Objective To observe the effect of “Luo’s Roujin Technique” on the inflammatory response and joint capsule fibrosis in white rabbits with scapulohumeral periarthritis model. Methods Thirty healthy male New Zealand white rabbits were randomly divided into a control group, a model group, and a treatment group, with 10 rabbits in each group. Scapulohumeral periarthritis models were established in the model group and the treatment group, while the control group received identical restraint procedures at the same timepoints. Six rabbits in the model group and seven in the treatment group were successfully modeled. The subsequent experiment included all six successfully modeled rabbits from the model group, along with six rabbits randomly selected from each of the control and treatment groups. On the second day after successful modeling, blood samples were collected from the auricular marginal vein in all three groups. After blood collection, the treatment group began massage therapy for 21 consecutive days, while the other two groups underwent the same restraint procedure simultaneously. On Day 22, all the three groups were euthanized after blood collection from the auricular marginal vein, and the synovial tissue of the affected shoulder joint was completely collected. Hematoxylin-eosin staining was used to examine the histopathological features of the synovial tissue. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-α (TNF-α). Western blot and reverse transcription polymerase chain reaction were used to assess the protein and mRNA expression levels of vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), and Smad3. Results After treatment, the control group showed no significant inflammatory cell infiltration or fibrous tissue proliferation in the synovial tissue. The model group exhibited synovial cell hyperplasia in the lining layer and inflammatory cell infiltration in the sublining layer. The treatment group displayed mild inflammatory cell infiltration in the sublining layer. Compared with the control group, the model group showed significantly increased concentrations of IL-1β, IL-6, IL-17, and TNF-α in both serum and synovial homogenate, as well as elevated protein and mRNA expression of VEGF, CTGF, TGF-β1, and Smad3 in synovial tissue (P<0.05). Compared with the model group, the treatment group exhibited significantly lower serum levels of IL-1β, IL-6, and TNF-α, as well as reduced synovial homogenate levels of IL-1β, IL-6, IL-17, and TNF-α (P<0.05); furthermore, protein expression of VEGF, CTGF, TGF-β1, and Smad3 and mRNA expression of VEGF and CTGF in synovial tissue were significantly decreased in the treatment group (P<0.05). Conclusions “Luo’s Roujin Technique” can significantly alleviate local inflammatory infiltration in the synovial tissue of rabbits with scapulohumeral periarthritis, and reduce the levels of IL-1β, IL-6, IL-17, and TNF-α in both serum and synovial tissue. The underlying mechanism may involve suppression of VEGF, CTGF, TGF-β1, and Smad3 expression, leading to attenuated inflammatory responses and inhibition of fibroblast-to-myofibroblast transition. Thereby, it mitigates fibrotic changes in the shoulder joint capsule, exerting anti-inflammatory and analgesic effects and improving joint mobility.
A new independent subtype CD4+ T cell which massively secreted interleukin-17 (IL-17) was found at the beginning of the 21st century, and thus it was named as T helper cell 17 (Th17 cell). With the progress of the research in recent years, Th17 cells were found to be widely involved in a variety of the human diseases such as autoimmune diseases, infections and tumors through secretion of IL-17. The relationship between Th17 cells, IL-17 and the occurrence, development and prognosis of lung cancer was reviewed.
