Effect of peripheral nerve block versus general anesthesia on the hemodynamics and prognosis of diabetic patients undergoing diabetic foot Surgery.

BACKGROUND: Diabetic foot ulcers (DFUs) represent a significant foot-related concern for patients with multiple co-morbidities, and surgical intervention is often employed. Notably, peripheral nerve block anesthesia (PNB) has emerged as a new approach for the surgical management of DFUs, providing sustained hemodynamic stability and superior postoperative pain control compared to general anesthesia (GEA). METHODS: The present study utilized a retrospective analysis of hospitalized patients who met the inclusion criteria for DFUs over a period of 7 years. Patients were categorized into two groups based on the type of anesthesia employed during the procedure: GEA or PNB. Extensive patient information was gathered and analyzed, such as demographics, intraoperative hemodynamic parameters, numeric rating scale (NRS) scores, and healing outcomes. The preliminary results assessed in this study were intraoperative hemodynamic stability and postoperative analgesic efficacy. RESULTS: During the study period, 117 patients received surgical therapy based on GEA, while 145 patients received PNB. Notably, the mean intraoperative blood pressure was significantly lower in the GEA group, and this difference remained statistically significant even after Bonferroni adjustment using linear mixed models. Additionally, the frequency of hypotensive episodes was higher in the GEA group (P < 0.05). Furthermore, the perioperative transfusion volume, overall intraoperative fluid input, and intraoperative bleeding volume were significantly more significant in the GEA group than in the PNB group. The postoperative pain NRS scores differed considerably between the two groups (Bonferroni corrected P < 0.01), with the GEA group exhibiting higher opioid consumption on the day of surgery and the first postoperative day when using patient-controlled intravenous analgesia (PCIA). Supplemental analgesic medication was more significant in the GEA group 24 h postoperatively. However, the two groups had no difference in hospital stay or treatment outcomes. There was no difference between the two groups regarding secondary surgery and amputation procedures. Although the 5-year mortality rate is 30.5%, no significant difference in mortality rates between the two groups was observed. CONCLUSIONS: Compared to GEA, PNB is a safe and effective alternative therapy for managing DFUs. Our findings suggest that PNB administration during surgical intervention for this condition results in more stable intraoperative hemodynamics and superior postoperative analgesic effects, despite no significant difference in overall treatment outcomes between the two groups. The two groups did not differ in re-surgery, amputation, or 5-year mortality.

Increased Metallothionein-1 Associated with Gout Activity and Tophi.

BACKGROUND AND AIMS: Gout is a chronic self-limiting inflammatory arthritis. An increase in metallothionein-1 (MT-1) has been reported in rheumatoid arthritis and osteoarthritis, and it attenuates inflammation and the pathology of diseases. This study aims to detect MT-1 levels in patients with gout and to explore its correlation with disease activity, clinical indexes, and inflammatory cytokines. METHODS: The expression of MT-1 messenger RNAs (mRNAs) and protein levels in patients with gout were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Correlations between MT-1 and clinical indexes or inflammatory mediators were analyzed using Spearman's correlation test. RESULTS: Compared with healthy controls (HCs, n = 43), patients with active gout (n = 27) showed higher levels of MT-1 mRNA in peripheral blood mononuclear cells and protein in serum, particularly those with tophi. No significant difference in serum MT-1 levels was observed among patients with inactive gout, HCs, and patients with hyperuricemia without gout. Furthermore, no significant difference was observed between patients with gout with kidney damage and HCs. In addition, serum interleukin (IL)-1ß, IL-6, and IL-8 levels were significantly increased in patients with active gout, particularly in those with tophi. The serum MT-1 level was positively correlated with C-reactive protein, as well as with IL-1ß, IL-6, and IL-18. CONCLUSION: The higher levels of MT-1 were found in patients with gout, which were correlated with disease activity and gout related pro-inflammatory cytokines. Indicating MT-1 may serve as a new marker for predicting disease activity.Abbreviations: IL-1ß: Interleukin 1ß; MT-1: Metallothionein-1; CRP: C-Reactive Protein; ROS: Reactive Oxygen Species; IL-10: Interleukin 10; TGF-ß: Transforming Growth Factor Beta.

Metallothionein-1 is Positively Correlated with Inflammation and Ankylosing Spondylitis Activity.

