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Abstract Objectives: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. Data source: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. Summary of findings: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. Conclusions: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.
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Objective To analyze the application value of alpha-fetoprotein (AFP) and interleukin-6 (IL-6) in prognosis prediction of hepatitis B virus (HBV) associated liver failure. Methods A total of 135 patients with HBV-related liver failure who underwent treatment at the Infection Department of the Second People's Hospital of Yibin City from July 2020 to June 2022 were selected as the study subjects (observation group). Additionally, 100 patients who underwent physical examination in the hospital during the same period with normal indicators were selected as the control group. Serum levels of AFP and IL-6 were compared between the two groups. Factors influencing the prognosis of HBV-related liver failure were analyzed. Multiple logistic regression was used to analyze the risk factors affecting the prognosis of HBV-related liver failure patients. Results The levels of serum AFP and IL-6 in the control group were lower than those in the control group, and the difference was statistically significant (P10.0 pg/mL were risk factors affecting the prognosis of HBV-related liver failure. Conclusion Serum AFP and IL-6 can predict the prognosis of patients with HBV-related liver failure, which is worthy of clinical study.
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@#Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.
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@#The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol in individuals with asthma with and without post-COVID condition (PCC). The study was designed to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA. The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased (p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC. However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r = -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683), but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age, IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma. Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main influence of asthma on the overall inflammatory response. These findings reveal a complex interplay between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.
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Objective@#To investigate the changes in the levels of interleukin-6 (IL-6) and let-7e in rats induced by coal mine dust, so as to provide the basis for the mechanism of coal worker's pneumoconiosis (CWP).@*Methods@#Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group, coal dust group, mixed dust group (mixed coal and silica dust) and quartz group. The rats in the control group were exposed to 1 mL physiological saline by non-exposure tracheal perfusion, and the rats in the dust-exposed groups were exposed to 1 mL dust suspension. Rats were sacrificed by anesthesia after 1 month and 6 months, lung tissue was observed using hematoxylin-eosin staining, the pathological change in the lungs was scored using the Szapiel scoring system, the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay, and the expression of let-7e was determined by quantitative real-time PCR.@*Results@#A month after exposure, a small amount of coal spots and inflammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group. The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum. Six months after exposure, there were more coal spots and slightly thickened alveolar septum in the coal dust group, and hyperplasia of pulmonary interstitial fibers, destruction of alveolar structure and silica nodules were observed in the mixed dust group. In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and silica nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P<0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust-exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05).@*Conclusions@#Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.
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ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.
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ObjectiveTo investigate the application value of Qingre Huashi Sanjie enema prescription in the treatment of the patients with sequelae of pelvic inflammatory disease (syndrome of combined dampness,heat,and stasis) and the effects of this prescription on inflammatory mediators and T lymphocyte subsets. MethodThe patients with sequelae of pelvic inflammatory disease (syndrome of combined dampness,heat,and stasis) treated from May 2022 to August 2023 were included in this study and randomized into two groups (79 cases). The control group was treated with conventional Western medicine,and the observation group was treated with Qingre Huashi Sanjie enema prescription on the basis of the therapy in the control group. Both groups were treated for 12 weeks. The serum levels of monocyte chemoattractant protein-1 (MCP-1),transforming growth factor-β1 (TGF-β1),and interleukin-6 (IL-6) were measured by enzyme linked immunoserbent assay (ELISA) before and after treatment in both groups. The erythrocyte sedimentation rate (ESR) and fibrinogen (FIB) were measured by an automatic blood rheology analyzer before and after treatment in both groups. The serum levels of CD4+,CD4+/CD8+ before and after treatment in both groups were measured by flow cytometry. The traditional Chinese medicine (TCM) symptom score and the 36-item short form survey (SF-36) score were assessed before and after treatment. The uterine artery resistance index (RI),uterine artery pulsatility index (PI),and uterine artery peak systolic velocity (PSV) were measured by Doppler before and after treatment. The clinical efficacy and the occurrence of adverse reactions were compared between the two groups. ResultAfter treatment,the levels of MCP-1,TGF-β1,IL-6,ESR,and FIB decreased in both groups (P<0.01),and the decreases were larger in the observation group than in the control group (P<0.05,P<0.01). After treatment,the serum levels of CD4+ and CD4+/CD8+ elevated in both groups (P<0.01) and the observation group had higher levels of CD4+ and CD4+/CD8+ than the control group (P<0.05,P<0.01). The treatment in both groups decreased the TCM symptom score and TCM sign score and increased the SF-36 score (P<0.01),and the changes were more significant in the observation group than in the control group (P<0.05,P<0.01). In addition,the treatment lowered RI and PI and elevated PSV (P<0.01),and the changes in these indicators were more significant in the observation group than in the control group (P<0.01). The total response rate in the observation group was 93.67% (74/79),which was higher than that (79.75%,63/79) in the control group (χ2=6.645,P<0.05). There was no significant difference in the occurrence of adverse reactions between the two groups. ConclusionFor the patients with sequelae of pelvic inflammatory disease (syndrome of combined dampness,heat,and stasis),Qingre Huashi Sanjie enema prescription can reduce inflammation,attenuate hypercoagulability,improve hemodynamics,and regulate the immune function,demonstrating a definite therapeutic effect.
