was significantly and negatively related to the COVID-19 patients' social alienation (p < .01). And social support partially mediated the correlation between psychological capital and patients' social alienation (p < .01). CONCLUSION: Psychological capital is critical to predicting COVID-19 patients' social alienation. Social support plays an intermediary role and explains how psychological capital alleviates the sense of social alienation among patients with COVID-19 infection.


Assuntos
COVID-19 , Capital Social , Isolamento Social , Apoio Social , COVID-19/psicologia , Humanos , China , Análise de Mediação , Modelos Psicológicos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Intervalos de Confiança
7.
Signal Transduct Target Ther ; 8(1): 46, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717539

RESUMO

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.


Assuntos
COVID-19 , Humanos , Adulto , SARS-CoV-2 , Interleucina-8 , Citocinas
8.
BMC Cancer ; 21(1): 531, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971846

RESUMO

BACKGROUND: Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer. METHODS: We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan-Meier method was used to assess the PFS. RESULTS: Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25-39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P < 0.001). A novel discovery of our study was to verify the prognostic values of retrieved lymph nodes count combining with FIGO staging system, which had never been investigated in cervical cancer before. According to the Kaplan-Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis, significant improvements were found after the combination of retrieved lymph nodes count and FIGO stage in predicting PFS for cervical cancer patients (P < 0.001, AUC = 0.826, 95% CI: 0.689-0.962). CONCLUSION: Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.


Assuntos
Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
9.
Signal Transduct Target Ther ; 5(1): 283, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277466

RESUMO

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.


Assuntos
Basigina/genética , COVID-19/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Basigina/imunologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Pandemias , Ligação Proteica/imunologia , Domínios Proteicos/genética , Domínios Proteicos/imunologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética , Internalização do Vírus
10.
J Gynecol Obstet Hum Reprod ; 47(9): 461-468, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30142473

RESUMO

There is strong evidence indicating that smoking has negative effects on female reproductive health. Studies to investigate the effects of female smoking on IVF outcomes have been conducted by several research groups, yet the results are controversial. To evaluate the impacts of female smoking on the outcomes of assisted reproduction, a meta-analysis was performed, which included studies published in English up to September 6, 2017 from the MEDLINE, EMBASE, and Cochrane library databases. Twenty-eight studies encompassing 5009 female smokers seeking assisted reproduction and 10,078 non-smokers were used in this meta-analysis. Significant negative outcomes were detected in the female smokers compared with non-smokers including decreases in live birth rate per cycle (OR=0.52, 95% CI 0.37-0.74), in clinical pregnancy rate per cycle (OR 0.59, 95% CI 0.51-0.68), in number of retrieved oocytes (MD=-0.87, 95% CI -1.39 to -0.25), and in average fertilization rate (MD=-4.80, 95% CI -8.49 to -2.02), as well as a significantly increased miscarriage rate per pregnancy (OR=2.48, 95% CI 1.79-3.43). In conclusion, the current meta-analysis provides compelling evidence that female smoking has a significantly negative impact on the outcomes of assisted reproductive technology (ART) and strongly recommends that female smokers will greatly benefit from a smoking cessation before employing ART to become pregnant.


Assuntos
Aborto Espontâneo/epidemiologia , Fumar Cigarros/epidemiologia , Nascido Vivo/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Resultado da Gravidez/epidemiologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Fumar Cigarros/efeitos adversos , Feminino , Humanos , Gravidez
11.
Mol Med Rep ; 18(4): 3563-3568, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106107