ObjectiveTo explore the application value of transoral snare traction in endoscopic submucosal dissection (ESD) for patients with early gastric cancer (EGC). MethodsA total of 90 EGC patients admitted to Xinxiang Central Hospital from January 2020 to April 2023 were selected and randomly divided into a study group and a conventional group using a random number table method. The conventional group was received ESD, while the study group was received transoral snare traction in combination with ESD. Baseline data, treatment efficacy, as well as the serum inflammatory-stress factors (tumor necrosis factor alpha, interleukin-6, adrenocorticotropic hormone, and cortisol) and gastrointestinal hormones (motilin and gastrin), surgical indicators, gastrointestinal function recovery indicators before surgery and on day 1 and 3 after surgery, postoperative complications, improvement in quality of life, and 2-year recurrence rate were compared between the two groups. The test level was set at α=0.05. ResultsThere were no statistically significant differences in age, gender, body mass index, disease duration, longest tumor diameter, lesion location, and tumor differentiation degree between the study group and the conventional group (P>0.05). The total effective rate in the study group was higher than that in the conventional group [95.6% (43/45) vs. 80.0% (36/45), χ2=5.075, P=0.024]. The results of repeated-measures ANOVA showed statistically significant between-group, time, and between-group-time interaction effects of serum inflammatory-stress factor and gastrointestinal hormone levels in the study and conventional groups (P<0.05), the effect of the time factor on inflammatory-stress factors and gastrointestinal hormones varied with intervention (P<0.001), postoperative inflammatory-stress factors levels in the study group exhibited aninitial increase followed by a decline, ultimately falling below those of the conventional group, the levels of serum motilin and gastrin in the study group continued to decrease than those before surgery and the reduction was smaller in the study group than in the control group. The operation duration, recovery of bowel sounds, the first exhaust, the first defecation, and the first meal time in the study group were shorter than those in the conventional group (P<0.05), and the intraoperative blood loss was less than that in the conventional group (P<0.05), the overall complication rate was lower than that in the conventional group [4.4% (2/45) vs. 17.8% (8/45), χ2=4.050, P=0.044], and the improvement rate in quality of life was higher than that in the conventional group [77.8% (35/45) vs. 57.8% (26/45), χ2=4.121, P=0.042]. There was no significant difference in the recurrence rate between the two groups after a 2-year follow-up [7.0% (3/43) vs. 17.1%(7/41), χ2=1.191, P=0.275]. ConclusionThe results of this study suggest that the treatment of early gastric cancer with transoral snare traction combined with ESD has significant efficacy, which can optimize surgical procedures, reduce inflammatory-stress reaction, improve gastrointestinal hormone levels, promote disease recovery, reduce the occurrence of complications, and achieve good short- and medium-term outcomes.
ObjectiveTo summarize the anti-inflammatory effects of irisin in inflammatory diseases.MethodThe relevant literatures at home and abroad in recent years were systematically searched and read to review the anti-inflammatory effects of irisin in the inflammatory diseases.ResultsThe irisin was widely distributed in the body and played a physiological role in inducing the browning of white adipocytes, improving energy metabolism and glucose utilization. A grow body of evidences demonstrated that the irisin exerted the anti-inflammatory effects by inhibiting increased pro-inflammatory cytokines and tumor necrosis factor-α, antagonizing apoptosis and activation of nuclear factor-κB, and improving tissue damage in many inflammatory diseases, such as acute lung injury, inflammatory bowel disease, septic cardiomyopathy, acute pancreatitis, nonalcoholic fatty liver disease, and malignant tumors.ConclusionsIrisin plays an important anti-inflammatory role in pathogenesis of inflammatory diseases. Irisin is considered as a promising candidate biomarker for diagnosis and prognosis of inflammatory diseases, and a novel target for treatment of inflammatory diseases.
Acute pancreatitis (AP) is a gastroenterological emergency with an acute onset and a high mortality rate. The main pathogenesis of AP is pancreatic damage and excessive activation of inflammatory cells induced by multiple factors. Due to anatomical features, the liver is the first extrapancreatic organ to be attacked by high concentrations of trypsin and inflammatory mediators during AP. Hepatic macrophages have been shown to be a major source of AP-related inflammatory factors. Interventions targeting hepatic macrophages may be critical to block liver injury/failure during AP, promote tissue repair, and reduce systemic symptoms. This review summarizes the pathological role of hepatic macrophages in AP and targeted interventions to provide new ideas and approaches to resolve the pathogenesis of AP and alleviate concurrent liver injury.
