Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery

BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

Yeast hydrolysate attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage in weaned piglets

Background Intestinal inflammation is the main risk factor causing intestinal barrier dysfunction and lipopolysaccharide(LPS)can trigger inflammatory responses in various eukaryotic species.Yeast hydrolysate(YH)possesses multibiological effects and is received remarkable attention as a functional ingredient for improving growth performance and promoting health in animals.However,there is still inconclusive on the protective effects of dietary YH supplementation on intestinal barrier of piglets.This study was conducted to investigate the attenuate effects of YH supplementation on inflammatory responses and intestinal barrier injury in piglets challenged with LPS.Methods Twenty-four piglets(with an average body weight of 7.42±0.34 kg)weaned at 21 days of age were randomly assigned to one of two dietary treatments(12 replications with one pig per pen):a basal diet or a basal diet containing YH(5 g/kg).On the 22nd d,6 piglets in each treatment were intraperitoneally injected with LPS at 150μg/kg BW,and the others were injected with the same amount of sterile normal saline.Four hours later,blood samples of each piglet were collected and then piglets were euthanized.Results Dietary YH supplementation increased average daily feed intake and average daily gain(P<0.01),decreased the ratio of feed intake to gain of piglets(P sponse,evidenced by the increase o=0.048).Lipopolysaccharide(LPS)injection induced systemic inflammatory ref serum concentrations of haptoglobin(HP),adrenocorticotropic hormone(ACTH),cortisol,and interleukin-1β(IL-1β).Furthermore,LPS challenge resulted in inflammatory intestinal damage,by up-regulation of the protein or mRNA abundances of tumor necrosis factor-α(TNF-α),IL-1β,toll-like receptors 4(TLR4)and phosphor-nuclear factor-κB-p65(p-NFκB-p65)(P<0.01),and down-regulation of the jejunal villus height,the protein and mRNA abundances of zonula occludens-1(ZO-1)and occludin(OCC;P<0.05)in jejunal mucosa.Dietary YH supplementation decreased the impaired effects of ACTH,cortisol,HP,IL-1βand diamine oxidase in serum(P<0.05).Moreover,YH supplementation also up-regulated the jejunal villus height,protein and mRNA abundances of ZO-1 and OCC(P<0.05),down-regulated the mRNA expressions of TNF-αand IL-1βand the protein abundances of TNF-α,IL-1β,TLR4 and p-NFκB-p65 in jejunal mucosa in LPS-challenged pigs(P<0.01).Conclusion Yeast hydrolysate could attenuate inflammatory response and intestinal barrier injury in weaned piglets challenged with LPS,which was associated with the inhibition of TLR4/NF-κB signaling pathway activation.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Improvement of inflammatory response and gastrointestinal function in perioperative of cholelithiasis by Modified Xiao-Cheng-Qi decoction

BACKGROUND In the perioperative period of biliary surgery,various factors can induce the release of a large number of inflammatory factors,leading to an imbalance in proinflammatory and anti-inflammatory responses and resulting in gastrointestinal(GI)dysfunction.Enhanced Recovery After Surgery protocols in biliary surgery have been shown to reduce the stress response and accelerate postoperative recovery.It is crucial to reduce the inflammatory response and promote the recovery of GI function after biliary surgery,both of which are the basis and key for perioperative care and postoperative recovery.AIM To better understand the effects of Modified Xiao-Cheng-Qi decoction(MXD)on inflammatory response and GI function in the perioperative management of cholelithiasis and their correlation.METHODS This was a prospective randomized placebo-controlled trial,in which 162 patients who received biliary tract surgery were randomly assigned to three groups:MXD group,XD group,and placebo-control group.The observed parameters included frequency of bowel sounds,time of first flatus and defecation,time of diet,and amount of activity after surgery.The serum levels of C-reactive protein(CRP),interleukin(IL)-6,IL-10,serum amyloid A protein(SAA),and substance P were measured by the enzyme-linked immunosorbent assay.Then,the spearman correlation coefficient was used to analyze the relationship between the indicators of GI function and inflammation.RESULTS Compared to the placebo-control,improvements in GI function were observed in the MXD groups including reduced incidence of nausea,vomiting,and bloating;and earlier first exhaust time,first defecation time,and feeding time after surgery(P<0.05).On the 1st and 2nd d after surgery,IL-6,CRP and SAA levels in MXD group were lower than that in placebo control,but substance P level was higher,compared to the control(P<0.05).Functional diarrhea occurred in both MXD and XD groups without any other adverse effects,toxic reactions,and allergic reactions.Diarrhea was relieved after the discontinuation of the investigational remedies.Bowel sounds at 12 h after surgery,the occurring time of the first flatus,first defecation,postoperative liquid diet and semiliquid diet were significantly correlated with levels of IL-6,CRP,SAA and substance P on second day after surgery(P<0.05).CONCLUSION Treatment with MXD can relieve inflammatory response and improve GI function after surgery.Moreover,there are significant correlations between them.Furthermore,it does not cause serious adverse reactions.