RESUMO

Ghrelin has a protective function in the nervous system, including anti­inflammatory and antiapoptotic. The objective of the present study was to examine the anti­inflammatory effects of the ghrelin on nuclear factor­κB (NF­κB) and tumor necrosis factor­α (TNF­α) gene and protein expression in an epileptic seizure model. Epileptic seizures were induced in healthy male Wistar rats (~3 weeks old) with 300 mg/kg pilocarpine, and brains from rats with Racine stage IV or V seizures were investigated further in the present study. The effect of ghrelin treatment on TNF­α and NF­κB protein and mRNA expression was assessed by immunohistochemistry and semi­quantitative reverse transcription polymerase chain reaction, respectively. TNF­α and NF­κB protein and mRNA expression were significantly increased in the pilocarpine and the pilocarpine + saline groups compared with the control group. Ghrelin intervention significantly decreased TNF­α and NF­κB protein and mRNA expression compared with the pilocarpine and the pilocarpine + saline groups, although it did not reduce expression levels to those seen in the normal control group. Ghrelin reduces inflammation in cortical neurons following epileptic seizure, and therefore may reduce necrosis and the loss of nerve cells, preserving the normal function of the cortex. Ghrelin may alleviate cortex inflammation reaction by adjusting the TNF­α and NF­κB so as to reduce child epilepsy attack repeatedly. The findings of the present study may contribute to the clarification of the role of Ghrelin in the brain in seizure­induced immune system physiology and may also present novel approaches to the etiology and treatment of epileptic seizures.


Assuntos
Anti-Inflamatórios/uso terapêutico , Córtex Cerebral/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Grelina/uso terapêutico , Inflamação/tratamento farmacológico , NF-kappa B/genética , Fator de Necrose Tumoral alfa/genética , Animais , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Epilepsia/induzido quimicamente , Epilepsia/genética , Epilepsia/patologia , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Masculino , NF-kappa B/análise , Pilocarpina , Ratos Wistar , Fator de Necrose Tumoral alfa/análise
12.
Eur Spine J ; 24(9): 2056-64, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25895882

RESUMO

PURPOSE: To report our 11-year minimum clinical and radiological outcomes, as well as complications of the Charite III total disc replacement (TDR). METHODS: A total of 35 patients indicated for total disc replacement were implanted with the Charite III prosthesis. Clinical evaluation included visual analog scale (VAS) for back pain and the Oswestry disability index (ODI). Radiological parameters of intervertebral disc height (IDH), range of motion (ROM), lumbar lordosis, lumbar scoliosis and prosthesis position were evaluated. Complications and reoperation rates were also assessed. RESULTS: Thirty-two patients had a minimum 11-year follow-up, and 33 prostheses were implanted. The mean follow-up time was 11.8 years, ranging from 11.3 to 13.8 years. Twenty-eight patients (87.5 %) had a successful outcome, as defined by the FDA. Reoperation was performed in 2 patients for adjacent segment degeneration and pedicle fracture (1 case each). Both VAS and ODI scores showed significant improvement compared to baseline. At the final follow-up, the ROM of both the index- and adjacent-level showed an obvious decrease. The IDH of the index level showed a tendency to decrease, but the difference was not significant. The IDH of adjacent levels were not significantly affected by the surgery. Mean lumbar lordosis was increased at the final follow-up, and lumbar scoliosis over 3° was observed in 12 patients (37.5%), with a mean angle of 5.6° (range 3°-12°). Of all 35 prostheses, 15 were left-shifted, 3 were right-shifted and 14 were just in the middle. In the coronal plane, 25 were rated as ideally placed, 5 were discretely shifted, 4 were slightly shifted and 1 was markedly shifted. In the sagittal plane, only 12 prostheses were rated as ideally placed, 14 were discretely shifted and 9 were suboptimally placed. Prosthesis subsidence was noted in 3 (9.4%) patients (the subsidence distances were 3.1, 4.2 and 2.8 mm, respectively). Heterotopic ossification was detected in 25 segments (71.4%), consisting of Class-I heterotopic ossification in 7 segments (20.0%), Class-II in 9 segments (25.7%), and Class-III in 9 segments (25.7%). Class-IV heterotopic ossification was not observed. CONCLUSION: The cumulative survival was 100% at a mean follow-up of 11.8 years. Clinical and radiological results were satisfactory and long-term clinical results were maintained for a mean follow-up of 11.8 years. Reoperation and complication rates are acceptable, and our study does not substantiate the fear of reoperation or late complications. The results of our long-term follow-up indicate that, with strict indication, TDR is a safe and effective procedure as an alternative to lumbar fusion.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Disco Intervertebral/cirurgia , Prótese Articular , Vértebras Lombares/cirurgia , Substituição Total de Disco/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Reoperação , Resultado do Tratamento
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(2): 298-302, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21518475