Objective To investigate the regulatory effects of SHP2 inhibition on the secretion of macrophage-associated inflammatory factors in KRAS-mutant lung cancer cells and to elucidate the underlying mechanisms by which this inhibition remodels the tumor immune microenvironment. Methods Three KRAS-mutant lung cancer cell lines were treated with the SHP2 inhibitor SHP099. The levels of phosphorylated SHP2 and ERK were assessed by Western blot. The expression levels of related inflammatory factors were analyzed using Luminex assay and qRT-PCR assay. Transcriptome sequencing was performed to identify differentially expressed genes and conduct KEGG pathway enrichment analysis. The expression of CXCL8 was validated by flow cytometry and Western blot. Survival analysis and gene set correlation analysis were conducted based on the TCGA database. Results SHP099 significantly inhibited the expression of p-SHP2 and p-ERK proteins, and reduced the secretion of multiple macrophage-related inflammatory factors. qRT-PCR confirmed a decrease in CXCL8 mRNA levels. Transcriptome analysis revealed significant enrichment of the rheumatoid arthritis pathway. Flow cytometry and Western blot validated a significant reduction in CXCL8 protein expression. Survival analysis showed that patients with KRAS-mutant lung adenocarcinoma and high CXCL8 expression had a shorter overall survival, and CXCL8 was positively correlated with M2 macrophage marker genes. Conclusion Targeted inhibition of SHP2 can suppress the expression of some macrophage-related inflammatory factors in KRAS-mutant lung cancer cells, with the most significant inhibition of CXCL8 expression. The mechanism may involve SHP2 regulating the transcription factor AP-1.
Objective To investigate the clinical significance of changes in cardiopulmonary function, degree of hypoxia and inflammatory factors in obstructive sleep apnea hypopnea syndrome (OSAHS) patients combined chronic obstructive pulmonary disease (COPD). Methods A retrospective case-control study was conducted on 209 patients with OSAHS admitted from October 2015 to April 2022. The OSAHS patients were divided into an OSAHS-only group, an OSAHS combined with mild COPD group, an OSAHS combined with moderate COPD group, and an OSAHS combined with severe and very severe COPD group based on pulmonary function test. The characteristics of cardiopulmonary function [(pulmonary artery pressure, N terminal pro B type natriuretic peptide (NT-proBNP), forced expiratory volume in the first second to forced vital capacity (FEV1/FVC), percent predicted value of FEV1 (FEV1%pred)], hypoxia indexes [night lowest saturation of pulse oxygen (NL-SpO2), night medial saturation of pulse oxygen (NM-SpO2), saturation of pulse oxygen less than 85% of the time (TS85), diurnal lowest saturation of pulse oxygen (DL-SpO2)], inflammatory factor indicators [procalcitonin (PCT), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), neutrophil to lymphocyte ratio (NLR)], and other characteristics were compared separately. The partial correlation analysis and logistic regression were used to analyze the influencing factors of OSAHS with COPD. Results There were statistically significant differences in age, days of hospitalization, cardiopulmonary function indexes, hypoxia indexes and inflammatory factor indexes between the OSAHS combined with COPD group and the OSAHS-only group (all P<0.05). And pulmonary artery pressure, NT-proBNP, TS85, IL-6, and NLR were higher and DL-SpO2, NL-SpO2, and NM-SpO2 were lower in the OSAHS combined with severe and very severe COPD group compared with the OSAHS combined with mild COPD group (all P<0.05). In the partial correlation analysis, FEV1%pred was negatively correlated with pulmonary artery pressure, NT-proBNP, TS85, IL-6, hs-CRP and NLR, and positively correlated with DL-SpO2, NL-SpO2 and NM-SpO2 (all P<0.05). In regression analysis, NLR and TS85 were the main risk factors for OSAHS combined with COPD (all P<0.05). Conclusions OSAHS patients combined with COPD have longer hospital days, greater burden of hypoxia, cardiopulmonary function and inflammation compared with patients with OSAHS alone, especially more significant in patients with poorer pulmonary function, and higher incidence of pulmonary heart disease, atrial fibrillation, and lower limb edema. NLR and TS85 are the main risk factors in patients with OSAHS combined with severe and very severe COPD.