Advancements in understanding inflammatory responses and the development of cardiovascular diseases under cold stimulation

Cold stimulation has been linked to acute myocardial infarction and other cardiovascular diseases.Residents in the frigid zones,such Heilongjiang Province,experience a higher incidence of adverse cardiovascular events during winter,posing a significant health threat and increasing the overall medical burden.Cold stimulation serves as an detrimental stressor,inducing inflammation in the body.Therefore,understanding the role of inflammatory responses induced by cold stimulation in the occurrence and development of cardiovascular diseases is of paramount importance.Given the impact of cold on inflammation in cardiovascular diseases and the expanding array of anti-inflammatory methods for the treatment of cardiovascular diseases,delving into the inflammatory responses mediated by can significantly complement cardiovascular disease management.This review explorest the synergistic relationship between cold stimulation and inflammation induction,elucidating how this interplay influences the occurrence and progression of cardiovascular diseases.

Progress in the Study of Inflammatory Bowel Disease Patients with Primary Non-Responsiveness

Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.

Silicon dioxide nanoparticles inhibit the effects of cold exposure on metabolism and inflammatory responses in brown adipocytes

Objective:Nanoparticles(NPs)in haze are potentially hazardous to health,which is more severe in the winter.Brown adipose tissue(BAT)plays important roles in obesity,insulin resistance,and diabetes.Though the toxicology of NPs has been intensively studied,few studies have been reported on the antagonistic effects between Silicon dioxide(SiO_(2))NPs and cold exposure in brown adipocytes.Materials and methods:We evaluated changes by quantitative real-time reverse-transcriptase polymerase chain reaction(qRT-PCR)on metabolism genes,plasticity genes and the inflammatory responses genes in brown adipocytes in vitro.Results:The expression of adipogenic genes PRDM16,Dio2,PGC-1αand UCP1 was upregulated upon cold exposure(P<0.05),but downregulated by SiO_(2) NPs(P<0.05).The results demonstrated that there was antagonistic effect between SiO_(2) NPs and cold exposure on the plasticity genes and metabolism genes in brown adipocytes,where the main effects of SiO_(2) NPs or cold exposure on the plasticity genes and metabolism genes were significant(P<0.05).Moreover,the levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-αwere upregulated by SiO_(2) NPs or cold exposure(P<0.05).The factorial analysis indicated that there was also antagonistic effect between SiO_(2) NPs and cold exposure on the toxic effects in brown adipocytes,in which the main effects of cold exposure and/or SiO_(2) NPs on the toxic effects were significant(P<0.05).Conclusion:SiO_(2) NPs inhibit the effect of cold exposure on metabolic genes and inflammatory responses genes in brown adipocytes.

Erroneous presentation of respiratory-hemodynamic disturbances and postsurgical inflammatory responses in patients having undergone abdominal cavity cancer surgery

In this letter to the editor,the authors discuss the findings and shortcomings of a published retrospective study,including 120 patients undergoing surgery for gastric or colon cancer under general anesthesia.The study focused on perioperative dynamic respiratory and hemodynamic disturbances and early postsurgical inflammatory responses.