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Abstract Background Glomus Tumor (GT) are benign neoplasms that originate from mesenchymal cells. It presents as tenderness and cold allodynia in the digits, especially in the subungual region. There are a few studies that investigated the mechanism of pain. Objectives To analyze the clinical-pathologic characteristics of GT and to identify the expression of IL-1β, IL-6, and CGRP in it, further, to explore the possible mechanism of pain. Methods The clinical and pathological data of 60 GT patients were retrospectively analyzed. Tissue microarrays and immunohistochemistry were used to measure the expression of IL-1β, IL-6 and CGRP. Results GT is more common in females and the ratio of male to was near to 1:2, mostly in middle-aged people. It often occurs in fingertips, especially the thumbs. Patients often present with spontaneous pain, tenderness, and cold hypersensitivity. Both the two pain mediators IL-1β and IL-6 were highly expressed in GT cells of patients with and without cold hypersensitivity. While CGRP was not expressed in GT. Study limitations Low sample size and further research is needed to explore the specific mechanism. Conclusions IL-1β and IL-6 were highly expressed in GT cells, suggesting that IL-1β and IL-6 have certain nociceptive roles in GT. In the 4 patients with cold intolerance, the intensity of IL-1β and IL-6 staining was also strong, suggesting that they may not play a role in the cold hypersensitivity. However, since there are only 4 patients with cold intolerance, it's necessary to conduct further in-depth research using a larger sample size. The specific role of CGRP in GT has not been found yet.
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ObjectiveTo investigate the value of L3 skeletal muscle index (L3-SMI) combined with interleukin-6 (IL-6) and activin A in predicting early-stage pancreatic cancer cachexia. MethodsA total of 74 patients with pancreatic cancer who were diagnosed in Hebei Medical University Forth Hospital from July 2020 to July 2023 were enrolled, and according to the presence or absence of cachexia after admission, the patient were divided into cachexia group with 58 patients and non-cachexia group with 16 patients. The levels of L3-SMI, IL-6, and activin A were observed within 48 hours after admission. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for pancreatic cancer cachexia; the receiver operating characteristic (ROC) curve was used to analyze the value of L3-SMI, IL-6, and activin A alone or in combination in predicting pancreatic cancer cachexia, and the Z test was used for comparison of the area under the ROC curve (AUC). ResultsCompared with the non-cachexia group, the cachexia group had a significantly higher level of L3-SMI and significantly lower serum levels of IL-6 and activin A (t=8.649, 3.049, and 8.100, all P<0.05). The multivariate logistic analysis showed that L3-SMI (odds ratio [OR]=0.266, 95% confidence interval [CI]: 0.103 — 0.683, P<0.05), serum IL-6 (OR=4.158, 95%CI: 1.368 — 12.333, P<0.05), and activin A (OR=5.124, 95%CI: 1.550 — 16.939, P<0.05) were influencing factors for pancreatic cancer cachexia. L3-SMI, IL-6, and activin A alone had a significantly lower AUC than the combination of the three indicators in predicting pancreatic cancer cachexia (0.851/0.752/0.791 vs 0.946, Z=-2.841, -2.552, and -2.647, all P<0.001), and the combination of the three indicators had the highest sensitivity (90.9%), specificity (87.8%) and Youden index (0.788). ConclusionL3-SMI combined with serum IL-6 and activin A has a good value in predicting early-stage pancreatic cancer cachexia.
