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.

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.

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.

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.

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.

Effect of glutarnate on inflammatory responses of intestine and brain after focal cerebral ischemia

AIM: To study the modulation of glutamate on post-ischemic intestinal and cerebral inflammatory responses in a ischemic and excitotoxic rat model.METHODS: Adult male rats were subjected to bilateral carotid artery occlusion for 15 min and injection of monosodium glutamate intraperitoneally, to decapitate them at selected time points. Tumor necrosis factor alpha (TNF-α) level and nuclear factor kappa B (NF-κB) activity were determined by enzyme-linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA), respectively.Hemodynamic parameters were monitored continuously during the whole process of cerebral ischemia and reperfusion.RESULTS: Monosodium glutamate (MSG) treated rats displayed statistically significant high levels of TNF-α in cerebral and intestinal tissuess within the first 6 h of ischemia. The rats with cerebral ischemia showed a minor decrease of TNF-α production in cerebral and intestinal tissuess. The rats with cerebral ischemia and treated with MSG displayed statistically significant low levels of TNF-α in cerebral and intestinal tissues. These results correlated significantly with NF-κB production calculated at the same intervals. During experiment, the mean blood pressure and heart rates in all groups were stable.CONCLUSION: Glutamate is involved in the mechanism of intestinal and cerebral inflammation responses. The effects of glutamate on cerebral and intestinal inflammatory responses after ischemia are up-regulated at the transcriptional level,through the NF-κB signal transduction pathway.

Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and Inflammatory Responses in Rats with PM2.5 Induced Lung Injuries

Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.

Regulatory role of microRNA on inflammatory responses of diabetic retinopathy

The prevalence of diabetes has been increasing in the U.S., with diabetes as a significant concern for patients＇ physical and financial health. Diabetic retinopathy is the leading cause of vi- sual loss in working-age of adults and is characterized by retinal neurodegeneration and microvascular abnormalities in the eye. Hyperglycemia is one significant risk factor for diabetic retinop- athy and can result in increased inflammatory responses and vascular dysfunction. However, the molecular mechanisms un-derlying these pathologies are not fully understood. Although treatments are currently available for the patients with prolif-erative diabetic retinopathy or macular edema, including laser photocoagulation, steroids, or anti-vascular endothelial growth factor （VEGF） injections, many patients fail to respond to these therapies. Therefore, it is imperative to develop additional novel therapeutics for diabetic retinopathy.

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.

Bacillus licheniformis PF9 improves barrier function and alleviates inflammatory responses against enterotoxigenic Escherichia coli F4 infection in the porcine intestinal epithelial cells

Background:Enterotoxigenic Escherichia coli(ETEC)F4 commonly colonizes the small intestine and releases enterotoxins that impair the intestinal barrier function and trigger inflammatory responses.Although Bacillus licheniformis(B.licheniformis)has been reported to enhance intestinal health,it remains to be seen whether there is a functional role of B.licheniformis in intestinal inflammatory response in intestinal porcine epithelial cell line(IPEC-J2)when stimulated with ETEC F4.Methods:In the present study,the effects of B.licheniformis PF9 on the release of pro-inflammation cytokines,cell integrity and nuclear factor-κB(NF-κB)activation were evaluated in ETEC F4-induced IPEC-J2 cells.Results:B.licheniformis PF9 treatment was capable of remarkably attenuating the expression levels of inflammation cytokines tumor necrosis factor-α(TNF-α),interleukin(IL)-8,and IL-6 during ETEC F4 infection.Furthermore,the gene expression of Toll-like receptor 4(TLR4)-mediated upstream related genes of NF-κB signaling pathway has been significantly inhibited.These changes were accompanied by significantly decreased phosphorylation of p65 NF-κB during ETEC F4 infection with B.licheniformis PF9 treatment.The immunofluorescence and western blotting analysis revealed that B.licheniformis PF9 increased the expression levels of zona occludens 1(ZO-1)and occludin(OCLN)in ETEC F4-infected IPEC-J2 cells.Meanwhile,the B.licheniformis PF9 could alleviate the injury of epithelial barrier function assessed by the trans-epithelial electrical resistance(TEER)and cell permeability assay.Interestingly,B.licheniformis PF9 protect IPEC-J2 cells against ETEC F4 infection by decreasing the gene expressions of virulence-related factors(including luxS,estA,estB,and elt)in ETEC F4.Conclusions:Collectively,our results suggest that B.licheniformis PF9 might reduce inflammation-related cytokines through blocking the NF-κB signaling pathways.Besides,B.licheniformis PF9 displayed a significant role in the enhancement of IPEC-J2 cell integrity.

Expression patterns and action analysis of genes associated with inflammatory responses during rat liver regeneration

AIM： To study the relationship between inflammatory response and liver regeneration （LR） at transcriptional level.METHODS： After partial hepatectomy （PH） of rats, the genes associated with inflammatory response were obtained according to the databases, and the gene expression changes during LR were checked by the Rat Genome 230 2.0 army. RESULTS： Two hundred and thirty-nine genes were associated with liver regeneration. The initial and total expressing gene numbers found in initiation phase （0.5-4 h after PH）, G0/G1 transition （4-6 h after PH）, cell proliferation （6-66 h after PH）, cell differentiation and structure-function reconstruction （66-168 h after PH） of liver regeneration were 107, 34, 126, 6 and 107, 92, 233, 145 respectively, showing that the associated genes were mainly triggered at the beginning of liver regeneration, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups： only up-regulated, predominantly up-, only down-, predominantly down-, up- and down-, involving 92, 25, 77, 14 and 31 genes, respectively. The total times of their up- and down-regulated expression were 975 and 494, respectively, demonstrating that the expressions of the majority of genes were increased, and that of a few genes were decreased. Their time relevance was classified into 13 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 33 types, suggesting that the activities were diverse and complex during liver regeneration. CONCLUSION： Inflammatory response is closelyassociated with liver regeneration, in which 239 LR- associated genes play an important role.