Influences of dexmedetomidine on stress responses and postoperative cognitive and coagulation functions in patients undergoing radical gastrectomy under general anesthesia

BACKGROUND Radical gastrectomy(RG)is commonly used in the treatment of patients with gastric cancer(GC),but this procedure may lead to stress responses,postoperative cognitive dysfunction,and blood coagulation abnormalities in patients.AIM To investigate the influences of dexmedetomidine(DEX)on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia(GA).METHODS One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed.Of these,50 patients had received conventional anesthesia intervention[control group(CG)]and 52 patients had received DEX in addition to routine anesthesia intervention[observation group(OG)].Inflammatory factor(IFs;tumor necrosis factor-α,TNF-α;interleukin-6,IL-6),stress responses(cortisol,Cor;adrenocorticotropic hormone,ACTH),cognitive function(CF;Mini-Mental State Examination,MMSE),neurological function(neuron-specific enolase,NSE;S100 calciumbinding protein B,S100B),and coagulation function(prothrombin time,PT;thromboxane B2,TXB2;fibrinogen,FIB)were compared between the two groups before surgery(T0),as well as at 6 h(T1)and 24 h(T2)after surgery.RESULTS Compared with T0,TNF-α,IL-6,Cor,ACTH,NSE,S100B,PT,TXB2,and FIB showed a significant increase in both groups at T1 and T2,but with even lower levels in OG vs CG.Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0,but the MMSE score was notably higher in OG compared with CG.CONCLUSION In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA,DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.

Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.

Prognostic value of preoperative prognostic nutritional index and its associations with systemic inflammatory response markers in patients with stage Ⅲ colon cancer

Background: The prognostic nutritional index(PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorectal cancer after tumor resection, the prognostic value remains unknown in patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy. This study aimed to investigate the prognostic value of PNI in patients with stage III colon cancer.Methods: Medical records of 274 consecutive patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December2013 were reviewed. The optimal PNI cutoff value was determined using receiver operating characteristic(ROC) curve analysis. The associations of PNI with systemic inflammatory response markers, including lymphocyte-to-monocyte ratio(LMR), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and C-reactive protein(CRP)level, and clinicopathologic characteristics were assessed using the Chi square or Fisher's exact test. Correlation analysis was performed using Spearman's correlation coefficient. Disease-free survival(DFS) and overall survival(OS)stratified by PNI were analyzed using Kaplan-Meier method and log-rank test, and prognostic factors were identified by Cox regression analyses.Results: The preoperative PNI was positively correlated with LMR(r= 0.483, P < 0.001) and negatively correlated with NLR(r =-0.441, P < 0.001), PLR(r =-0.607, P < 0.001), and CRP level(r =-0.333, P < 0.001). A low PNI(≤49.22)was significantly associated with short OS and DFS in patients with stage ⅢC colon cancer but not in patients with stage ⅢA/ⅢB colon cancer.In addition, patients with a low PNI achieved a longer OS and DFS after being treated with6-8 cycles of adjuvant chemotherapy than did those with < 6 cycles. Multivariate analyses revealed that PNI was independently associated with DFS(hazard ratios 2.001; 95% confidence interval 1.157-3.462; P = 0.013).Conclusion: The present study identified preoperative PNI as a valuable predictor for survival outcomes in patients with stage Ⅲ colon cancer receiving curative tumor resection followed by adjuvant chemotherapy.

