BACKGROUND Surgical care of the hand plays a crucial role in the medical field,as problems with the hand can profoundly affect a patient's quality of life and function.In order to meet the needs of patients,improv...BACKGROUND Surgical care of the hand plays a crucial role in the medical field,as problems with the hand can profoundly affect a patient's quality of life and function.In order to meet the needs of patients,improve patient satisfaction and improve treatment outcomes,high-quality service models have been introduced in the field of nursing.AIM To explore the effect analysis of applying high-quality service model to surgical nursing.METHODS We conducted a retrospective study of patients who underwent hand surgery at our hospital between 2019 and 2022,using a quality service model that included improved patient education,pain management,care team collaboration,and effective communication.Another group of patients received traditional care as a control group.We compared postoperative recovery,satisfaction,complication rate,and length of hospital stay between the two groups.Inferential statistics were used to compare the difference between the two groups by independent sample t test,Chi-square test and other methods to evaluate the effect of intervention measures.RESULTS Postoperative recovery time decreased from 17.8±2.3 d to 14.5±2.1 d,pain score decreased from 4.7±1.9 to 3.2±1.4,and hand function score increased from 78.4±7.1 to 88.5±6.2.In terms of patient satisfaction,the quality service model group scored 87.3±5.6 points,which was significantly higher than that of the traditional care group(74.6±6.3 points).At the same time,patients'understanding of medical information also improved from 6.9±1.4 to 8.6±1.2.In terms of postoperative complications,the application of the quality service model reduced the incidence of postoperative complications from 26%to 10%,the incidence of infection from 12%to 5%,and the incidence of bleeding from 10%to 3%.The reduction in these data indicates that the quality service model plays a positive role in reducing the risk of complications.In addition,the average hospital stay of patients in the quality service model group was shortened from 6.8±1.5 d to 5.2±1.3 d,and the hospitalization cost was also reduced from 2800±600 yuan to 2500±500 yuan.CONCLUSION Applying a quality service model to hand surgery care can significantly improve patient clinical outcomes,including faster recovery,less pain,greater satisfaction,and reduced complication rates.展开更多
Chronic pancreatitis affects many individuals around the world,and the study of the underlying mechanisms leading to better treatment possibilities are important tasks.Therefore,animal models are needed to illustrate ...Chronic pancreatitis affects many individuals around the world,and the study of the underlying mechanisms leading to better treatment possibilities are important tasks.Therefore,animal models are needed to illustrate the basic study of pancreatitis.Recently,animal models of acute and chronic pancreatitis have been thoroughly reviewed,but few reviews address the important aspect on the translation of animal studies to human studies.It is well known that pancreatitis is associated with epigastric pain,but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear.Using animal models to study pancreatitis associated visceral pain is difficult,however,these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain.In this review,the animal models of acute,chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.展开更多
BACKGROUND Transarterial chemoembolization(TACE)is the first-line treatment for patients with unresectable liver cancer;however,TACE is associated with postembolization pain.AIM To analyze the risk factors for acute a...BACKGROUND Transarterial chemoembolization(TACE)is the first-line treatment for patients with unresectable liver cancer;however,TACE is associated with postembolization pain.AIM To analyze the risk factors for acute abdominal pain after TACE and establish a predictive model for postembolization pain.METHODS From January 2018 to September 2018,all patients with liver cancer who underwent TACE at our hospital were included.General characteristics;clinical,imaging,and procedural data;and postembolization pain were analyzed.Postembolization pain was defined as acute moderate-to-severe abdominal pain within 24 h after TACE.Logistic regression and a classification and regression tree were used to develop a predictive model.Receiver operating characteristic curve analysis was used to examine the efficacy of the predictive model.RESULTS We analyzed 522 patients who underwent a total of 582 TACE procedures.Ninety-seven(16.70%)episodes of severe pain occurred.A predictive model built based on the dataset from classification and regression tree analysis identified known invasion of blood vessels as the strongest predictor of subsequent performance,followed by history of TACE,method of TACE,and history of abdominal pain after TACE.The area under the receiver operating characteristic curve was 0.736[95%confidence interval(CI):0.682-0.789],the sensitivity was 73.2%,the specificity was 65.6%,and the negative predictive value was 92.4%.Logistic regression produced similar results by identifying age[odds ratio(OR)=0.971;95%CI:0.951-0.992;P=0.007),history of TACE(OR=0.378;95%CI:0.189-0.757;P=0.007),history of abdominal pain after TACE(OR=6.288;95%CI:2.963-13.342;P<0.001),tumor size(OR=1.978;95%CI:1.175-3.330;P=0.01),multiple tumors(OR=2.164;95%CI:1.243-3.769;P=0.006),invasion of blood vessels(OR=1.756;95%CI:1.045-2.950;P=0.034),and TACE with drug-eluting beads(DEBTACE)(OR=2.05;95%CI:1.260-3.334;P=0.004)as independent predictive factors for postembolization pain.CONCLUSION Blood vessel invasion,TACE history,TACE with drug-eluting beads,and history of abdominal pain after TACE are predictors of acute moderate-to-severe pain.The predictive model may help medical staff to manage pain.展开更多
Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Acute pain,provoked generally after the activation of peripheral nociceptors,is an adaptive sensory function that alerts the individual to avoid noxious stimuli.However,uncontrolled acute pain has a maladaptive role i...Acute pain,provoked generally after the activation of peripheral nociceptors,is an adaptive sensory function that alerts the individual to avoid noxious stimuli.However,uncontrolled acute pain has a maladaptive role in sensory activity leading to development of a chronic pain state which persists even after the damage is resolved,or in some cases,in the absence of an initial local acute injury.Huge numbers of people suffer from visceral pain at least once during their life span,leading to substantial health care costs.Although studies reporting on the mechanism of visceral pain are accumulating,it is still not precisely understood.Therefore,this review aims to elucidate the mechanism of visceral pain through an evaluation of different animal models and their application to develop novel therapeutic approaches for treating visceral pain.To assess the nociceptive responses in viscera,several visceral pain models such as inflammatory,traction,stress and genetic models utilizing different methods of measurement have been devised.Among them,the inflammatory and traction models are widely used for studying the visceral pain mechanism of different disease conditions and post-operative surgery in humans and animals.A hapten,2,4,6-trinitrobenzene sulfonic acid(TNBS),has been extensively used as an inflammatory agent to induce visceral pain.The traction model seems to cause a strong pain stimulation and autonomic reaction and could thus be the most appropriate model for studying the underlying visceral pain mechanism and for probing the therapeutic efficacies of various anesthetic and analgesics for the treatment of visceral pain and hyperalgesia.展开更多
Purpose: To formulate and demonstrate methods for regression modeling of probabilities and dispersions for individual-patient longitudinal outcomes taking on discrete numeric values. Methods: Three alternatives for mo...Purpose: To formulate and demonstrate methods for regression modeling of probabilities and dispersions for individual-patient longitudinal outcomes taking on discrete numeric values. Methods: Three alternatives for modeling of outcome probabilities are considered. Multinomial probabilities are based on different intercepts and slopes for probabilities of different outcome values. Ordinal probabilities are based on different intercepts and the same slope for probabilities of different outcome values. Censored Poisson probabilities are based on the same intercept and slope for probabilities of different outcome values. Parameters are estimated with extended linear mixed modeling maximizing a likelihood-like function based on the multivariate normal density that accounts for within-patient correlation. Formulas are provided for gradient vectors and Hessian matrices for estimating model parameters. The likelihood-like function is also used to compute cross-validation scores for alternative models and to control an adaptive modeling process for identifying possibly nonlinear functional relationships in predictors for probabilities and dispersions. Example analyses are provided of daily pain ratings for a cancer patient over a period of 97 days. Results: The censored Poisson approach is preferable for modeling these data, and presumably other data sets of this kind, because it generates a competitive model with fewer parameters in less time than the other two approaches. The generated probabilities for this model are distinctly nonlinear in time while the dispersions are distinctly nonconstant over time, demonstrating the need for adaptive modeling of such data. The analyses also address the dependence of these daily pain ratings on time and the daily numbers of pain flares. Probabilities and dispersions change differently over time for different numbers of pain flares. Conclusions: Adaptive modeling of daily pain ratings for individual cancer patients is an effective way to identify nonlinear relationships in time as well as in other predictors such as the number of pain flares.展开更多
Software development is an important part of computer technology.only by ensuring the applicability and efficiency of the software can it really improve the efficiency of production and life,and truly inject new power...Software development is an important part of computer technology.only by ensuring the applicability and efficiency of the software can it really improve the efficiency of production and life,and truly inject new power into the economic benefits of the industry.As the theoretical basis of software development,the software development model directly determines the quality of software development.In this paper,starting with information technology as an important tool to improve modern management,it brings out the difficulties and pain points in the analysis of software development needs,and first puts forward the software development innovation model for building a composite core users.It takes core users with compound qualities and capabilities as the main line and guides the entire development process to enable both parties to communicate accurately and solve the pain points of demand communication,function optimization and project control to the greatest extent.Exploring application innovation in the software development model can promote innovation in the software industry.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic ...BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.展开更多
