ObjectiveTo summarize the research status and progress of interleukin-6 (IL-6) in Takayasu arteritis (TAK). MethodRecent literature published at home and abroad about the study of IL-6 in the TAK was reviewed and analyzed. ResultsIL-6 was a pro-inflammatory cytokine secreted by a variety of cells, which participated in a variety of inflammatory and immune reactions, and played an important role in the progress of TAK. The expression levels of IL-6 in the peripheral blood and vascular wall tissues of patients with TAK were increased. The gene polymorphism of IL-6 might be related to the occurrence of TAK. Tocilizumab, an IL-6 receptor antagonist, was effective and safe in the treatment of TAK. ConclusionsIL-6 can be used as one of the monitoring indicators for the active phase and recurrence of TAK. IL-6 receptor antagonist can be used as the treatment choice of TAK, but the application results in different stages of TAK are still worth expecting.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
Objective To investigate the mRNA and protein expression of human β-defensin-2 (hBD-2) induced by lipopolysaccharide (LPS)，IL-1β and TNF-α in human airway primary epitheliums.Methods The bronchial primary epitheliums from human were stimulated with LPS，IL-1β and TNF-α respectively and then were harvested for hBD-2 expression detection.The mRNA expression of hBD-2 was detected by RT-PCR，and the protein expression by immunocytochemistry and western blot.Results There was a small expression of hBD-2 mRNA in human airway primary epitheliums before stimulation.The hBD-2 mRNA expression was significantly increased after 3 hours of LPS，IL-1β and TNF-α stimulation respectively and the expression increasement was in a dose dependent manner.The hBD-2 protein could be detected in cytoplasm after 4 hours of LPS (0.1 μg/mL)，IL-1β (1 ng/mL) and TNF-α (10 ng/mL) stimulation.Conclusions LPS and proinflammatory cytokines can induce the mRNA and protein expression of hBD-2 in a short time.The expression of hBD-2 may play an initial defense role against bacterial invasion.
ObjectiveTo investigate the influence of programmed cell death protein-1 (PD-1) monoclonal antibody on the anti-lung cancer effect of cytokine-induced killer cells (CIK) which were programmed in vitro. MethodsPeripheral blood mononuclear cells from 20 patients (8 males and 12 females with an average age of 56.45±5.89 years ranging from 42 to 65 years) diagnosed with advanced lung cancer from January to May 2019 at the Department of Oncology of Dalian Central Hospital were collected and induced to amplify into CIK cells in vitro. PD-1 monoclonal antibody combined with CIK cell culture group, individual cell culture group and PD-1 monoclonal antibody group were set up to detect the cell killing activity of CIK cells against lung cancer under different effective target ratio conditions, and the ratio of perforin and granzyme positive expression in PD-1 monoclonal antibody combined CIK cell culture group and individual CIK cell culture group was detected by flow cytometry. ELISA method was used to detect the interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) cytokine secretion levels in the two groups.ResultsThe killing effect of CIK cells on A549 lung cancer cells increased with the increase of effective target ratio by CCK8, and PD-1 monoclonal antibody increased the killing effect of CIK cells on A549 lung cancer cells under different effective target ratio, E∶T=5∶1 (28.5%±1.9% vs. 20.3%±1.8%), 10∶1 (40.6%±2.4% vs. 31.7%±2.1%), 20∶1 (57.4%±3.5% vs. 44.7%±3.8%), 40∶1 (74.1%±8.3% vs. 60.8%±5.3%). The killing effect of PD-1 monoclonal antibody combined with CIK cells and CIK cells alone on A549 lung cancer cells was statistically different (P<0.05). The killing effect of cells in both groups on lung cancer A549 cells was stronger than that of the PD-1 monoclonal antibody group (P<0.01). The results of flow cytometry showed that PD-1 monoclonal antibody increased the positive ratio of perforin and granzyme release in CIK cells, and the positive ratios of perforin release (46.7%±3.5%% vs. 35.1%±2.2%) and granzyme release (34.6%±3.8% vs. 25.7%±3.3%) in PD-1 monoclonal antibody combination with CIK cells group and CIK cells group were statistically different (P<0.05). Similarly, the secretion levels of IL-2, TNF-α, and IFN-γ cytokines were also increased in the PD-1 monoclonal antibody combined with CIK cells group compared with the CIK group (5 409.0±168.8 pg/mL vs. 4 300.0±132.3 pg/mL, 252.7±16.7 pg/mL vs. 172.5±8.6 pg/mL, 327.2±23.5 pg/mL vs. 209.7±16.0 pg/mL, P<0.05).ConclusionPD-1 monoclonal antibody can promote the release of tumoricidal substances in CIK cells and improve the killing effect of CIK cells on lung cancer A549 cells. It is speculated that the infusion of PD-1 monoclonal antibody before CIK cell adoption in lung cancer patients may be more beneficial to the treatment of disease. PD-1 monoclonal antibody combined with CIK cell therapy is promising as a new type of lung cancer immunotherapy.