In vivo and in vitro protective effect of arginine against intestinal inflammatory response induced by Clostridium perfringens in broiler chickens

Background:Necrotic enteritis is a widespread disease in poultry caused by Clostridium perfringens.We previously reported that dietary arginine supplementation protected the intestinal mucosa of broiler chickens with necrotic enteritis,but the related protective mechanisms remain unclear.The in vivo trial was designed as a 2×2 factorial arrangement to evaluated the effects of arginine supplementation on inflammatory responses,arginine transporters,arginine catabolism and JAK-STAT signalling pathway in broiler chickens challenged with C.perfringens or without C.perfringens.Furthermore,we validated the in vivo results using intestinal epithelial cells of chicken embryos.Results:C.perfringens infection markedly increased gut gross pathological and histopathological lesion scores,promoted liver C.perfringens invasion,reduced serum arginine levels,and elevated jejunal mucosal lysozyme activities(P<0.05),but these effects were significantly reversed by arginine supplementation in vivo(P<0.05).The challenge significantly increased serum procalcitonin levels,jejunal mucosal iNOS activities and jejunal IL-6,TGF-β3,cationic amino acid transporter(CAT)-1,and CAT-3 mRNA expression(P<0.05),whereas arginine supplementation significantly reduced jejunal IFN-γ,IL-1β,IL-6,IL-10,TGF-β3,and CAT-3 mRNA expression(P<0.05).Arginine supplementation significantly attenuated the C.perfringens challenge-induced increases in jejunal i NOS,arginase 2,arginine decarboxylase,arginine:glycine amidinotransferase,JAK1,JAK3,STAT1,and STAT6 mRNA expression(P<0.05).The in vitro experiment showed that C.perfringens challenge markedly increased cellular cytotoxicity and the mRNA expression of IL-1β,IL-8,IL-10,CAT-1 and CAT-3(P<0.05),which were significantly reversed by 50μmol/L and/or400μmol/L arginine pre-treatment(P<0.05).Conclusions:Arginine prevented C.perfringens challenge-induced circulated arginine deficiency,normalized intestinal arginine transport and catabolism,down-regulated JAK-STAT signalling pathway and attenuated the inflammatory response,which exerted protective effects on the intestine of broiler chickens.

Periplaneta americana extract used in patients with systemic inflammatory response syndrome

BACKGROUND:Periplaneta americana extract is recognized to have a positive effect on gastrointestinal mucosa.This study aimed to investigate the effects of periplaneta americana extract on immune function,nutrition status and gastrointestinal complications of early enteral nutrition patients with systemic inflammatory response syndrome(SIRS).METHODS:Patients with SIRS were randomly divided into two groups:treatment and control groups.All patients in the two groups received conventional therapy including enteral nutrition,but periplaneta americana extract,an additional Chinese medicine,was given to the patients in the treatment group.At the beginning of treatment(0 day)and 1,3,and 7 days after treatment,the levels of immunoglobulin(Ig A),total lymphocyte count(TLC),total protein(TP)and prealbumin(PA)were respectively tested in patients'venous blood.The incidences of bloating,diarrhea,aspiration pneumonia and high blood sugar at 7 days after treatment were recorded.The mortality of the patients in 28 days was recorded.RESULTS:At 3 and 7 days after treatment,the levels of Ig A and TLC in the treatment group were higher than those in the control group(P<0.05).At 7 days after treatment,the levels of TP and PA in the treatment group were higher than those in the control group(P<0.05).The incidences of bloating and diarrhea in the treatment group were lower than those in the control group,the differences were significant(P<0.05).The mortality of treatment group was lower than that of the control group(P>0.05).CONCLUSION:Periplaneta americana extract could reduce gastrointestinal complications and improve immune function and nutritional status in patients with systemic inflammatory response syndrome.

Impact of sugar beet pulp and wheat bran on serum biochemical profile,inflammatory responses and gut microbiota in sows during late gestation and lactation

