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1.
J. coloproctol. (Rio J., Impr.) ; 42(2): 178-186, Apr.-June 2022. graf, ilus
Article in English | LILACS | ID: biblio-1394409

ABSTRACT

ABSTRACT Background and Aims The present systematic review and meta-analysis was designed to estimate the safety and effectiveness of ustekinumab in the treatment of Crohn disease (CD) in clinical trials and observational studies. Methods We retrieved all the related publications from the PubMed, Cochrane, EBSCO, Google Scholar and EMBASE databases using a systematic search strategy. We only included clinical trials and observational studies that were published in English. Results Only 31 studies that met the eligibility criteria out of the 733 identified studies were included. The overall clinical response rate in the cohort studies was of 0.539 (95% confidence interval [95%CI]: 0.419-0.659), and in the clinical trials it was of 0.428 (95%CI: 0.356-0.501). The pooled clinical remission rate was of 0.399 (95%CI: 0.295-0.503) in randomized control trials (RCTs,) and of 0.440 (95%CI: 0.339-0.542) in cohort studies. The rate of adverse effects was of 0.158 (95%CI: 0.109-0.207) in cohort studies and of 0.690 (95%CI: 0.633-0.748) in RCTs. Conclusion Ustekinumab is effective in the treatment of CD. However, more research is required on the safety profiles because there was considerable variation among the included studies. (AU)


Subject(s)
Humans , Crohn Disease/drug therapy , Ustekinumab/therapeutic use , Remission Induction , Treatment Outcome , Ustekinumab/adverse effects , Infections
2.
Rev. méd. Chile ; 150(2): 266-270, feb. 2022. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1389636

ABSTRACT

Sepsis is one of the leading causes of death in critically ill patients with COVID-19 and blood purification therapies have a role to immunomodulate the excessive inflammatory response and improve clinical results. One of the devices designed for these therapies is the oXiris® filter, allowing to perform renal replacement therapy combined with selective adsorption of endotoxins and cytokines. We report a 55-year-old male with COVID who developed a septic shock secondary to a sepsis caused by Pseudomona aeruginosa, refractory to the usual management. A veno-venous continuous hemofiltration was started using the oXiris® filter for 48 hours. Subsequently, there was an improvement in clinical perfusion parameters and a reduction in inflammatory markers. The patient was discharged from the intensive care one month later.


Subject(s)
Humans , Male , Middle Aged , Shock, Septic/complications , Shock, Septic/therapy , Sepsis/complications , COVID-19/complications , Cytokines , Endotoxins
3.
Article in English | WPRIM | ID: wpr-937003

ABSTRACT

@#BACKGROUND: Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis. Our previous study showed that microRNA-761 (miR-761) is overexpressed in hepatocellular carcinoma (HCC) tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis. The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated. METHODS: Exosomal miR-761 was detected in six cell lines. Cell counting kit-8 (CCK-8) and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells. The luciferase reporter assay was used to analyze miR-761 target genes in normal fibroblasts (NFs). The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the transformation of cancer-associated fibroblasts (CAFs). RESULTS: In this study, we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment. We found that HCC-derived exosomal miR-761 was taken up by NFs. Moreover, HCC exosomes affected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2 (SOCS2) and the JAK2/STAT3 signaling pathway. CONCLUSIONS: These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. Our findings may inspire new strategies for HCC prevention and therapy.