Introduction: Ankylosing spondylitis (AS) is a common form of chronic inflammatory rheumatic disease. Metallothionein-1 (MT-1) has been known to play an immunosuppressive role in various noninfectious inflammatory diseases, especially osteoarthritis and rheumatoid arthritis, thus inhibiting inflammation and pathogenesis in various diseases. However, whether MT-1 is related to AS is unclear. Here, we examined the levels of MT-1 in patients with AS and its correlation with the disease activity, complication, clinical indexes, and inflammatory cytokines and attempted to explain the effect of MT-1 on inflammation in AS. Methods: The messenger RNA (mRNA) and protein expression of MT-1 in patients with AS were detected through real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The associations between serum MT-1 protein level and clinical indexes or proinflammatory cytokines in AS were analyzed using the Spearman correlation test. Results: The mRNAs and serum protein levels of MT-1 were significantly higher in patients with AS, especially in patients with active AS and patients with osteoporosis (OP) than in healthy controls (HCs), and no difference was observed between patients with inactive AS and HCs. Serum MT-1 levels positively correlated with disease activity, proinflammatory cytokines, and clinical indexes Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein, C-reactive protein level, and erythrocyte sedimentation rate in patients with AS. Conclusion: MT-1 expression was upregulated in patients with active AS but not in those with inactive AS and positively correlated with clinical indexes, especially in OP, as well as with proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1ß, and IL-6 in patients with AS.

Interleukin-37 exacerbates experimental colitis in an intestinal microbiome-dependent fashion.

Background: Inflammatory bowel disease (IBD) involves complicated crosstalk between host immunity and the gut microbiome, whereas the mechanics of how they govern intestinal inflammation remain poorly understood. In this study, we investigated the contribution of environmental factors to shaping gut microbiota composition in colitis mice that were transgenic for human IL-37, a natural anti-inflammatory cytokine possessing pathogenic and protective functions related to microbiota alterations. Methods: Mice transgenic expressing human IL-37 (IL-37tg) were housed under conventional and specific pathogen-free (SPF) conditions to develop a mouse model of dextran sulfate sodium (DSS)-induced colitis. 16S ribosomal RNA sequencing was used for analyzing fecal microbial communities. The efficacy of microbiota in the development of colitis in IL-37tg mice was investigated after antibiotic treatment and fecal microbiota transplantation (FMT). The mechanism by which IL-37 worsened colitis was studied by evaluating intestinal epithelial barrier function, immune cell infiltration, the expression of diverse cytokines and chemokines, as well as activated signaling pathways. Results: We found that IL-37 overexpression aggravated DSS-induced colitis in conventional mice but protected against colitis in SPF mice. These conflicting results from IL-37tg colitis mice are ascribed to a dysbiosis of the gut microbiota in which detrimental bacteria increased in IL-37tg conventional mice. We further identified that the outcome of IL-37-caused colon inflammation is strongly related to intestinal epithelial barrier impairment caused by pathogenic bacteria, neutrophils, and NK cells recruitment in colon lamina propria and mesenteric lymph node to enhance inflammatory responses in IL-37tg conventional mice. Conclusions: The immunoregulatory properties of IL-37 are detrimental in the face of dysbiosis of the intestinal microbiota, which contributes to exacerbated IBD occurrences that are uncontrollable by the immune system, suggesting that depleting gut pathogenic bacteria or maintaining intestinal microbial and immune homeostasis could be a promising therapeutic strategy for IBD.

Metallothionein 1: A New Spotlight on Inflammatory Diseases.

MT1 has been demonstrated to be an essential stress protein in maintaining physiological balance and regulating immune homeostasis. While the immunological involvement of MT1 in central nervous system disorders and cancer has been extensively investigated, mounting evidence suggests that MT1 has a broader role in inflammatory diseases and can shape innate and adaptive immunity. In this review, we will first summarize the biological features of MT1 and the regulators that influence MT1 expression, emphasizing metal, inflammation, and immunosuppressive factors. We will then focus on the immunoregulatory function of MT1 on diverse immune cells and the signaling pathways regulated by MT1. Finally, we will discuss recent advances in our knowledge of the biological role of MT1 in several inflammatory diseases to develop novel therapeutic strategies.

Food antigens exacerbate intestinal damage and inflammation following the disruption of the mucosal barrier.

Food antigens are closely related to progression of inflammatory bowel disease; however, details of how they induce intestinal immune responses and causes intestinal inflammation is not yet clear. The present study aimed to examine the effects of oral collagen on the intestinal mucosa, and elucidate the mechanism of food antigen-induced enteritis. Here, we provide evidence that Aspirin (a mucosal-damaging agent) and type II collagen (CII; a food antigen) acted synergistically to disrupt the intestinal mucosal barrier, and increase intestinal permeability, which resulted in a large amount of CII entered into the lamina propria, where it interacted with the intestinal immune system, promoted intestinal inflammation, and shaped innate and adaptive immune reactions into Th1-dominant. The underlying mechanism of the CII-induced intestinal inflammation may associate with higher levels of Th1, TLR2 and TLR4, and lower levels of Th2 in the intestine of Aspirin + CII treated rats. The study indicate that compromised integrity of the intestinal barrier appears to be a prerequisite for CII-induced intestinal inflammation. The synergistic effect of food antigens and mucosal barrier injury is an important cause of intestinal inflammation. This new understanding the role of food antigen on intestinal inflammation will provide us with a new strategy for treatment and prevention of intestinal inflammation.