Background:Sows are frequently subjected to various stresses during late gestation and lactation,which trigger inflammatory response and metabolic disorders.Dietary fiber can influence animal health by modulating gut microbiota and their by-products,with the effects depending upon the source of the dietary fiber.This study aimed to evaluate the impacts of different fiber sources on body condition,serum biochemical parameters,inflammatory responses and fecal microbiota in sows from late gestation to lactation.Methods:Forty-five multiparous sows(Yorkshire×Landrace;3–6 parity)were assigned to 1 of 3 dietary treatments from d 85 of gestation to the end of lactation(d 21 post-farrowing):a control diet(CON,a corn-soybean meal diet),a sugar beet pulp diet(SBP,20%SBP during gestation and 10%SBP during lactation),and a wheat bran diet(WB,30%WB during gestation and 15%WB during lactation).Results:Compared with CON,supplementation of SBP decreased(P<0.05)lactation BW loss,reduced(P<0.05)serum concentration of total cholesterol,non-esterified fatty acids,interleukin-6 and tumor necrosis factor-α,and increased(P<0.05)fecal water content on d 110 of gestation and d 21 of lactation,while supplementation of WB reduced(P<0.05)serum concentration of total cholesterol on d 110 of gestation,increased(P<0.05)fecal water content and decreased(P<0.05)serum interleukin-6 concentration on d 110 of gestation and d 21 of lactation.In addition,sows fed SBP had lower(P<0.01)abundance of Clostridium_sensu_stricto_1 and Terrisporobacter than those fed CON,but had greater(P<0.05)abundance of Christensenellaceae_R-7_group and Ruminococcaceae_UCG-002 than those fed the other two diets on d 110 of gestation.On d 21 of lactation,supplementation of SBP decreased(P<0.05)the abundance of Firmicutes and Lactobacillus,but enriched(P<0.05)the abundance of Christensenellaceae_R-7_group,Prevotellaceae_NK3B31_group,Ruminococcaceae_UCG-002,Prevotellaceae_UCG_001 and unclassified_f__Lachnospiraceae compared with WB.Compared with CON,sows fed SBP had greater(P<0.05)fecal concentrations of acetate,butyrate and total SCFAs during gestation and lactation,while sows fed WB only had greater(P<0.05)fecal concentration of butyrate during lactation.Conclusions:Supplementation of dietary fiber during late gestation and lactation could improve sow metabolism and gut health,and SBP was more effective than WB.

Expression and Significance of Toll-like Receptor 2,4 of Peripheral Blood Mononuclear Cells in Acute Abdomen Patients Associated with Systemic Inflammatory Response Syndrome

The changes of Toll-like receptor （TLR） 2, 4 of peripheral blood mononuclear cells （PBMCs） in the acute abdomen patients associated with systemic inflammatory response syndrome （SIRS） and their potential significance were explored. A clinical study was performed on 103 acute abdomen patients in whom 65 were associated with SIRS. Forty healthy individuals served as normal controls. The mRNA expression of TLR2, 4 was detected by RT-PCR, and the expression of TNF-α and IL-6 by ELISA. The level of plasma endotoxin, hospital stay and mortality were measured. It was found that the endotoxin level was increased to varying degrees in all the acute abdomen patients, and the endotoxin level was and hospital stay longer in SIRS group than in non-SIRS group （P〈0.01）. TLR2 mRNA, TLR4 mRNA, IL-6 and TNF-ct could be detected with low value in normal controls, but they were up-regulated markedly on the 1 st day after admission. Then TLR4 mRNA, IL-6 and TNF-α were decreased gradually, but TLR2 mRNA maintained at a high level till the 5th day. These indexes above in SIRS group were higher than those in non-SIRS group （P〈0.01）. The results of correlation analysis revealed the expression of TLR2, 4 mRNA was positively correlated with the levels of TNF-α and IL-6, and the hospital stay, The results of Logistic regression demonstrated that overexpression of TLR2, 4 mRNA might result in higher risk of multiple organ dysfunction syndrome （MODS）. It was concluded that in the acute abdomen patients associated with SIRS, the expression of TLR2, 4 in PBMCs was increased markedly, suggesting that TLR might play an important role in the pathogenesis of acute abdomen associated with SIRS.