RESUMO

This study was aimed to investigate the expression and clinical significance of CDX1, CDX2 and CDX4 genes in acute lymphocytic leukemia (ALL). Expressions of CDX1, CDX2, and CDX4 in 51 adult acute lymphocytic leukemia patients and 14 healthy subjects were detected by reverse transcription polymerase chain reaction (RT-PCR). The results indicated that CDX1, CDX2 and CDX4 were not expressed in 14 healthy persons and 15 CR ALL patients, the positive expression rate of CDX2 gene in de novo ALL patients was 60.8%, while it obviously decreased in patients with complete remission (CR) (p < 0.05); the expression of CDX2 was increased again in relapsed patients (81.8%). When the expression of CDX2 was analyzed in different risk groups of ALL patients, the CDX2 expression rate in high risk (HR) patients was 91.7%, and that in the standard risk (SR) group was 45.7%. Furthermore, analyses of CDX1 and CDX4 expression in series of ALL samples did not show the expression of these genes. In patients with adult ALL at diagnosis and relapse, the CR rate of patients with CDX2 positive expression was lower than that of patients with CDX2 negative expression (p < 0.05). The median survival time in CDX2 positive expression patients was shorter than that in negative expression patient. It is concluded that expression of CDX2 may correlated with pathogenesis and relapse of adult ALL, but the expression of CDX1 and CDX4 don' t associated with pathogenesis and relapse of adult ALL; the CR rate and prognosis of patients with CDX2 positive expression is lower and poor. The expression of CDX2 may be used as a marker for occurrence, relapse and poor prognosis of adult ALL patients.


Assuntos
Genes Homeobox , Proteínas de Homeodomínio/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Fator de Transcrição CDX2 , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Zhonghua Wai Ke Za Zhi ; 46(5): 342-5, 2008 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-18785528

RESUMO

OBJECTIVE: To evaluate the clinical and radiographic results of total lumbar disc replacement with SB Charité III prosthesis. METHODS: From Dec 1999 to Dec 2006, total lumbar disc replacement with SB Charité III prosthesis was performed in 65 patients affected with degenerative lumbar disc disorders. Among these patients, 48 (52 prosthesis) were followed up for more than two years (from 2.0 to 7.5 years). There were 22 males and 26 females with an average age of 43 years old (from 36 to 58 years). The diagnosis was lumbar disc herniation with low back pain in 34 patients, discogenic low back pain in 9 patients and failed lumbar disc surgery in 5 patients. All patients underwent standard anterior procedure under general anesthesia. One level replacement was done in 44 patients (L3,4 in 3, L4,5 in 23 and L5-S1 in 18), and two level procedures in 4 patients (L3,4/L4,5 in 1 and L4,5/L5-S1 in 3). Clinical and radiographic results of these patients were evaluated at each follow-up time (1, 3, 6, 12, 24 months after operation and the latest). RESULTS: The average visual analogue scales score for pain was 9.3 before operation, changed to 4.3 one month after operation, further declined to 2.6 two years after operation and finally to 1.8 at the latest follow-up evaluation. Meanwhile, the average Oswestry Disability Index was 45.8 before operation, 28.6 one month after operation, 12.5 two years after operation and 8.2 at the latest followup evaluation. All operated levels but one maintained mobile and there was no significant loss of range of motion observed. Complications such as implant dislocation or significant subsidence of the prosthesis occurred in none case of this group. All patients but one (98%) were satisfied with the surgery at the latest follow-up evaluation. CONCLUSIONS: Total lumbar disc replacement is an effective method for the treatment of degenerative disc disorders. Its long-term outcome remains to be verified.