Objective To investigate the protective effect of annexin A1 (ANXA1) derived from human umbilical cord mesenchymal stem cells (HucMSCs) on lipopolysaccharide (LPS) -induced acute lung injury (ALI). Methods Six-week-old male C57BL/6 mice were randomly divided into a sham group, a LPS group, a LPS+HucMSC-cm (LPS+cm) group, a LPS+nc-cm group, and a LPS+si-cm group, with 6 mice in each group. LPS (5 mg/kg) was intratracheally injected to induce ALI model. Then, normal saline, HucMSC-cm (HucMSC conditioned medium), HucMSC-nc-cm (normal ANXA1 expression) and HucMSC-si-cm (knockout of ANXA1) were injected intratracheally with 50 μL each after LPS treatment for 4 hours. After 72 hours of LPS administration, the mice were killed, and the blood and lung tissues were retained. After corresponding treatment, the blood and lung tissues were preserved. The expression of IL-6 in peripheral blood of mice was detected by enzyme-linked immunosorbnent assay, the pathological changes of lung tissues were observed by hematoxylin-eosin staining, and the expressions of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of each group were detected by Western blot and immunohistochemistry. Results Compared with the sham group, the lung histopathology of mice in the LPS group showed significantly increased inflammatory factor infiltration, alveolar collapse, and lung tissue structure destruction as well as lung tissue injury score and wet/dry weight ratio (W/D) increased (all P<0.05). Accordingly, IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased (all P<0.05). Compared with the LPS group, the pathological injury of lung tissue in the LPS+cm group was improved, the lung tissue injury score and the W/D ratio decreased while IL-6, VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were decreased (all P<0.05). But there were no significant differences between the LPS+cm group and the LPS+ nc-cm group (all P>0.05). Compared with the LPS+nc-cm group, lung tissue pathological injury was aggravated again, lung tissue injury score and W/D were also increased in the LPS+si-cm group (all P<0.05). IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased again (all P<0.05). Conclusion ANXA1 derived from HucMSCs has certain protective effect in LPS-induced ALI model.
Systemic inflammatory response (SIR) evoked by cardiopulmonary bypass (CPB) is still one of the major causes of postoperative multiple organs injuries. Since the concentrations of circulating inflammatory factors are positively associated with postoperative adverse events, removal or inhibition of inflammatory factors are considered as effective treatments to improve outcomes. After more than 20 years of research, however, the results are disappointed as neither neutralization nor removal of circulating inflammatory factors could reduce adverse events. Therefore, the role of circulating inflammatory factors in CPB-related organs injuries should be reconsidered in order to find effective therapies. Here we reviewed the association between circulating inflammatory factors and the outcomes, as well as the current therapies, including antibody and hemadsorption. Most importantly, the role of circulating inflammatory factors in SIR was reviewed, which may be helpful to develop new measures to prevent and treat CPB-related organs injuries.
ObjectiveTo explore the effect of preoperative glucocorticoid on systemic inflammatory indexes and pulmonary inflammation after radical esophagectomy.MethodsA total of 44 patients with esophageal cancer treated in the First Affiliated Hospital of Xiamen University from July 2019 to September 2020 were selected and randomly divided into an intervention group and an observation group by random number table. There were 22 patients in the intervention group, including 20 males and 2 females with an average age of 62.86±5.22 years and 22 patients in the observation group, including 19 males and 3 females with an average age of 63.00±6.19 years. Two groups were given thoracoscope-assisted incision via right chest, upper abdomen and left neck. The intervention group was given an intravenous infusion of methylprednisolone 500 mg before induction of anesthesia, and the observation group was given the same dose of normal saline. The second generation cephalosporins were routinely used to prevent infection in the two groups. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP), lymphocyte and neutrophil count before operation and 1 day, 3 days and 5 days after operation were recorded and compared between the two groups. Utrecht Pneumonia Scoring System (UPSS) score 1 day after operation, the healing of the surgical incision and the anastomotic leakage within 2 weeks after the operation were evaluated.ResultsThe level of IL-6 in the intervention group was significantly lower than that in the observation group at 1 hour and 1 day after operation (both P<0.05). CRP showed significant difference between the two groups 2 days after operation (P=0.044). The white blood cell count in the intervention group was significantly less than that in the observation group 1 day and 3 days after operation (both P<0.05). There was no significant difference in lymphocyte or neutrophil count between the two groups 1 day after operation. There was no significant difference in the rate of non-grade A wound healing or the incidence of anastomotic leakage between the two groups within 2 weeks after operation. The pneumonia score of UPSS in the intervention group was lower than that in the observation group 1 day after operation (P=0.027).ConclusionThe use of glucocorticoid before radical esophagectomy can reduce the systemic inflammatory reaction and improve the short-term postoperative pulmonary inflammation. At the same time, no adverse effect on the healing of surgical incision and anastomotic stoma is found, which has certain safety.