4.
Article in Chinese | WPRIM | ID: wpr-936370

ABSTRACT

OBJECTIVE@#To study the cytokine patterns in patients with rheumatoid arthritis (RA) and healthy individuals and identify candidate serum biomarkers for clinical diagnosis of RA.@*METHODS@#This study was conducted among 59 patients diagnosed with RA in our hospital from 2015 to 2019 with 46 age- and gender-matched healthy subjects who received regular physical examinations in our hospital as the control group. Serological autoimmune profiles of 5 RA patients and 5 healthy control subjects were obtained from human cytokine microarrays. We selected 4 differentially expressed cytokines (LIMPII, ROBO3, Periostin and IGFBP-4) and 2 soluble cytokine receptors of interest (2B4 and Tie-2) and examined their serum levels using enzyme-linked immunosorbent assay in 54 RA patients and 41 healthy control subjects. Spearman correlation test was performed to assess the correlation of serum cytokine and soluble receptor expression levels with the clinical features including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28) and health assessment questionnaire (HAQ). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these cytokines.@*RESULTS@#We identified 6 dysregulated cytokines and soluble receptors (2B4, LIMPII, Tie-2, ROBO3, periostin and IGFBP-4) in RA patients (P < 0.01). The serum levels of LIMPII, ROBO3 and periostin were significantly correlated with the disease activity indicators including RF (P < 0.001), CRP (P < 0.001), DAS28 (P < 0.001) and HAQ (P < 0.001) in RA patients. Among the 6 candidate cytokines, 2B4 showed the largest area under the curve (AUC) of 0.861 for RA diagnosis (P < 0.001), followed then by LIMPII, ROBO3, periostin, Tie-2 and IGFBP-4.@*CONCLUSION@#Serum levels of LIMPII, ROBO3 and periostin can be indicative of the disease activity of RA, and serum 2B4, LIMPII, periostin, ROBO3, IGFBP-4 and Tie-2 levels may serve as biomarkers for the diagnosis of RA.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Biomarkers , C-Reactive Protein , Cytokines , Humans , Insulin-Like Growth Factor Binding Protein 4 , Protein Array Analysis , Receptors, Cell Surface
5.
Acta Pharmaceutica Sinica B ; (6): 876-889, 2022.
Article in English | WPRIM | ID: wpr-929332

ABSTRACT

SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

6.
Journal of Integrative Medicine ; (12): 274-280, 2022.
Article in English | WPRIM | ID: wpr-929222

ABSTRACT

OBJECTIVE@#Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.@*METHODS@#A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.@*RESULTS@#The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.@*CONCLUSION@#This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.


Subject(s)
Abietanes , Acute Lung Injury/drug therapy , Animals , Cytokine Release Syndrome , Cytokines , Inflammation/drug therapy , Lipopolysaccharides/toxicity , Macrophage Activation , Macrophages , Mice , Triacetoneamine-N-Oxyl/pharmacology
7.
Frontiers of Medicine ; (4): 285-294, 2022.
Article in English | WPRIM | ID: wpr-929193

ABSTRACT

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade ⩾ 3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.


Subject(s)
Antigens, CD19/adverse effects , China , Humans , Lymphoma, Large B-Cell, Diffuse/therapy , Receptors, Chimeric Antigen , T-Lymphocytes
8.
Clin. biomed. res ; 42(2): 128-134, 2022.
Article in English | LILACS | ID: biblio-1391544

ABSTRACT

Introduction: Considering the lack of specific treatments for neuropathic pain, this study aimed to evaluate the effect of a single dose of adenosine A3 receptor IB-MECA on inflammatory and neurotrophic parameters in rats subjected to a neuropathic pain model. Methods: 64 adult male Wistar rats were used. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve and the treatment consisted of a 0.5 µmol/kg dose of IB-MECA, a selective A3 adenosine receptor agonist, dissolved in 3% DMSO; vehicle groups received DMSO 3% in saline solution, and morphine groups received 5 mg/kg. Cerebral cortex and hippocampus IL-1ß, BDNF, and NGF levels were determined by Enzyme-Linked Immunosorbent assay. Results: The main outcome was that a single dose of IB-MECA was able to modulate the IL-1ß hippocampal levels in neuropathic pain induced by CCI and the DMSO increased IL-1ß and NGF hippocampal levels in sham-operated rats. However, we did not observe this effect when the DMSO was used as vehicle for IB-MECA, indicating that IB-MECA was able to prevent the effect of DMSO. Conclusions: Considering that the IL-1ß role in neuropathic pain and the contributions of the hippocampus are well explored, our result corroborates the relationship between the A3 receptor and the process of chronic pain maintenance.