Comprehensive analysis and identification of key genes and signaling pathways in the occurrence and metastasis of cutaneous melanoma.

BACKGROUND: Melanoma is a malignant tumor of melanocytes, and the incidence has increased faster than any other cancer over the past half century. Most primary melanoma can be cured by local excision, but metastatic melanoma has a poor prognosis. Cutaneous melanoma (CM) is prone to metastasis, so the research on the mechanism of melanoma occurrence and metastasis will be beneficial to diagnose early, improve treatment, and prolong life survival. In this study, we compared the gene expression of normal skin (N), primary cutaneous melanoma (PM) and metastatic cutaneous melanoma (MM) in the Gene Expression Omnibus (GEO) database. Then we identified the key genes and molecular pathways that may be involved in the development and metastasis of cutaneous melanoma, thus to discover potential markers or therapeutic targets. METHODS: Three gene expression profiles (GSE7553, GSE15605 and GSE46517) were downloaded from the GEO database, which contained 225 tissue samples. R software identified the differentially expressed genes (DEGs) between pairs of N, PM and MM samples in the three sets of data. Subsequently, we analyzed the gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the DEGs, and constructed a protein-protein interaction (PPI) network. MCODE was used to seek the most important modules in PPI network, and then the GO function and KEGG pathway of them were analyzed. Finally, the hub genes were calculated by the cytoHubba in Cytoscape software. The Cancer Genome Atlas (TCGA) data were analyzed using UALCAN and GEPIA to validate the hub genes and analyze the prognosis of patients. RESULTS: A total of 134, 317 and 147 DEGs were identified between N, PM and MM in pair. GO functions and KEGG pathways analysis results showed that the upregulated DEGs mainly concentrated in cell division, spindle microtubule, protein kinase activity and the pathway of transcriptional misregulation in cancer. The downregulated DEGs occurred in epidermis development, extracellular exosome, structural molecule activity, metabolic pathways and p53 signaling pathway. The PPI network obtained the most important module, whose GO function and KEGG pathway were enriched in oxidoreductase activity, cell division, cell exosomes, protein binding, structural molecule activity, and metabolic pathways. 14, 18 and 18 DEGs were identified respectively as the hub genes between N, PM and MM, and TCGA data confirmed the expression differences of hub genes. In addition, the overall survival curve of hub genes showed that the differences in these genes may lead to a significant decrease in overall survival of melanoma patients. CONCLUSIONS: In this study, several hub genes were found from normal skin, primary melanoma and metastatic melanoma samples. These hub genes may play an important role in the production, invasion, recurrence or death of CM, and may provide new ideas and potential targets for its diagnosis or treatment.

Comparison between nitroglycerin and remifentanil in acute hypervolemic hemodilution combined with controlled hypotension during intracranial aneurysm surgery.

Allogenetic transfusion has long been considered to be a relatively safe and extremely effective blood transfusion treatment. However, acute hypervolemic hemodilution (AHH) combined with the remifentanil-induced controlled hypotension (CH) have rarely been examined. Herein, 40 intracranial aneurysm surgery patients were randomly divided into nitroglycerin group (A group, n=20) and remifentanil group (B group, n=20). During intracranial aneurysm surgery, MAP, HR, Hb, and Hct were recorded. SjvO2, PjvO2, SaO2, PaO2 were measured, and CaO2, Da-jvO2, CjvO2, CERO2, VADL were calculated. In addition, The venous blood samples were collected for determining PT, TT, APTT, FBG, VIII, VWF and electrolytes. The results show that HR in nitroglycerin group dramatically accelerated and HR in remifentanil group slowed at 30 minutes after hypotension and 5 minutes after aneurysm occlusion (P<0.01) after hypotension. Compared with A group, the SjvO2 and CjvO2 of B group increased significantly and the Da-jvO2 and CERO2 decreased significantly at T3, T4. In addition, There were no significant differences between after AHH and before AHH in two groups (P>0.05) on TT, PT, APTT, FIB, VIII, VWF, Na(+), Cl(-), K(+), Ca(2+). These results suggest that AHH combined with remifentanil-based CH significantly lowered cerebral metabolic rate of oxygen and had effects on blood coagulation without clinical hemorrhagic signs increased and had important clinical significance for blood conservation.