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Objective To investigate the therapeutic effects and mechanisms of Maxing Shigan Decoction on cough variant asthma(CVA)rats.Methods Sixty rats were randomly divided into normal group,model group,low and high dose groups of Maxing Shigan Decoction,and high-dose of Maxing Shigan Decoction + signal transducer and activator of transcription 3(STAT3)activator Colivelin(Col)group,12 rats in each group.Except for the normal group,the CVA model was constructed by intraperitoneal injection of ovalbumin combined with moxa fumigation in all other groups of rats.After the corresponding treatment,the rats were observed for signs and cough counts,airway resistance(RE)was detected by pulmonary function meter,eosinophils(EOS)were counted by Diff-Quik staining,histopathological features of the lungs and bronchial tubes were observed by hematoxylin-eosin(HE)staining method,and the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA)for monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α),and the protein expression levels of interleukin 6(IL-6),STAT3,and transient receptor potential vanilloid-1 channel(TRPV1)were detected by Western Blot.Results Compared with the normal group,rats in the model group showed obvious asthma symptoms,severe inflammatory cell infiltration was seen in the lung tissue,bronchial epithelial cell necrosis,ciliated adhesion,mucus,and RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,TRPV1 were elevated(P<0.05);compared with the model group,rats in the low-and high-dose groups of Maxing Shigan Decoction showed significant improvement in asthma symptoms,reduction in lung and bronchial injury,and dose-dependent reduction in RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P<0.05);compared with the high-dose group of Maxing Shigan Decoction,the rats in the high-dose Maxing Shigan Decoction+Col group showed increased asthma,increased lung and bronchial injury,and increased RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P<0.05).Conclusion Maxing Shigan Decoction can effectively improve cough variant asthma in rats,and its mechanism is related to the inhibition of IL-6/STAT3 signaling pathway and the high expression of TRPV1.
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BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.
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BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.
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BACKGROUND:Molecular mechanisms targeting the miRNA/mRNA axis to regulate osteoarthritis disease process have been studied.We identified the mRNA:phospholipase C delta 3(PLCD3)and its target miRNA(miR-34a-5p)with clinical predictive value through previous bioinformatics studies,while experiments to verify their specific roles and mechanisms in regulating osteoarthritis are still lacking. OBJECTIVE:To investigate the regulatory role and mechanism of miR-34a-5p/PLCD3 axis on osteoarthritis progression. METHODS:The synovium of 15 patients with knee osteoarthritis was selected as the osteoarthritis group,and the synovium of 15 young patients with internal fixation of patellar fracture caused by trauma during the same period was selected as the control group.The expression of PLCD3 and miR-34a-5p in the synovium was detected by real-time PCR.Human fibroblast like synovial cells-osteoarthritis(HFLS-OA)cells were treated by cell transfection and divided into miR-34a-5p mimic group,pCDH-PLCD3 group,miR-34a-5p mimic+pCDH-PLCD3 group,miR-34a-5p inhibitor group,si-PLCD3 group,and miR-34a-5p inhibitor+si-PLCD3 group.The relationship between PLCD3 and miR-34a-5p expression was detected by real-time PCR.The effects of HFLS-OA cell viability and cell migration in each group were detected by CCK-8 assay and cell scratch test.Western blot assay was used to detect the expression level of apoptosis marker protein.The expression of inflammatory factors was detected by ELISA. RESULTS AND CONCLUSION:(1)PLCD3 was a direct target of miR-34a-5p,and the expression levels of PLCD3 and miR-34a-5p were negatively correlated.(2)Upregulation of PLCD3 promoted proliferation of HFLS-OA cells and inhibited cell migration.The up-regulation of miR-34a-5p significantly inhibited the activity of HFLS-OA cells and enhanced cell migration.Overexpression of miR-34a-5p significantly increased the levels of Casp3 and Casp9 proteins in HFLS-OA cells,while overexpression of PLCD3 showed the opposite trend.(3)PLCD3 overexpression significantly increased the expression of interleukin 6 and tumor necrosis factor alpha in HFLS-OA cells,while miR-34a-5p mimics showed protective activity.(4)The miR-34a-5p/PLCD3 axis may affect the progression of osteoarthritis by regulating the inflammatory process or apoptosis of synovial cells.