Subject(s)
Animals , Male , Rats , Neuralgia/diagnosis , Neuralgia/metabolism , Nerve Growth Factor/genetics , Nerve Growth Factor/metabolism , Receptor, Adenosine A3/therapeutic use
9.
Article in Chinese | WPRIM | ID: wpr-934047

ABSTRACT

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

10.
Article in Chinese | WPRIM | ID: wpr-934029

ABSTRACT

SARS-CoV-2, the pathogen of the COVID-19 pandemic, causes serious damage to human health and social stability. In severe COVID-19 cases, the infection triggers cytokine storm, resulting in multi-organ excessive inflammatory responses and even failure, which eventually leads to death. Recent studies have shown the activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays an essential role in the pathogenesis of COVID-19. SARS-CoV-2 can activate NLRP3 inflammasome through several pathways, thereby inducing the release of a large number of pro-inflammatory cytokines. This article reviews the activation of NLRP3 inflammasome caused by SARS-CoV-2 infection and the possible molecular mechanisms, and summarizes the progress in targeted inhibition of NLRP3 inflammation, aiming to provide a new strategy for the treatment of SARS-CoV-2 infection.

11.
Article in Chinese | WPRIM | ID: wpr-934015

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic and recurrent disease characterized by chronic inflammation of the gastrointestinal tract. The quality of life of patients with IBD is seriously affected. The pathogenesis of IBD is complex, among which immune factors are considered to be the predominant factor. Leptin is a hormone derived from adipocytes and recent studies have shown that it is involved in the regulation of immune cells and inflammatory signaling pathways. This review summarized the pathogenesis of IBD, the immunoregulatory mechanism of leptin and research progress in immune modulators, introduced the potential effects of leptin on the regulation of immunological homeostasis in IBD and its potential roles in the etiology and pathogenesis of IBD, and discussed a possible immunotherapy method to treat IBD through leptin antagonist to reduce the inflammatory response and inhibit the inflammatory signaling pathways.

12.
Article in Chinese | WPRIM | ID: wpr-934014

ABSTRACT

Objective:To detect the inflammatory reaction of macrophages induced by lipoglycans of different genotypes of Mycobacterium tuberculosis ( Mtb) in vitro and to analyze the differences in lipoglycan virulence. Methods:Lipoglycans were extracted from Mtb of Beijing, T1 and MANU2 genotypes and H37Rv by Triton X-114 liquid phase method and the crude extracts of lipoglycans was used to stimulate RAW264.7 macrophages. Changes in cytokine and receptor expression and cell apoptosis were detected 24 h after stimulation. The virulence of lipoglycans from different genotypes of Mtb was analyzed and compared. One-way analysis of variance and Tukey′s multiple comparisons test were used to compare the differences in various indexes between groups. Results:The expression of IL-10 at mRNA level induced by lipoglycans from Mtb of Beijing, T1 and MANU2 genotypes and H37Rv was (0.94±0.24), (1.86±0.24), (1.90±0.24) and (2.55±0.75) times that of the control group. Moreover, IL-10 mRNA expression induced by lipoglycans from Mtb of Beijing genotype was significantly lower than that of H37Rv group ( P<0.05). After stimulating RAW264.7 cells with the crude extracts of lipoglycans, the proportions of living cells in H37Rv, Beijing genotype, T1 genotype and MANU2 genotype groups were (72.75±2.25)%, (60.99±0.13)%, (80.66±0.40)% and (79.06±1.19)%, and the total cell apoptosis ratios was (10.42±0.23)%, (8.30±0.03)%, (9.24±0.79)% and (8.04±0.48)%, respectively. The proportion of living cells in Beijing genotype group was the lowest ( P<0.05), and the proportions of living cells in T1 and MANU2 genotype groups were higher than that in H37Rv group ( P<0.05). There was no significant difference in cell apoptosis ratio among the groups ( P>0.05). Lipoglycan-induced cell death was increased in Beijing genotype group, and the lipoglycan from Beijing genotype Mtb was more virulent than those from Mtb of T1 and MANU2 genotypes. Conclusions:Lipoglycan from Mtb of Beijing genotype could induce a higher level of cell death in vitro. It was an antigen component with stronger virulence than those from Mtb of T1 and MANU2 genotypes.

