ObjectiveTo investigate the safety and clinical efficacy of dendritic cell (DC)-cytokine induced killer (CIK) cell adoptive immunotherapy combined with chemotherapy in patients with gastric cancer after radical gastrectomy.MethodsForty-eight patients with gastric cancer after the radical gastrectomy receiving the DC-CIK cell adoptive immunotherapy combined with XELOX or FOLFOX chemotherapy were enrolled as a study group in the First Hospital of Lanzhou University from January 2014 to January 2016. In addition, 48 patients with gastric cancer after the radical gastrectomy in the same period and only receiving XELOX or FOLFOX chemotherapy were collected as a control group. The CD3+, CD3+CD4+, CD3+CD8+, CD3–CD56+ (NK cell), and CD3+CD56+ (NKT cell), toxic reaction, quality of life were evaluated in both groups before and after the treatment, and the long term effect were compared in both groups.Results① There were no significant differences in the gender, age, clinical stage, etc. between the two groups (P>0.05). ② The CD3+, CD3+CD4+, CD3+CD8+, CD3–CD56+, and CD3+CD56+ cells in the peripheral blood had no significant changes between before and after treatment in the study group (P>0.05), which were decreased after the treatment in the control group as compared with before the treatment and were significantly lower than those in the study group (P<0.05). ③ The levels of CEA, CA19-9, and CA724 in the peripheral blood after the treatment in the study group and the control group were significantly lower than those before the treatment (P<0.05), which in the study group were significantly lower than those in the control group after the treatment (P<0.05). ④ The incidences of leukopenia, thrombocytopenia, and diarrhea in the study group were significantly lower than those in the control group (P<0.05). ⑤ Compared with before the treatment, the body function and emotional function after the treatment were significantly improved in the study group (P<0.05). And in the body function, emotion function, role function, cognitive function, and social function were significantly improved than those in the control group (P<0.05) after the treatment. ⑥ The progression-free survival in the study group was significantly better than that in the control group (P<0.05). There was no significant difference in the overall survival between the study group and the control group (P>0.05).ConclusionDC-CIK cell adoptive immunotherapy combined with chemotherapy could significantly improve immune status and quality of life of patients with gastric cancer after radical gastrectomy, reduce adverse effects of chemotherapy, improve long term effect, and prolong progression-free survival.
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.
Myasthenia gravis (MG) is a common antibody mediated, cell-mediated, and complement dependent neuromuscular junction immune disease. The treatment mainly includes drug therapy (symptomatic therapy, non-specific immunosuppressive therapy, targeted immunotherapy), immune regulation (intravenous injection of human immunoglobulin and plasma exchange), and thymectomy. With the continuous deepening of research on MG treatment, targeted immune regulation of B cells, complement system, and neonatal Fc receptors has become a current research hotspot in the treatment of MG. Compared with traditional immunosuppressants, MG patients have better tolerance to new biological agents. This article elaborates on the research of MG targeted therapy related drugs and summarizes their efficacy and safety in MG treatment, aiming to find more treatment options.
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.
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.
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.
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.
Patients with coronavirus disease 2019 may have systemic symptoms of varying degrees. These symptoms are related to inflammatory response, massive release of pro-inflammatory cytokines and cytokine storm. In recent years, programmed necrosis, as a controllable type of necrosis, is considered to be an important factor that mediates inflammation. Recent studies have shown that programmed necrosis is involved in the inflammatory response and pulmonary fibrosis of coronavirus disease 2019. This article mainly reviews the mechanism of programmed necrosis, its participation in the occurrence and development of coronavirus disease 2019, and the research progress of programmed necrosis inhibitors in the treatment of coronavirus disease 2019, aiming to provide a certain basis for the diagnosis and treatment of coronavirus disease 2019.
Objective To observe the expression and investigate the significance of suppressor of cytokine signaling (SOCS) in peripheral blood mononuclear cells (PBMC) of experimental autoimmune uveitis (EAU). Methods 100 Lewis rats were immunized with interphotoreceptor retinoid-binding protein (IRBP) to induce EAU animal model, and they were divided into control group and treatment group randomly. The treatment group was administered cyclosporine A 20mg/（kgmiddot;d）after 1 to 28 days of immunization; the control group received saline buffer at equal quantity. All eyes were evaluated by slit-lamp microscopy before and after 7, 14, 21, 28 days of immunization; IL-4，IL-12，IFN-gamma; in the serum were measured by enzyme linked immunosorbent assay(ELISA); the SOCS mRNA and protein level in PBMC were measured by quantitative polymerase chain reaction (q-PCR) and western blot. Results The inflammation was most obvious at 14 days after immunization. The control group showed obvious iridocyclitis; the treatment group showed mild anterior chamber inflammation but no posterior synechia and hypopyon. The highest level of IL-12 and IFN-gamma; were observed at 14 days after immunization, followed by decline to the baseline at 28 days after immunization in control group; the highest level of IL-12 and IFN-gamma; were found at 14 days after immunization in treatment group, but the level was lower than control group obviously. Compared with the level before immunization, there are no differences at other time-point. The concentration of IL-4 decreased indistinctly in control group but increased in treatment group. SOCS1、Both of SOCS1 and SOCS5 increased to the highest level at 14 days after immunization, as 4.05 and 383 times of preimmunization in control group respectively, as 1.15 and 1.16 times in treatment group respectively. The CIS and SOCS3 mRNA increased lightly in two groups and treatment group milder than control group. Marked increased expression of SOCS1 and SOCS5 protein was detected at 7, 14, 21days than preimmunization, both of CIS and SOCS3 protein were significantly increased on 14, 21 days in control group; only SOCS1 protein was significantly increased on 14 days in treatment group and there are no differences at other time-point compared to pre-immunization. Conclusion Up-regulation of SOCS1 and SOCS5 expression maybe related to intensive response of Th1 in the development of EAU. Mild up-regulation of CIS and SOCS3 maybe associated with intensive response of Th2 which against the reaction of Th1 to carry out the dynamic immune balance.
Objective To study the effect of nontypeable Hemophilus influenzae(NTHi) strain ATCC49247 on proinflammatory cytokines expression of human A549 lung epithelial cell line. Methods Confluent A549 cells were co-incubated with NTHi, NTHi+Erythromycin(10 mg/L), NTHi+Gentamicin(100 mg/L), and NTHi+Dexamethasone(100 μmol/L),and nuclear factor kappa B(NF-κB) inhibitor primed cells were co-incubated with NTHi for 24 h. Then levels of interleukin-8（IL-8） and tumor necrosis factor-α(TNF-α) in the supernatant was assayed by enzyme-linked immunosorbent assay(ELISA) and the expression of intercellular adhesion molecule-1(ICAM-1) in cells was detected by immunohistochemistry staining. Results A549 cells were transformed and died after co-intubated with NTHi for 24 h. NTHi induced A549 cells to release significantly greater amounts of IL-8, which was inhibited by NF-κB inhibitor pyrrolidine dithiocarbamate（PDTC）. Incubating of A549 cells with NTHi significantly induced release of IL-8 and the expression of ICAM-1, which was blocked by erythromycin and dexamethasone and not by gentamicin. TNF-α was not detected in all circumstances. Conclusions NTHi can increase significantly the release and expression of proinflammatory cytokines through NF-κB pathway. Antibacterial drug erythromycin also has anti-inflammatory effect.