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BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.
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BACKGROUND:Unicompartmental knee arthroplasty has been paid more and more attention because of its advantages of fewer traumas,less blood loss,less complications,faster recovery,excellent knee function and high prosthetic survival rate.Most of the relevant reports focused on its clinical effect,but the changes in the levels of relevant inflammatory cytokines in patients after unicompartmental knee arthroplasty were rarely reported. OBJECTIVE:To investigate the effect of unicompartmental knee arthroplasty in patients with medial compartment osteoarthritis of the knee and the changes of interleukin-1,interleukin-6,and tumor necrosis factor-α levels. METHODS:A total of 30 patients with medial compartment osteoarthritis of the knee who received unicompartmental knee arthroplasty from September 2021 to March 2023 and met the inclusion criteria were selected as the study subjects.Medial angle of proximal tibia,femoral and tibial angle,pain visual analog scale score,hospital for special surgery score,knee joint range of motion,synovial fluid interleukin-1,interleukin-6,and tumor necrosis factor-α levels before and after surgery were compared and statistically analyzed. RESULTS AND CONCLUSION:(1)All 30 patients had grade I wound healing.All patients were followed up for more than 6 months after surgery.There were no complications such as prosthesis loosening and dislocation of prosthesis liner in all patients.(2)The medial proximal tibia angle and the femoral and tibial angles measured after operation were significantly improved(P<0.05).(3)The visual analog scale score,hospital for special surgery score and range of motion measured at 1,3,and 6 months after operation were better than those before operation(P<0.05),and showed a gradual improvement(P<0.05).(4)The levels of interleukin-1,interleukin-6,and tumor necrosis factor-α in synovial fluid at 3 and 6 months after operation were decreased gradually compared with those before operation(P<0.05)and showed a gradual downward trend at each time point after operation.(5)It is indicated that unicompartmental knee arthroplasty can effectively treat medial compartment osteoarthritis of the knee,significantly relieve pain,restore knee joint function,improve knee varus deformity and lower limb strength line,and reduce the levels of inflammatory cytokines interleukin-1,interleukin-6,and tumor necrosis factor-α in joints to a certain extent.
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Objective To investigate the predictive value of lactate/albumin ratio(LAR),interleukin-6(IL-6)and CD4+T lymphocyte count in 28-day mortality in patients with severe pneumonia and sepsis.Methods A total of 73 patients with severe pneumonia and sepsis admitted to the Respiratory Intensive Care Unit(RICU)of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2022 to June 2023 were enrolled and divided into the survival group(n=43)and the death group(n=30)according to their 28-day outcomes.The clinical data of the patients were collected from their electronic medical records,including age,gender,comorbidities with hypertension,diabetes,and coronary artery heart disease(CHD),as well as sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,mean arterial pressure(MAP),confusion,uremia,respiratory rate,blood pressure,age ≥65 years(CURB-65)score,total bilirubin(Tbil),serum creatinine(Scr),platelet count(PLT),white blood cell(WBC)count,procalcitonin(PCT),and C-reactive protein(CRP)at admission to RICU.On the 1st,3rd,and 7th day after admission to RICU,the patients'arterial blood was drawn,and the lactate level was detected by a fully automated blood gas analyzer.The peripheral venous blood was drawn,and the serum albumin and IL-6 levels were detected by enzyme-linked immunosorbent assay,and the CD4+T lymphocyte subset count was measured by flow cytometry.The LAR of patients on the 