Objective To explore the clinical effect of hemoperfusion (HP) in cardiopulmonary bypass (CPB) on postoperative inflammation in patients with acute type A aortic dissection (AAD). MethodsAdult patients with AAD who planned to undergo total aortic arch replacement from July 2020 to November 2021 were continuously enrolled in our heart center. Patients were randomly divided into a HP group and a control (C) group. The HP group was treated with disposable HP device (Model: HA380, Zhuhai Jafron Biomedical, China) in CPB during the operation. ResultsFinally, 70 patients were included with 59 males and 11 females at an age range of 21-67 years. There were 35 patients in both groups. In this study, 3 patients died within 3 days after surgery, 2 in the HP group and 1 in the C group, and the remaining 67 patients survived to the follow-up end point (30 days after surgery). There was no statistical difference in preoperative baseline data, operative method, CPB time, block time, or other intraoperative data between the two groups. Blood product dosage, intubation time, hospital stays, and hospitalization expenses were similar between the two groups. Intraoperative hemoglobin (82.70±2.31 g/L vs. 82.50±1.75 g/L, P=0.954] and platelet concentration [(77.87±7.99)×109/L vs. (89.17±9.99)×109/L, P=0.384] were not statistically different between the HP group and C group. In the HP group, postoperative (ICU-12 h) interleukin-6 (IL-6) [338.14 (128.00, 450.70) pg/mL vs. 435.75 (180.50, 537.00) pg/mL, P=0.373], IL-8 [35.04 (18.02, 40.35) pg/mL vs. 43.50 (17.70, 59.95) pg/mL, P=0.383], and IL-10 [21.19 (6.46, 23.50) pg/mL vs. 43.41 (6.34, 50.80) pg/mL, P=0.537] were slightly lower than those in the C group, and the difference was not statistically different. The incidences of pulmonary infection (0.00% vs. 11.76%, P=0.042) and liver injury (2.94% vs. 20.58%, P=0.027) in the HP group were significantly lower than those in the C group, and the incidence of other postoperative complications, such as arrhythmia, nervous system complications and urinary system complications, showed no statistical difference between the two groups. Conclusion HP therapy in CPB is safe, but its effect on reducing postoperative inflammatory factors, postoperative inflammatory reactions and postoperative complications in the patients with AAD is limited, and it may be of application value to some high-risk patients with lung and liver injury.
Objective To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union. Methods The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union. Results Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity. Conclusion TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.
ObjectiveTo investigate the expression of α7 nicotinic acetylcholine receptor (α7 nAChR) in thymocytes of patients with myasthenia gravis (MG) and its effect on cytokine secretion and T cell proliferation. MethodsPatients with MG who underwent expanded thoracoscopic thymectomy in the Comprehensive Diagnosis and Treatment Center of the Henan Provincial People’s Hospital from June 2021 to June 2022 were selected and allocated to a MG group. Patients who underwent partial thymectomy to expose the surgical field during the cardiac disease surgery from June 2021 to September 2022 in the Department of Adult Cardiac Surgery of Fuwai Huazhong Cardiovascular Hospital were selected as the control group. Thymic single cell suspensions were prepared from MG and control groups, and the expression of α7 nAChR in thymocytes of the two groups was detected by real-time polymerase chain reaction and Western blotting. Then CD3/CD28 monoclonal antibody coupled with magnetic beads was used to induce T cell activation, and the levels of cytokines interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, IL-17, and IL-21 in thymocytes of the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The activated T cells of the MG group were divided into a blank control group, an α7 nAChR antagonist group, and an α7 nAChR agonist group according to different treatment methods. After 72 hours of culture, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, and IL-21 expression levels in the culture supernatant were measured by ELISA. Afterwards, CD4-PE and CD8-APC antibodies were added, and the proliferation of T cell subsets was detected by flow cytometry. ResultsA total of 10 MG patients were collected, including 3 males and 7 females with an average age of 19.25±6.28 years; and 15 control patients were collected, including 6 males and 9 females with an average age of 26.18±6.77 years. Compared with the control group, the mRNA and protein levels of α7 nAChR in the thymocytes of MG group were decreased, and the expression levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-21 in the supernatant were increased (P<0.05), but there was no statistical difference in the expression of IL-10 and IL-17 (P>0.05). The cell-culture experiment showed that compared with the blank control group, the levels of IFN-γ, TNF-α, IL-6 and IL-21 secreted by T cells in the α7 nAChR antagonist group were increased (P<0.05), while they were decreased in the α7 nAChR agonist group (P<0.05). There was no statistical difference in the secretion levels of IL-4, IL-10 or IL-17 among the three groups (P>0.05). CD4+ T and CD8+ T cells in the α7 nAChR agonist group were significantly less than those in the blank control group and α7 nAChR antagonist group (P<0.001), while they were significantly more in the α7 nAChR antagonist group than those in the blank control group (P<0.001).ConclusionThe expression of α7 nAChR in thymocytes of MG patients is decreased, and α7 nAChR may be involved in the inflammatory response in thymocytes and thus in thymic function.
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.
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.
Myocardial remodeling is a common pathological physiology change for a variety of heart diseases under stimulation such as stress or ischemia. The engine body will release a lot of cytokines to promote the change of myocardial structure and ultimately lead to heart failure. Myocardial remodeling includes myocardial cells remodeling and the extracellular matrix remodeling. In recent years, we find that the function of adipose tissue is not only about energy storage, buffering to protect, supporting and filling, but also has a powerful function of secretion. Adipose tissue can secrete various adipocytokines, such as leptin, adiponectin, visfatin, omentin, angiotensin Ⅱ, and so on. Current studies have shown that adipocytokines and myocardial remodeling are intimated. And this article will summarize the function of adipocytokines on myocardial remodeling.