Molecular mechanisms and roles of inflammatory responses on low-frequency residual hearing after cochlear implantation

Preservation of low-frequency residual hearing is very important for combined electro-acoustic stimulation after cochlear implantation.However,in clinical practice,loss of low-frequency residual hearing often occurs after cochlear implantation and its mechanisms remain unclear.Factors affecting lowfrequency residual hearing after cochlear implantation are one of the hot spots in current research.Inflammation induced by injury associated with cochlear implantation is deemed to be significant,as it may give rise to low-frequency residual hearing loss by interfering with the blood labyrinth barrier and neural synapses.Pathological changes along the pathway for low-frequency auditory signals transmission may include latent factors such as damage to neuroepithelial structures,synapses,stria vascularis and other ultrastructures.In this review,current research on mechanisms of low-frequency residual hearing loss after cochlear implantation and possible roles of inflammatory responses are summarized.

Inflammatory responses to Hydroxyapatite implants in middle ear in rats

Objective To study local inflammatory response after implantation of hydroxyapatite synthetic ossicular prosthesis. Methods Hydroxyapatite granules were implanted in the bulla in 32 rats. Sham surgical procedures were performed in 10 rats as the control. Animals were sacrificed at 1 to 300 days after surgery. Bulla sections, stained with HE and Mallory’s azan, were examined for numbers and percentages of various inflammatory cell types. Results Slightly more inflammatory reaction was seen in animals with the implant than in the controls, mostly during the early stage following the implantation procedure. Few inflammatory cells were observed at later times. There were satisfactory fibrosis in both implanted and control ears. Conclusion The results indicate that hydroxyapatite synthetic prosthesis is a biocompatible implantation material in the middle ear. Nonetheless, the presence of inflammatory reaction immediately following implantation implies that control of infection is important in the early times after the implantation procedure.

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory effects.In this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus macaques.We found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP.Therefore,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP.

Nanotopographic micro-nano forces finely tune the conformation of macrophage mechanosensitive membrane protein integrinβ_(2)to manipulate inflammatory responses

Finely tuning mechanosensitive membrane proteins holds great potential in precisely controlling inflammatory responses.In addition to macroscopic force,mechanosensitive membrane proteins are reported to be sensitive to micro-nano forces.Integrinβ_(2),for example,might undergo a piconewton scale stretching force in the activation state.High-aspect-ratio nanotopographic structures were found to generate nN-scale biomechanical force.Together with the advantages of uniform and precisely tunable structural parameters,it is fascinating to develop low-aspect-ratio nanotopographic structures to generate micro-nano forces for finely modulating their conformations and the subsequent mechanoimmiune responses.In this study,low-aspect-ratio nanotopographic structures were developed to finely manipulate the conformation of integrinβ_(2).The direct interaction of forces and the model molecule integrinαXβ_(2)was first performed.It was demonstrated that pressing force could successfully induce conformational compression and deactivation of integrinαXβ_(2),and approximately 270 to 720 pN may be required to inhibit its conformational extension and activation.Three low-aspect-ratio nanotopographic surfaces(nanohemispheres,nanorods,and nanoholes)with various structural parameters were specially designed to generate the micro-nano forces.It was found that the nanorods and nanohemispheres surfaces induce greater contact pressure at the contact interface between macrophages and nanotopographic structures,particularly after cell adhesion.These higher contact pressures successfully inhibited the conformational extension and activation of integrinβ_(2),suppressing focal adhesion activity and the downstream PI3K-Akt signaling pathway,reducing NF-κB signaling and macrophage inflammatory responses.Our findings suggest that nanotopographic structures can be used to finely tune mechanosensitive membrane protein conformation changes,providing an effective strategy for precisely modulating inflammatory responses.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

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.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy

BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma(dCCA)who underwent pancreat-oduodenectomy(PD).METHODS This single-center study included 216 patients with dCCA after PD between January 1,2011,and December 31,2022.The individuals were categorized into two sets based on their systemic inflammatory response index(SIRI)levels:A low SIRI group(SIRI<1.5,n=123)and a high SIRI group(SIRI≥1.5,n=93).Inflam-matory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves.Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival(OS)and recurrence-free survival(RFS).RESULTS The study included a total of 216 patients,with 58.3%being male and a mean age of 65.6±9.6 years.123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA.SIRI had an area under the curve value of 0.674 for diagnosing dCCA,showing better performance than other inflammatory biomarkers.Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD,leading to lower OS[hazard ratios(HR)=1.868,P=0.006]and RFS(HR=0.949,P<0.001).Additionally,survival analysis indicated a significantly better prognosis for patients in the low SIRI group(P<0.001).CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

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.