1st,3rd and 7th day was calculated.The clinical data of the patients and the LAR,IL-6 level and CD4+T lymphocyte count on the 1st,3rd,and 7th day were compared between the two groups.The influencing factors of 28-day mortality in patients with severe pneumonia and sepsis were analyzed by logistic regression,and the predictive value of each influencing factor on the 28-day mortality in patients with severe pneumonia and sepsis was evaluated by the receiver operating characteristic(ROC)curve.Results There was no significant difference in gender,age,proportions of comorbidities with hypertension,diabetes and CHD,length of stay in RICU,and Tbil,MAP,PLT,Scr,WBC,PCT and CRP at admission to RICU(P>0.05).The APACHE Ⅱ and CURB-65 scores of the patients in the death group were significantly higher than those in the survival group(P<0.05).On the 1st,3rd and 7th day,the CD4+T lymphocyte count in the death group was significantly lower than that in the survival group,while the SOFA score was significantly higher than that in the survival group(P<0.05).On the first day,there was no significant difference in the LAR and IL-6 level be-tween the death group and the survival group(P>0.05).However,on the 3rd and 7th day,the LAR and IL-6 level in the death group were significantly higher than those in the survival group(P<0.05).The LAR,IL-6 level and SOFA score on the 3rd and 7th day in the survival group were significantly lower than those on the 1st day,and these indicators on the 7th day were sig-nificantly lower than those on the 3rd day(P<0.05);the CD4+T lymphocyte count on the 3rd and 7th day was significantly higher than that on the 1st day(P<0.05),while it showed no significant difference on the 7th and 3r day(P>0.05).The IL-6 level on the 7th day in the death group was significantly lower than that on the 1st and 3rd day(P<0.05),while there was no significant difference in IL-6 level on the 1st day compared with the 3r day(P>0.05);moreover,there was no significant difference in LAR,CD4+T lymphocyte count and SOFA score between each time point(P>0.05).Pearson correlation analy-sis showed that on the 3rd day,the LAR and IL-6 level were significantly positively correlated with the SOFA score in patients with severe pneumonia and sepsis(r=0.385,0.394;P<0.05).On the 7th day,the LAR and IL-6 level were also significantly positively correlated with the SOFA score(r=0.418,0.402;P<0.05).On the 3 rd and 7 th day,CD4+T lymphocyte count was significantly negatively correlated with the SOFA score(r=-0.451,-0.454;P<0.05).Logistic regression analysis showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day,and the IL-6 level and CD4+T lym-phocyte count on the 7th day were the influencing factors for 28-day mortality in patients with severe pneumonia and sepsis(P<0.05).The ROC curve showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day and the combination of the three,IL-6 level and CD4+T lymphocyte count on the 7th day and the combination of the two had certain predictive value for the 28-day mortality in patients with severe pneumonia and sepsis(P<0.05).The area under the ROC curve(AUC)of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day combined to predict 28-day mortality in patients with severe pneumonia and sepsis was 0.891,and the AUC of APACHE Ⅱ score for predicting 28-day mortality in pa-tients with severe pneumonia and sepsis was 0.769.The AUC values of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.795,0.757 and 0.770,respective-ly,and the AUC values of IL-6 level and CD4+T lymphocyte count on the 7th day and their combination for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.743,0.802 and 0.888,respectively.Conclusion The 3-day LAR,IL-6 level and CD4+T lymphocyte count,and the 7-day IL-6 level and CD4+T lymphocyte count after admission are re-lated to the 28-day mortality in patients with severe pneumonia and sepsis.The combined LAR,IL-6 level and CD4+T lympho-cyte count on the 3rd day can better assess the severity and prognosis of patients.