13.
Article in Chinese | WPRIM | ID: wpr-934011

ABSTRACT

Objective:To investigate the effects of IL-28B in a mouse model of dextran sulfate sodium (DSS)-induced colitis and to analyze the possible mechanism.Methods:Thirty-five male C57BL/6 mice were randomly divided into the following groups with seven mice in each group: control group, DSS group and three IL-28B groups (1.25 μg, 2.5 μg and 5 μg). The mice in the DSS group and IL-28B groups were fed with 2.5% DSS solution and from day 3, the IL-28B groups were given intraperitoneal injection of corresponding IL-28B every day and the DSS group was treated with PBS. During the experiment, the disease activity index (DAI) was evaluated daily. On day 8, the mice were sacrificed and peripheral blood, spleen, mesenteric lymph node and colon samples were collected. The colon samples were observed, measured in length and stained with HE, and histopathological scores were calculated based on HE staining. Changes of immune cells in different samples were detected by flow cytometry. ELISA was used to detect the expression of IL-12, IL-10, IL-1β, IL-6, IL-4 and IL-13 in serum and colon tissues.Results:Compared with the DSS group, the IL-28B group (2.5 μg) had lower DAI scores [(9.40±1.67) vs (3.50±1.73), P<0.01], less shortening of the colon [(5.16±0.61) cm vs (6.91±0.60) cm, P<0.01] and significantly lower histopathological scores [(7.33±0.58) vs (4.33±0.58), P<0.01]. Moreover, compared with the DSS group, the IL-28B group (2.5 μg) showed decreased macrophages in the peripheral blood [(21.39±3.21)% vs (15.63±2.98)%, P<0.05] and spleen [(3.03±0.28)% vs (2.05±0.48)%, P<0.05], and significantly increased mean fluorescence intensity of M2 macrophages in the colon [(1 361.00±293.40) vs (2 074.00±87.61), P<0.05]. IL-12 expression in colon tissues and IL-1β expression in serum were reduced, and IL-10, IL-4 and IL-13 expression in colon tissues was significantly increased in the IL-28B group (2.5 μg) as compared with those in the DSS group [IL-12: (31.72±6.92) pg/mg vs (5.41±3.41) pg/mg; IL-1β: (48.01±16.13) pg/ml vs (12.27±6.26) pg/ml; IL-10: (184.70±46.82) pg/mg vs (444.30±157.80) pg/mg; IL-4: (2.23±0.27) pg/mg vs (3.64±0.80) pg/mg; IL-13: (11.79±0.99) pg/mg vs (22.59±1.92) pg/mg; all P<0.05]. Conclusions:IL-28B might alleviate the severity of acute enteritis in mice by increasing the secretion of IL-4 and IL-13, regulating macrophage differentiation and modulating the expression of inflammatory factors.