Objective To investgate the expression of p38 mitogen-activated protein kinase （p38MAPK） in lung tissue of rats with severe acute pancreatitis （SAP）， and to explore the relationship between p38MAPK and pulmonary capillary barrier injury. Methods Forty male and healthy Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation （SO） group and SAP group， then rats of SAP group were sub-divided into 3， 6， 12， and 24 h group， each group enrolled 8 rats， respectively. SAP model rats were established by injecting 5% sodium taurocholate solution retrograde into the biliopancreatic duct. ELISA method was used to test the serum tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and pathological changes in lung and pancreas tissues were observed by HE staining. Immunohischemistry method was used to detect phosphorylated p38 （p-p38） protein and aquaporin 1 （AQP1） protein of lung tissues. The expression level of AQP1 mRNA was measured by quantitative real-time PCR. Results Hyperemia， edema， and inflammatory cell infiltration were observed in lung tissues， abundance of necrosis， part gland structure fuzzy or even disappear were observed in pancreas tissues of all 4 time point groups. Compared with SO group， levels of serum TNF-α and IL-1β were significantly higher in 4 time point groups （P＜0.05）. Lower expression level of p-p38 protein was detected in lung tissues of SO group， while in the early stage of SAP （SAP 3 h group）， the expression level of p-p38 protein significantly increased， which peaked in 6 h group and was still higher than SO group in 24 h group （P＜0.05）. Compared with SO group， the expression levels of AQP1 mRNA and protein were significantly lower in all 4 time point groups （P＜0.05）， which had negative correlation with the levels of serum TNF-α，IL-1β， and the expression level of p-p38 protein （r=-0.87， P＜0.05；r=-0.88， P＜0.05；r=-0.78， P＜0.05）. Conclusion The decrease of AQP1 protein in lung tissue is one of the vital causes for pulmonary capillary barrier injury in SAP， which probably works by the activation of p38MAPK and the excessive release of inflammatory cytokines.
Objective To review the application and research progress of in-situ tissue engineering technology in bone and cartilage repair. Methods The original articles about in-situ tissue engineering technology in bone and cartilage repair were extensively reviewed and analyzed. Results In-situ tissue engineering have been shown to be effective in repairing bone defects and cartilage defects, but biological mechanisms are inadequate. At present, most of researches are mainly focused on animal experiments, and the effect of clinical repair need to be further studied. Conclusion In-situ tissue engineering technology has wide application prospects in bone and cartilage tissue engineering. However, further study on the mechanism of related cytokines need to be conducted.
Objective To investigate the effects of glutathione S-transferase M5 (GSTM5) on the inflammation in human bronchial epithelial 16HBE cells and its possible molecular mechanisms. Methods Acute lung injury cell model was constructed with 16HBE cells induced by tumour necrosis factorα (TNF-α, 10 ng/mL). The cells were devided into a control group, a TNF-α group (TNF-α), a GSTM5 group (GSTM5+TNF-α), a negative control group (negative control plasmid+TNF-α). GSTM5-GFP plasmid and negative control plasmid were respectively transfected to the cells of the GSTM5 group and the negative control group using Lipofectamine2000. The contents of interleukin-6(IL-6), IL-8, IL-10 in the cell supernatant were measured by ELISA.The expression of nuclear factor-κB (NF-κB) mRNA was detected by RT-PCR, and the expression of NF-κB, phospho-NF-κB, p38, phospho-p38 protein were detected by Western blot. Results The GSTM5-GFP eukaryotic expression vector was successfully constructed and transfected successfully confirmed by fluorescence microscope. The contents of IL-6, IL-8, IL-10 in the TNF-α-induced cell supernatant were significantly higher than those in the control group(P < 0.05), and the contents of IL-6, IL-8, IL-10 in the GSTM5 group were lower than those in the TNF-α group (P < 0.05)with statistically significant difference. At the same time, the total NF-κB mRNA, phospho -NF-κB and phospho-p38 protein were increased in TNF-α stimulated cells compared with the control group (P < 0.05), while the GSTM5 group was lower than that in the TNF-α group and the negative control group (P < 0.05). Conclusion Overexpression of GSTM5 inhibits the phosphorylation of p38MAPK and NF-κB and down-regulates the inflammation of TNF-α-induced human bronchial epithelial 16HBE cells.
Objective To identify the effects of single immunoglobin IL-1 receptor related protein （SIGIRR） on inflammation induced by high mobility group box 1 （HMGB1） in A549 derived from human alveolar epithelial cells. Methods Eukaryotic expression vectors pCDNA3.1（+） constructed with SIGIRR cDNA were transiently transfected into A549 cells，in which SIGIRR was forced to be over-expressed. Western blot and RT-PCR were applied to detect the expression level of SIGIRR after transfection. After the stimulation by HMGB1，the transcriptional activity of NF-κB in A549 cells was detected by dual-luciferase reporter assay system，and the protein levels of inflammatory cytokine TNF-α and IL-1β were measured by ELISA. Results The expression level of SIGIRR increased significantly in A549 cells transfected with SIGIRR vectors. The transcriptional activity of NF-κB was enhanced obviously after HMGB1 treatment in A549 cells by dual-luciferase reporter assay system，while the transfection of SIGIRR vectors decreased the activity. The protein levels of TNF-α and IL-1β were down-regulated in A549 cells over-expressing SIGIRR after HMGB1 stimulation compared with the non-transfected cells. Conclusions Up-regulated SIGIRR expression can inhibit HMGB1-induced proinlammatory cytokine release in A549 cells such as TNF-α and IL-1β. The transcriptional activity of NF-κB is dampened by SIGIRR transfection，implying that the anti-inflammatory effects of SIGIRR may be involved in the regulation of NF-κB.