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Objective:To evaluate the clinical efficacy of rituximab injection combined with CHOP regimen (cyclophosphamide+doxorubicin+vincristine+prednisolone) in the treatment of diffuse large B-cell lymphoma (DLBCL).Methods:One hundred and twenty patients with DLBCL who treatment in the First Affiliated Hospital of Xinjiang Medical University from June 2019 to June 2022 were selected as the study object. They were randomly divided into the study group (60 cases) and the control group (60 cases). The control group was treated with CHOP regimen, and the study group was treated with rituximab injection on the basis of CHOP regimen. The clinical efficacy, inflammatory reaction, immune function and adverse reaction were evaluated after 6 courses of treatment.Results:After treatment, the total clinical effective rate in the study group was higher than that in the control group: 88.33%(53/60) vs. 70.00%(42/60), there was statistical difference ( χ2 = 6.11, P<0.05). Before treatment, the levels of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IL-6 and TNF-α were decreased, and the levels of serum IL-6 and TNF-α in the study group were lower than those in the control group: (223.56 ± 21.28) ng/L vs. (267.35 ± 25.36) ng/L, (9.34 ± 2.75) μg/L vs. (11.96 ± 3.83) μg/L, there were statistical differences ( P<0.05). Before treatment, the levels of serum immunoglobulin (Ig) A, IgM and IgG in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IgA, IgM and IgG were decreased, but the levels of serum IgA, IgM and IgG in the study group were higher than those in the control group: (1.83 ± 0.46) g/L vs. (1.34 ± 0.34) g/L, (1.15 ± 0.22) g/L vs. (0.83 ± 0.24) g/L, (10.67 ± 1.65) g/L vs. (8.02 ± 1.62) g/L, there were statistical differences ( P<0.05). After treatment, the incidence of thrombocytopenia, leucopenia, gastrointestinal reaction, bone marrow suppression and liver function injury in the study group were lower than those in the control group: 6.67%(4/60) vs. 20.00%(12/60), 15.00%(9/60) vs. 31.67%(19/60), 30.00%(18/60) vs. 58.33%(35/60), 5.00%(3/60) vs. 16.67%(10/60), 10.00%(6/60) vs. 25.00%(15/60), there were statistical differences ( χ2 = 4.62, 4.66, 9.77, 4.33, 4.88, P<0.05). Conclusions:The treatment effect of rituximab injection combined with CHOP regimen in DLBCL is significant, which can reduce the inflammatory reaction of the body, reduce the damage of immune function, and reduce the adverse reactions of chemotherapy.
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Objective:To investigate the clinical efficacy of ginkgo ketone ester dropping pills combined with agatroban injection in the treatment of acute cerebral infarction.Methods:This prospective case-control study was conducted on 120 patients with acute cerebral infarction who were treated at The Hospital of Shanxi University of Chinese Medicine between April 2020 and April 2022. These patients were randomly divided into a control group and a study group using the random number table method, with 60 patients in each group. The control group received intravenous injections of agatroban based on conventional treatment, while the study group received treatment with ginkgo ketone ester dropping pills combined with agatroban injection based on conventional treatment. The treatment duration was 2 weeks. Clinical efficacy was evaluated after continuous treatment for 2 weeks.Results:The overall response rate in the study group was 95.0% (57/60), which was significantly higher than 80.0% (48/60) in the control group ( χ2 = 6.17, P = 0.012). After treatment, the Barthel index in the study group was (65.3 ± 7.3) points, which was significantly higher than (59.8 ± 7.5) points in the control group ( t = -4.07, P < 0.001). The modified Rankin Scale score and the National Institutes of Health Stroke Scale score in the study group were (1.2 ± 0.4) points and (4.6 ± 0.7) points, which were significantly lower than (2.4 ± 0.6) points and (7.6 ± 1.1) points, respectively, in the control group ( t = 12.89, 17.82, both P < 0.001). Interleukin-6, hypersensitive C-reactive protein, and tumor necrosis factor-α levels in the study group were significantly lower than those in the control group ( t = 10.10, 18.25, 14.15, all P < 0.001). The nitric oxide levels in the study group were significantly higher than those in the control group, while endothelin 1 and thromboxane A2 levels in the study group were significantly lower than those in the control group ( t = -7.65, 10.77, 21.90, all P < 0.001). There was no significant difference in incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:The combination of ginkgo ketone ester dropping pills and agatroban injection has a remarkable therapeutic effect on acute cerebral infarction. The combined therapy can reduce the severity of neurological deficits in patients, promote brain function recovery, improve quality of life, adjust serum inflammatory factors, and thereby be worthy of clinical application.