14.
Article in Chinese | WPRIM | ID: wpr-934010

ABSTRACT

Objective:To establish a method using activation-induced markers (AIM) to detect the function of HIV-1-specific CD4 + T cell subsets for evaluating the immune response of HIV-1-specific CD4 + T cells more effectively. Methods:Twelve chronically HIV-1-infected patients without antiviral therapy and six healthy people without HIV-1 infection were enrolled in this study. The function of HIV-1-specific T lymphocytes was detected by AIM and ICS based on polychromatic flow cytometry. The performance of the two methods in assessing HIV-1-specific CD4 + T cell immune response in HIV-1-infected patients was evaluated. Results:The positive rates of HIV-1-specific PD-1 + CD25 + CD4 + T, CD69 + CD200 + CD4 + T, CD69 + ICOS + CD4 + T, CD69 + ICOS + CD8 + T、CD137 + CD69 + CD8 + T、PD-1 + CD25 + CD8 + T and OX40 + PD-1 + CD8 + T cells in all of the HIV-1 patients were 11/12, 8/12, 7/12, 8/12, 8/12, 7/12 and 7/12 using AIM method. ICS results showed that the positive rates of HIV-1-specific IL-2 + CD4 + T, IFN-γ + CD4 + T, TNF-α + CD4 + T, IFN-γ + CD8 + T, TNF-α + CD8 + T and IL-2 + CD8 + T cells were 2/12, 2/12, 0, 12/12, 10/12 and 5/12, respectively. Conclusions:AIM method was more sensitive in antigen-specific CD4 + T cell detection, and could be used as a complementary method to ICS in assessing antigen-specific T cell response.

15.
Article in Chinese | WPRIM | ID: wpr-931229

ABSTRACT

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has caused a devastating health crisis worldwide.In this review,we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic.The following evidence supports our argu-ment.First,nuclear factor erythroid-derived 2-like 2(NRF2)agonists abrogate replication of SARS-CoV-2 in lung cells,and quercetin is a potent NRF2 agonist.Second,quercetin exerts antiviral activity against several zoonotic coronaviruses,including SARS-CoV-2,mainly by inhibiting the entry of virions into host cells.Third,inflammatory pathways activated by nuclear factor kappa B,inflammasome,and interleukin-6 signals elicit cytokine release syndrome that promotes acute respiratory distress syndrome in patients with COVID-19,and quercetin inhibits these pro-inflammatory signals.Fourth,patients with COVID-19 develop thrombosis,and quercetin mitigates coagulation abnormalities by inhibiting plasma protein disulfide isomerase.This review provides a strong rationale for testing quercetin for the management of COVID-19.

16.
Article in Chinese | WPRIM | ID: wpr-930861

ABSTRACT

Objective:To study the changes of cytokines after cardiopulmonary bypass(CPB)in children with congenital heart disease.Methods:A total of 124 children with congenital heart disease underwent CPB surgery at Shanghai Children′s Medical Center from June 2020 to October 2021 with cytokine detection were enrolled.Twelve kinds of cytokines, white blood cell count(WBC)and neutrophil-to-lymphocyte ratio(NLR), C-reactive protein(CRP)and procalcitonin were detected before and 24 hours after operation.All patients were divided into CPB<120 min group ( n=102)and CPB≥120 min group ( n=22)acoording to CPB time, and were divided into systemic inflammatory response syndrome (SIRS) group, compensatory anti-inflammatory response syndrome (CARS) group and control group according to the changes of cytokines.The changes of cytokines, anti-inflammatory factors and pro-inflammatory factors before and after CPB and the correlation with CPB time were analyzed. Results:There were 65 boys and 59 girls with a body weight of(10.69±8.18)kg and a median age of 317(141, 975)d.After CPB, WBC(×10 9/L)(13.47 vs.8.6), NLR(4.93 vs.0.55), and CRP(mg/L)(81.35 vs.0.8) were significantly higher than those before operation( P<0.001). IL-6(pg/mL)(135.69 vs.6.86), IL-8(pg/mL)(33.33 vs.14.95), and IL-10(pg/mL)(6.05 vs.2.44)were significantly higher than those before operation( P<0.001). Compared with CPB<120 min group, IL-6(pg/mL)(211.88 vs.119.47), IL-8(pg/mL)(71.67 vs. 25.39), and IL-10(pg/mL)(7.69 vs. 4.92)in CPB≥120 min group significantly increased( P<0.001). CRP was negatively correlated with CPB time( r=-0.204, P=0.025), while IL-6( r=0.254, P=0.005), IL-8( r=0.358, P=0.001), IL-10( r=0.198, P=0.03) were positively correlated with CPB time.Twelve children(9.7%)had obvious SIRS, and four cases(3.2%)had early CARS.The mortality of CARS group was significantly higher than that of SIRS group and the control group( P=0.011). Conclusion:Il-6 , IL-8, and IL-10 are significantly increased after CPB in children with congenital heart disease.With the increase of CPB time, IL-6 and IL-8 increase significantly, and the correlation between IL-8 and CPB time is the strongest.Although the proportion of children with early postoperative CARS is small, the mortality is high, which indicates clinical surveillance and treatment need to be strengthened for anti-inflammatory response.