Effects of internal iliac artery embolization on systemic inflammatory response syndrome in dogs with simulatedpelvic-fracture combined with massive bleeding

Background: Pelvic fracture combined with massive bleeding(PFCMB) is a complex issue in clinical practice. Currently, the use of angiography and embolization for the treatment of PFCMB obtains good results. The aim of this study is to observe the effects of early internal iliac artery embolization on the systemic inflammatory response syndrome(SIRS) in dogs with simulated-pelvic-fracture combined with massive bleeding.Methods: Twenty adult dogs were randomly divided into an embolization group(EG) and a control group(CG). For the two groups, heart rate, respiratory rate and body temperature and other physiological variables were measured, and IL-6, TNF-α and arterial blood gas levels were monitored. These variables were assayed every 30 min until death in the CG, while dogs in the EG underwent arterial angiography after 60 min of modeling. The internal iliac artery was embolized on the injured side.Results: The average time to SIRS in the CG was 3.56 h, occurring at a rate of 90%(9/10) within 24 h, with a mortality rate of 50%(5/10); the average time to SIRS for the EG was 5.33 h, occurring at a rate of 30%(3/10) within 24 h, with a mortality rate of 10%(1/10). When SIRS occurred in the EG, the mean plasma IL-6 level was 52.66±7.38pg/ml and the TNF-ps, tα level was 11.45±2.72ng/ml, showing a significant difference with those of the CG(P<0.05). In the two grouhe respiratory rate and leukocyte levels were higher at each monitored time after modeling than those before modeling; the mean arterial pressure, levels of hemoglobin and oxygen partial pressure were significantly lower at each time point after modeling than those before modeling except for the mean arterial pressure at 0h in EG; the platelet levels at 4 and 8h were higher than those before modeling; and the differences were statistically significant(P<0.05). In the EG, the mean arterial pressure, heart rate, respiratory rate and hemoglobin levels at 2, 4 and 8h were lower than those at 0h; the levels of leukocytes, platelets and carbon dioxide partial pressure at 4 and 8h after modeling were higher than those at 0h, and the differences were statistically significant(P<0.05, P<0.01); in the CG after modeling, the mean arterial pressure, levels of hemoglobin and carbon dioxide partial pressure at 2, 4 and 8h were lower than those at 0h; the levels of heart rate and leukocytes were higher than those before modeling; the respiratory rate and platelet levels at 4 and 8h were higher than those at 0h; and the differences were statistically significant(P<0.05). The levels of the mean arterial pressure and hemoglobin at 4 and 8h and the p H values at 8h after modeling in the EG were significantly higher than those in the CG, while the heart rate and respiratory rate at 4 and 8h were significantly lower than those in the CG. The p H values at 8h after modeling were significantly lower than those of the other monitored times in the CG(P<0.05, P<0.01). The two groups had elevated levels of alkaline phosphatase after injury induction.Conclusion: Through the use of an on-spot interventional treatment cabin, early internal iliac artery embolization can control bleeding associated with pelvic fractures, delay the occurrence of SIRS, and improve the success rate of the treatment of pelvic fracture combined with bleeding.

Comparison of clinical efficacy and postoperative inflammatory response between laparoscopic and open radical resection of colorectal cancer