Assuntos
Artroplastia de Substituição , Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
Zhonghua Yi Xue Za Zhi ; 85(28): 1987-90, 2005 Jul 27.
Artigo em Chinês | MEDLINE | ID: mdl-16313778

RESUMO

OBJECTIVE: To investigate the effect of exogenous carbon monoxide (CO) in inhibiting the sequestration of polymorphonuclear neutrophils (PMNs) in the lung following limb ischemia-reperfusion (IR) and the mechanism thereof. METHODS: PMNs of peripheral blood were isolated from the venous blood of a healthy volunteer. Serum was collected from a patient undergoing bilateral knee joint replacement as IR serum. Human pulmonary microvascular endothelial cells (PMVECs) were cultured and divided into 4 groups: control group (cultured under the condition of room air containing 5% CO2 for 5 h and cultured in normal human serum instead of medium during the last 4 hours of experiment), IR group (cultured under the condition of air containing 5% CO2 for 5h and cultured in the serum of IR patient during the last 4 hours), IR + CO group (cultured under the condition of air containing 0.025% CO and 5% CO2 for 5 hours and cultured in IR serum during the last 4 hours), and control + CO group (cultured under the condition of air containing and 0.025% CO and 5% CO2 for 5 hours and cultured in normal human serum during the last 4 hours). Immunofluorescence flow cytometry was used to detect the expression of intercellular adhesion molecule (ICAM)-1 and integrin CD11b in the PMVECs. Human PMVECs were put into the wells of a 96-well plate and added with PMNs to calculate the PMVEC-PMN adhesion rate. Tourniquettes were bound at the bilateral hind thighs of 32 healthy male SD rats for 4 hours so as to establish a rate IR model. The rats were randomly divided into 4 equal groups: control group (undergoing the same operation without causing limb ischemia and exposed to room air), IR group (undergoing bilateral hind limb ischemia for 4 h and reperfusion for 4 h and exposed to room air), IR + CO group (exposed to the containing 0.025% CO one hour before reperfusion till 4 hours after reperfusion), and control + CO group (exposed to air containing 0.025% CO at the corresponding time point as that of the IR + CO group). Then the rats were killed and their middle pulmonary lobes were taken out for microscopy and calculation of the number of PMNs in alveolar septum. Western blotting was used to examine the ICAM-1 protein expression in the lung. RESULTS: The ICAM-1 expression and integrin CD11b expression of the IR group PMVECs were significantly stronger than those of the IR + CO group PMVECs (both P < 0.05) and there were no significant differences in the ICAM-1 expression and CD11b expression between the control + CO and control groups (both P > 0.05). The PMN-PMVEC adhesion rate of the IR group PMVECs was 30 +/- 2.9%, significantly higher than those of the IR + CO group and control group PMVECs (19.8 +/- 1.5% and 13.4 +/- 1.1% respectively, both P < 0.05) and there was no significant difference in the PMN-PMVEC adhesion rate between the CO + control group and control group (P > 0.05). The lung tissues of the IR group rats showed edema and hemorrhage. The number of PMNs in the alveolar septum was 60.6 +/- 1.7/10 high power fields, significantly higher than those of the IR + CO group and control group (36.4 +/- 1.6 and 22.5 +/- 1.6 respectively, both P < 0.05) and there was no significant difference between the latter 2 groups (P > 0.05). The ICAM-1 protein expression in the lung of the IR group was the strongest, followed by the IR + CO group, control + CO group, and control group. CONCLUSION: Exogenous CO inhibits the limb/IR-induced PMN sequestration in the lung, probably by the mechanism of down-regulation of the expression of adhesion molecules and suppression of the PMN\PMVEC adhesion following IR.


Assuntos
Monóxido de Carbono/farmacologia , Neutrófilos/patologia , Traumatismo por Reperfusão/patologia , Síndrome do Desconforto Respiratório/patologia , Animais , Capilares/patologia , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/patologia , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Extremidade Inferior/irrigação sanguínea , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Ativação de Neutrófilo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Síndrome do Desconforto Respiratório/etiologia
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