17.
Article in Chinese | WPRIM | ID: wpr-930837

ABSTRACT

Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.

18.
Article in Chinese | WPRIM | ID: wpr-930484

ABSTRACT

Objective:To summarize the clinical features of children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae.Methods:A total of 36 children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae (coinfection group) diagnosed in the Wuhan Children′s Hospital from December 1, 2018 to September 1, 2019 were enrolled.Their clinical manifestations, laboratory examinations, and imaging findings were retrospectively analyzed.In the same period, 94 children with single human adenovirus type 7 infection pneumonia were selected as the single infection group.Differences between 2 groups were compared using the Student′s t-test, rank sum test and Chi- square test. Results:In the coinfection group, 25 cases were males, 11 cases were females, their mean age was 3.11 years.The main clinical manifestations included fever (97.2%) and cough (100.0%). The mean body temperature was 40.0 ℃, with the thermal peak of 4 times per day, and the mean course of fever of 11 days.The incidence of severe pneumonia was significantly higher in coinfection group (86.1%) than that of single infection group (69.1%) ( χ2=3.878, P<0.05). The common complications included myocardial damage (55.5%), heart failure (16.7%), liver function damage (25.0%), gastrointestinal bleeding (5.5%), toxic encephalopathy (11.0%), hemophagocytic syndrome (16.7%), and bronchiolitis obliterans (50.0%). The levels of cytokines like interleukin (IL)-6 [237.84(108.59, 606.36) ng/L], IL-10[31.44(12.13, 69.60) ng/L]and interferon-γ [(102.85±92.23) ng/L] were obviously elevated, and among them, IL-6 and IL-10 elevations were significantly pronounced in coinfection group than that of single infection group[148.35(57.43, 390.82); 19.67(10.96, 35.35)] ( Z=-1.984, -2.077, all P<0.05). Lung consolidation (50.0%) and pleural effusion (38.9%) were common in coinfection group, and the incidence of pleural effusion in coinfection group was significantly higher than that of single infection group (19.1%)( χ2=5.594, P<0.05). Conclusions:Most of the pneumonia caused by human adenovirus type 7 mixed Mycoplasma pneumoniae in children is severe pneumonia, which may be related to the cytokine storm.

19.
Article in Chinese | WPRIM | ID: wpr-930214

ABSTRACT

Objective:To explore the characteristics of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis (HLAP) and its prognostic value.Methods:This study included 184 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2021. Based on disease etiology, there were 92 HLAP cases and 92 non-hyperlipidemia-induced AP (NHLAP) cases. Stratified by disease severity according to 2012 Atlanta classification criteria, the patients were divided into the severe subgroup (SAP) and non-severe subgroup (NSAP). Peripheral venous blood samples were taken from all patients on day 1, 3, and 5 after admission. T lymphocyte subsets were determined by flow cytometry, and cytokines were detected by flow fluorometry. The number of CD4 +% and CD8 +% and the expression of cytokines were compared by Student’s t test or Mann-Whitney U analysis. Logistic regression analyses were performed to identify risk factors for severe AP, and a receiver operating characteristic (ROC) curve was constructed to predict severe AP. Statistical significance was taken as P<0.05. Results:Compared with the NHLAP group, patients in the HLAP group had lower CD4 +%, while higher levels of IL-2 on day 1 ( P<0.05), and had also lower CD4 +%, while higher levels of IL-4, IL-6, and IL-10 on day 3 ( P<0.05). Furthermore, IL-6 and IL-10 levels of the HLAP group were significantly increased compared to the NHLAP group on day 5 ( P<0.05). IL-10 levels in the SAP subgroup were significantly higher than those in the NSAP subgroup on day 1 ( P<0.05). Compared with the NSAP subgroup, the SAP subgroup had elevated levels of IL-2, IL-4, IL-6, IL-10 and IFN-γ on day 3 (all P<0.05), and had lower CD4 +%, while increased levels of IL-6 and IL-10 on day 5 (all P<0.05). Multivariate Logistic regression analysis showed that IL-10 was an immune indicator of independent risk factor for severe AP in the HLAP group on day 1 ( OR=1.139, 95% CI: 1.038-1.251, P<0.05). Finally, ROC analysis showed that the area under the curve of IL-10 to assess HLAP with severe AP was 0.772, and the best cut-off value for predicting severe AP was 5.6 pg/mL, with a sensitivity of 83.3% and a specificity of 68.8%. Conclusions:Changes of CD4 +% and cytokines are different between the HLAP and NHLAP groups. IL-10 can be used as a predictor of early disease severity in patients with HLAP.