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has increased annually,which has seriously threatened the health and quality of life of patients.In the treatment of CRC,both laparoscopic and radical resection are widely used.AIM To explore and discuss clinical efficacy and postoperative inflammatory response of laparoscopic and open radical resection of CRC.METHODS A total of 96 patients with CRC diagnosed in our hospital from March 2016 to April 2021 were selected,and were divided into the study group(n=48)and control group(n=48)using a simple random method.The control group was treated with open radical resection of CRC,and the study group was treated with laparoscopic radical resection of CRC.The perioperative conditions(operation time,intraoperative blood loss,the recovery time of gastrointestinal function,number of lymph node dissections and length of hospital stay),inflammatory response index levels[interleukin(IL)-6,IL-8,IL-10,C-reactive protein(CRP)]before and after operation,pain stress response indices[levels of neuropeptide(NPY),prostaglandin E2(PGE2),5-hydroxytryptamine(5-HT)],and the incidence of the complications between the two groups were counted.RESULTS The operation time in the study group was(186.18±33.54 min),which was longer than that of the control group(129.38±26.83 min),but the intraoperative blood loss(111.34±21.45 mL),recovery time of gastrointestinal function(25.35±4.55 h),and hospital stay(10.09±2.38 d)were better than those in the control group(163.77±32.41 mL,36.06±7.13 h,13.51±3.66 d)(P<0.05).There was no significant difference in the number of lymph node dissections between the study group(15.19±3.04)and the control group(16.20±2.98)(P>0.05).There was no significant difference between the levels of serum IL-6(9.79±4.11 ng/mL),IL-8(3.79±1.71 ng/L),IL-10(48.96±12.51 ng/L)and CRP(7.98±2.33 mg/L)in the study group and the control group(10.56±3.78 ng/mL,4.08±1.45 ng/L,50.13±11.67 ng/L,8.29±2.60 mg/L)before the operation(P>0.05).After the operation,there was no significant difference between the levels of serum IL-6(19.11±6.68 ng/mL).There was no significant difference in serum NPY(109.79±13.46 UG/L),PGE2(269.54±37.34 ng/L),5-HT(151.70±18.86 ng/L)between the study group and the control group(113.29±15.01 UG/L,273.91±40.04 ng/L,148.85±20.45 ng/L)before the operation(P>0.05).The incidence of the complications in the study group(4.17%)was lower than that of the control group(18.75%)(P<0.05).CONCLUSION Laparoscopic radical resection of CRC can reduce surgical trauma,inflammatory response and pain stress caused by surgery,which shortens rehabilitation of patients,with a low incidence of complications.

LncRNA Airsci increases the inflammatory response after spinal cord injury in rats through the nuclear factor kappa B signaling pathway

Spinal cord injury(SCI)is a serious traumatic event to the central nervous system.Studies show that long non-coding RNAs(lncRNAs)play an important role in regulating the inflammatory response in the acute stage of SCI.Here,we investigated a new lncRNA related to spinal cord injury and acute inflammation.We analyzed the expression profile of lncRNAs after SCI,and explored the role of lncRNA Airsci(acute inflammatory response in SCI)on recovery following acute SCI.The rats were divided into the control group,SCI group,and SCI+lncRNA Airsci-siRNA group.The expression of inflammatory factors,including nuclear factor kappa B[NF-κB(p65)],NF-κB inhibitor IκBαand phosphorylated IκBα(p-IκBα),and the p-IκBα/IκBαratio were examined 1–28 days after SCI in rats by western blot assay.The differential lncRNA expression profile after SCI was assessed by RNA sequencing.The differentially expressed lncRNAs were analyzed by bioinformatics technology.The differentially expressed lncRNA Airsci,which is involved in NF-κB signaling and associated with the acute inflammatory response,was verified by quantitative real-time PCR.Interleukin(IL-1β),IL-6 and tumor necrosis factor(TNF-α)at 3 days after SCI were measured by western blot assay and quantitative real-time PCR.The histopathology of the spinal cord was evaluated by hematoxylin-eosin and Nissl staining.Motor function was assessed with the Basso,Beattie and Bresnahan Locomotor Rating Scale.Numerous differentially expressed lncRNAs were detected after SCI,including 151 that were upregulated and 186 that were downregulated in the SCI 3 d group compared with the control group.LncRNA Airsci was the most significantly expressed among the five lncRNAs involved in the NF-κB signaling pathway.LncRNA Airsci-siRNA reduced the inflammatory response by inhibiting the NF-κB signaling pathway,alleviated spinal cord tissue injury,and promoted the recovery of motor function in SCI rats.These findings show that numerous lncRNAs are differentially expressed following SCI,and that inhibiting lncRNA Airsci reduces the inflammatory response through the NF-κB signaling pathway,thereby promoting functional recovery.All experimental procedures and protocols were approved by the approved by the Animal Ethics Committee of Jining Medical University(approval No.JNMC-2020-DW-RM-003)on January 18,2020.