Tree shrew is a novel and high-quality experimental animal model. In this study, the real-time polymerase chain reaction methods were established to detect infection-related cytokines interleukin-6 (IL-6), IL-8, IL-10, IL-17A, interferon-γ (IFN-γ) and housekeeping gene glyceraldehyde-phosphate dehydrogenase (GAPDH) of tree shrew. The results indicated that the establised methods had good specificity. The high point of the linear range of these reagents reached 1 × 1010 copies, and the low points ranged from 10 copies (IL-6, IL-17A), 100 copies (IL-10, GAPDH) to 1 000 copies (IL-8, IFN-γ). In this interval, the linear correlation coefficient R2 of each reagent was greater than 0.99. The lowest detectable values of IL-6, IL-8, IL-10, IL-17A, IFN-γ and GAPDH were 8, 8, 4, 8, 128 and 4 copies, respectively. The results showed that the established detection methods had good specificity, sensitivity and wide linear range. The methods were suitable for detection of multiple concentration range samples, and could be used for the subsequent studies of tree shrew cytokines.
Abstract： Objective To investigate the acute cardioprotective effect of 17b-estradiol (17b-E2) against severe myocardial ischemia/reperfusion (I/R) injury in rabbits and the mechanism of the effect. Methods We established the model of myocardial I/R in vivo by occluding the left anterior descending coronary artery of the rabbits (who underwent coronary occlusion for 40 minutes followed by 3 hours of reperfusion). Twentyfour New Zealand white male rabbits were randomly divided into two groups with 12 in each group. Before coronary occlusion, 1 ml of ethanol or 17b-E2 at 10 μg/kg was administered intravenously to the rabbits in the control group and the experimental group respectively. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzymelinked immunosorbent assay (ELISA) at the following time points: before occlusion, 40 minutes after occlusion, 1 hour, 2 hours and 3 hours after reperfusion. Activation of p38 mitogen activated protein kinase(MAPK) was determined by Western blotting analysis, and apoptosis of cardiocytes was identified by terminal deoxynucleotidlyl transferase mediated deoxyuridinebiotin dUTP Nick End Labeline (TdT)mediated dNTP nick end labeling (TUNEL) staining. Results During myocardial ischemia, TNF-α decreased significantly in the experimental group compared with the control group (F=0.007,P=0.001), while there was no difference in IL-6 between the two groups (F=0.616,P=0.095). During the process of reperfusion, the levels of TNF-α and IL-6 in the experimental group were significantly lower than those in the control group (Plt;0.01). Besides, the activation of p38 MAPK and apoptotic index for the experimental group were also lower (45.07%±2.73% vs. 61.25%±2.41%, t＝－15.398, P=0.000; 11.21%±3.85% vs. 22.02%±4.49%, t＝－6.332, P=0.000). Conclusion The cardioprotective effect of 17b-E2 against myocardial I/R may be attributed to its antiinflammatory and antiapoptotic properties, which is probably associated with the inhibition of 17bE2 on p38MAPK activity.
【摘要】 目的 观察胎羊宫内心脏介入手术胎羊血气及血浆炎性细胞因子的变化。方法 8只怀孕双胎山羊,双胎之一为实验组,在相同麻醉条件下,实验组进行胎羊心脏介入治疗,并抽取血样标本。监测胎羊的心率、血气、乳酸值,运用ELISA法检测治疗组及对照组胎羊白介素(IL)1、IL6、IL8及肿瘤坏死因子(TNFα)。结果 2只胎羊因手术中发生心包填塞死亡,存活的6只胎羊手术前pH值较手术后有明显下降(Plt;005),手术前后乳酸浓度上升(Plt;005),PCO2、PO2差异无统计学意义(Pgt;005),手术前血浆IL1、IL6、IL8的浓度较手术后高(Plt;005),手术前后TNFα的浓度变化无统计学意义(Pgt;005)。结论 胎羊宫内心脏介入手术可引起胎羊血浆pH值下降,乳酸浓度上升,及细胞因子IL1、IL6、IL8浓度上升。【Abstract】 Objective To observe the change of blood gas and inflammatory cytokines during intrauterine cardiac intervention surgery on the fetal lambs. Methods Eight pregnant goats with two fetal in each goat were included. With the same anesthesia condition, one of the twin fetus was chose to perform the intrauterine cardiac intervention surgery. The fetal heart beating rate was monitored, and blood samples of the fetus were taken to do the blood gas analysis and to detect the concentration of inflammatory cytokines (IL1, IL6, IL8, and TNFα). Results Two of the eight fetal lambs which was died in the operation because of pericardial tapenade. In the other six survived fetus, the PH was lower than after the surgery, and the concentrations of lactic acid, IL1, IL6, and IL8 are higher than after the surgery. There was no significant difference of PCO2,PO2 and TNFα between before and after the surgery. Conclusion The intrauterine cardiac intervention surgery can make the PH of fetal plasma lower and the concentrations of lactic acid and IL1, IL6, IL8 higher.