20.
Article in Chinese | WPRIM | ID: wpr-930153

ABSTRACT

Objective:To explore the efficacy of Fuzheng Zhuyu Xiehuo Decoction for the patients with acute pancreatitis (AP) of intermingled blood stasis-toxin syndrome and its influence on peripheral blood inflammatory factors and microcirculation indicators.Methods:A total of 100 patients with AP, admitted to department of spleen and stomach diseases of the First Affiliated Hospital of Hunan University of Chinese Medicine and department of gastroenterology of the Central Hospital of Shaoyang, who met the inclusion criteria between March 2019 and March 2020, were divided into two groups according to the random number table method, with 50 in each group. The control group was given conventional western medicine, while the observation group was treated with Fuzheng Zhuyu Xiehuo Decoction on the basis of the control group. The TCM syndromes were scored before and after treatment, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) was used to evaluate the severity of the disease, and ELISA was adopted to detect the levels of IL-6, IL-8, TNF-α and thromboxane A2 (TXA2), prostaglandin I 2 (PGI 2) and platelet activating factor (PAF). The abdominal pain, abdominal distension, fever, gastrointestinal function recovery time and hospital stay were observed and the adverse events were recorded. Results:The total effective rate was 96.0% (48/50) in the observation group and that of the control group was 84.0% (42/50) ( χ2=4.00, P=0.045). The scores of abdominal pain, abdominal distension, fever and nausea and vomiting in observation group were significantly lower than those in the control group ( t=7.07, 7.06, 11.47, 10.30, all Ps<0.01), and the recovery times of abdominal pain, abdominal distension, fever and gastrointestinal function and hospital stay in the observation group were significantly shorter than those in the control group ( t=4.52, 4.90, 6.27, 6.55, 7.12, all Ps<0.01). After treatment, the levels of serum IL-6 [(30.15±7.04) μg/L vs. (42.37±8.29) μg/L, t=7.95], IL-8 [(39.36±8.11) μg/L vs. (50.36±10.47) μg/L, t=5.87], TNF-α [(106.28±21.04) μg/L vs. (153.45±30.23) μg/L, t=9.06] in the observation group were significantly lower than those in the control group ( P<0.01). The serum TXA2 [(223.68±40.15) ng/L vs. (257.11±50.32) ng/L, t=3.67] and PAF [(74.86±15.37) ng/L vs. (85.53±15.26) ng/L, t=3.48] in the observation group were significantly lower than those in the control group ( P<0.01) while the level of PGI 2 [(91.43±17.45) ng/L vs. (76.49±15.13) ng/L, t=4.57] in the observation group was significantly higher than those in the control group ( P<0.01). Conclusion:Fuzheng Zhuyu Xiehuo Decoction combined with western medicine can improve clinical symptoms and blood microcirculation status, relieve inflammatory response and enhance clinical efficacy of patients with AP of intermingled blood stasis-toxin syndrome.

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