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Objective:To investigate the clinical effect of endoscopic injection of norepinephrine on cerebral infarction complicated by stress-induced gastrointestinal bleeding.Methods:A total of 150 patients with cerebral infarction complicated by stress-induced gastrointestinal bleeding who were admitted to the Intensive Care Unit of Lishui City People's Hospital from October 2020 to October 2021 were included in this study. These patients were randomly divided into a control group and an observation group using the random number table method, with 75 patients in each group. Patients in the control group received routine clinical treatment, while those in the observation group received endoscopic injection of norepinephrine in addition to routine clinical treatment. The hemostatic time, blood transfusion volume, and length of hospital stay were compared between the two groups. The stress index and inflammatory index were compared between the two groups before and after treatment. The hemostatic effect and adverse reactions were evaluated in each group.Results:The hemostatic time, blood transfusion volume, and length of hospital stay in the observation group were (16.16 ± 4.36) hours, (385.35 ± 41.28) mL, and (5.35 ± 1.28) days, respectively, which were significantly shorter or less than (27.27 ± 6.34) hours, (447.07 ± 32.07) mL, and (7.07 ± 2.07) days in the control group ( t = 12.50, 10.22, 6.12, all P < 0.001). After treatment, the levels of cortisol, norepinephrine, antidiuretic hormone, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α in the observation group were (288.33 ± 19.53) mmol/L, (29.17 ± 4.26) μg/L, (4.08 ± 1.08) mU/L, (38.27 ± 8.72) ng/L, (6.69 ± 1.35) μg/L, and (6.37 ± 1.51) mg/L, respectively, which were significantly lower than (327.22 ± 22.01) mmol/L, (39.32 ± 5.54) μg/L, (5.36 ± 1.22) mU/L, (51.24 ± 13.23) ng/L, (8.67 ± 2.29) μg/L, and (11.44 ± 3.13) mg/L in the control group ( t = 11.44, 12.57, 6.80, 7.08, 6.45, 12.63, all P < 0.001). The overall response rate of hemostasis in the observation group was 94.67% (71/75), which was significantly higher than 82.67% (62/75) in the control group ( χ2 = 5.37, P < 0.05). The incidence of adverse reactions in the observation group was 8.00% (6/75), which was slightly, but not significantly, lower than 14.67% (11/75) in the control group ( χ2 = 1.66, P > 0.05). Conclusion:Endoscopic injection of norepinephrine for the treatment of cerebral infarction complicated by stress-induced gastrointestinal bleeding can rapidly stop bleeding, effectively reduce inflammation,improve stress index, and be highly safe.
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Objective:To investigate the clinical efficacy of Danggui Shaoyao powder combined with folic acid tablets in the treatment of chronic atrophic gastritis. Methods:A total of 90 patients with chronic atrophic gastritis who were treated at Longyou Branch, Sir Run Run Shaw Hospital, Zhejiang University from March 2021 to March 2022 were included in this study. They were randomly divided into a control group and an experimental group, with 45 patients per group. The control group was treated with folic acid tablets, while the experimental group was treated with Danggui Shaoyao powder combined with folic acid tablets. Before and after treatment, traditional Chinese medicine syndrome scores, gastroscopy and pathology scores, and inflammatory factor levels were compared between the two groups. Clinical efficacy was compared between the two groups. Results:The amplitudes of decreases in traditional Chinese medicine syndrome score in the experimental group [acid reflux (0.57 ± 0.19) points and epigastric pain (0.84 ± 1.36) points] were significantly greater than those in the control group [acid reflux (1.46 ± 0.39) points, epigastric pain (1.52 ± 1.41) points, t = 4.86, 6.52, both P < 0.05]. Inflammatory factor levels in the experimental group [tumor necrosis factor-α (1.03 ± 0.11) μg/L, interleukin-6 (8.15 ± 1.42) ng/L, C-reactive protein (6.55 ± 0.98) mg/L] were significantly lower than those in the control group [tumor necrosis factor-α (1.73 ± 0.14) μg/L, interleukin-6 (12.24 ± 1.48) ng/L, C-reactive protein (10.23 ± 1.03) mg/L, t = 4.52, 7.66, 6.95, all P < 0.05]. The gastroscopy and pathological scores in the experimental group [intestinal metaplasia (0.78 ± 0.35) points, dysplasia (0.30 ± 0.10) points] were significantly lower than those in the control group [intestinal metaplasia (1.31 ± 0.38) points, dysplasia (0.68 ± 0.12) points, t = 4.13, 3.85, both P < 0.05]. The overall response rate in the experimental group was 93.33% (42/45), which was significantly higher than 77.78% (35/45) in the control group ( χ2 = 4.40, P < 0.05). Conclusion:Danggui Shaoyao powder combined with folic acid tablets in the treatment of chronic atrophic gastritis can effectively improve traditional Chinese medicine syndromes, reduce the level of inflammatory factors, and have a good clinical effect.