Osteochondral defects is a common clinical joint disease. The complexity of cartilage-bone interface and the poor self-repair capacity of cartilage are both reasons for current relatively limited clinical treatments. The introduction of tissue engineering provides a new treatment method for osteochondral repair. This paper reviews three main elements of cartilage-bone tissue engineering: seed cell source and culture method, cytokines regulation and synergistic effect, and scaffold components and type. We mainly focused on current status quo and future progress of cartilage-bone repair scaffolds. This paper provides some reference for the further development of osteochondral tissue engineering.
Intraocular lymphoma (IOL) is a rare lymphocytic malignancy. The gold standard for the definite diagnosis remains histopathologic examination of the ocular specimen. But cytologic confirmation of malignant lymphoma cells in vitreous or chorioretinal specimens is challenging and dependending on highly skilled cytopathologist, due to the sparse cellularity and specimen degeneration. Consequently, false-negative rates arecommon, which delays diagnosis and treatment seriously. Because of the limited diagnostic capacity of cytology, other adjunct diagnostic tools have been developed. Additional procedures that may support IOL diagnosis include flow cytometry, immunocytochemistry, cytokines study with identification of interleukin (IL)-10 and IL-6 level, and polymerase chain reaction amplification. And more recently, new techniques of mutational analysis have been validated for the diagnosis of vitreoretinal lymphoma (VRL) and may represent a helpful diagnostic tool for the detection of early cases. Metagenomic deep sequencing technology may provide an important basis for VRL diagnosis and personalized treatment. In the future, it is expected to deepen the understanding of IOL disease phenotypes at the molecular level, discover new target therapies, monitor response to treatment, and detect intraocular recurrences. These may offer insights into how we might create a tailored therapeutic approach for each patient's VRL in the future.
Objective To investigate the protective effect of castanospermine (CS) on renal injury induced by severe acute pancreatitis (SAP) in rats and its possible mechanism. Methods Twenty-four SPF adult male Sprague Dawley rats were randomly divided into three groups: shame operation group (SO group, n=8), SAP group (n=8), and CS group (n=8). SAP models were induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) in biliopancreatic duct in the SAP group and the CS group. CS solution (200 mg/kg) was immediately administered via intraperitoneal injection after the induction of pancreatitis in the CS group. Rats in the SO group were subjected to a sham surgery that the pancreas and duodenum were flipped a number of times. All rats were sacrificed at 12 h after modeling. Blood samples were collected by inferior vena cava puncture, and serum activities of amylase (AMY), levels of blood urea nitrogen (BUN) and creatinine (Cr) were measured by using a fully automatic chemistry analyzer. The head of pancreas and renal tissues were harvested and pathological change was observed under the light microscope. Expressions of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and Caspase-3 in renal tissues were evaluated by immunohistochemistry assay. Results ① Compared with the SO group, the damages of the pancreas and kidney tissues were significantly worse in the SAP group, and the above damages in the CS group were significantly decreased when comparing with the SAP group. ② Compared with the SO group, the serum activities of AMY, levels of BUN and Cr were significantly increased in the SAP group (P<0.05). The serum activities of AMY, levels of BUN and Cr in the CS group were significantly lower than those of the SAP group (P<0.05). ③ Compared with the SO group, the integrated optical density (IOD) of NF-κB, TNF-α, ICAM-1, and Caspase-3 in renal tissues were significantly increased in the SAP group (P<0.05), and the above indicators in kidney tissues of the CS group were significantly decreased when comparing with the SAP group (P<0.05). Conclusions CS can mitigate severe acute pancreatitis-induced renal injuries in rats, it ameliorates renal injury and improves renal function. The mechanism for the above improvements is that CS can widely inhibit the activation of NF-κB, and then downregulate the expressions of TNF-α, ICAM-1, and Caspase-3.