文摘BACKGROUND Surgical care of the hand plays a crucial role in the medical field,as problems with the hand can profoundly affect a patient's quality of life and function.In order to meet the needs of patients,improve patient satisfaction and improve treatment outcomes,high-quality service models have been introduced in the field of nursing.AIM To explore the effect analysis of applying high-quality service model to surgical nursing.METHODS We conducted a retrospective study of patients who underwent hand surgery at our hospital between 2019 and 2022,using a quality service model that included improved patient education,pain management,care team collaboration,and effective communication.Another group of patients received traditional care as a control group.We compared postoperative recovery,satisfaction,complication rate,and length of hospital stay between the two groups.Inferential statistics were used to compare the difference between the two groups by independent sample t test,Chi-square test and other methods to evaluate the effect of intervention measures.RESULTS Postoperative recovery time decreased from 17.8±2.3 d to 14.5±2.1 d,pain score decreased from 4.7±1.9 to 3.2±1.4,and hand function score increased from 78.4±7.1 to 88.5±6.2.In terms of patient satisfaction,the quality service model group scored 87.3±5.6 points,which was significantly higher than that of the traditional care group(74.6±6.3 points).At the same time,patients'understanding of medical information also improved from 6.9±1.4 to 8.6±1.2.In terms of postoperative complications,the application of the quality service model reduced the incidence of postoperative complications from 26%to 10%,the incidence of infection from 12%to 5%,and the incidence of bleeding from 10%to 3%.The reduction in these data indicates that the quality service model plays a positive role in reducing the risk of complications.In addition,the average hospital stay of patients in the quality service model group was shortened from 6.8±1.5 d to 5.2±1.3 d,and the hospitalization cost was also reduced from 2800±600 yuan to 2500±500 yuan.CONCLUSION Applying a quality service model to hand surgery care can significantly improve patient clinical outcomes,including faster recovery,less pain,greater satisfaction,and reduced complication rates.
文摘Chronic pancreatitis affects many individuals around the world,and the study of the underlying mechanisms leading to better treatment possibilities are important tasks.Therefore,animal models are needed to illustrate the basic study of pancreatitis.Recently,animal models of acute and chronic pancreatitis have been thoroughly reviewed,but few reviews address the important aspect on the translation of animal studies to human studies.It is well known that pancreatitis is associated with epigastric pain,but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear.Using animal models to study pancreatitis associated visceral pain is difficult,however,these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain.In this review,the animal models of acute,chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.
基金Supported by Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,China,No.2020372769.
文摘BACKGROUND Transarterial chemoembolization(TACE)is the first-line treatment for patients with unresectable liver cancer;however,TACE is associated with postembolization pain.AIM To analyze the risk factors for acute abdominal pain after TACE and establish a predictive model for postembolization pain.METHODS From January 2018 to September 2018,all patients with liver cancer who underwent TACE at our hospital were included.General characteristics;clinical,imaging,and procedural data;and postembolization pain were analyzed.Postembolization pain was defined as acute moderate-to-severe abdominal pain within 24 h after TACE.Logistic regression and a classification and regression tree were used to develop a predictive model.Receiver operating characteristic curve analysis was used to examine the efficacy of the predictive model.RESULTS We analyzed 522 patients who underwent a total of 582 TACE procedures.Ninety-seven(16.70%)episodes of severe pain occurred.A predictive model built based on the dataset from classification and regression tree analysis identified known invasion of blood vessels as the strongest predictor of subsequent performance,followed by history of TACE,method of TACE,and history of abdominal pain after TACE.The area under the receiver operating characteristic curve was 0.736[95%confidence interval(CI):0.682-0.789],the sensitivity was 73.2%,the specificity was 65.6%,and the negative predictive value was 92.4%.Logistic regression produced similar results by identifying age[odds ratio(OR)=0.971;95%CI:0.951-0.992;P=0.007),history of TACE(OR=0.378;95%CI:0.189-0.757;P=0.007),history of abdominal pain after TACE(OR=6.288;95%CI:2.963-13.342;P<0.001),tumor size(OR=1.978;95%CI:1.175-3.330;P=0.01),multiple tumors(OR=2.164;95%CI:1.243-3.769;P=0.006),invasion of blood vessels(OR=1.756;95%CI:1.045-2.950;P=0.034),and TACE with drug-eluting beads(DEBTACE)(OR=2.05;95%CI:1.260-3.334;P=0.004)as independent predictive factors for postembolization pain.CONCLUSION Blood vessel invasion,TACE history,TACE with drug-eluting beads,and history of abdominal pain after TACE are predictors of acute moderate-to-severe pain.The predictive model may help medical staff to manage pain.
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
文摘Acute pain,provoked generally after the activation of peripheral nociceptors,is an adaptive sensory function that alerts the individual to avoid noxious stimuli.However,uncontrolled acute pain has a maladaptive role in sensory activity leading to development of a chronic pain state which persists even after the damage is resolved,or in some cases,in the absence of an initial local acute injury.Huge numbers of people suffer from visceral pain at least once during their life span,leading to substantial health care costs.Although studies reporting on the mechanism of visceral pain are accumulating,it is still not precisely understood.Therefore,this review aims to elucidate the mechanism of visceral pain through an evaluation of different animal models and their application to develop novel therapeutic approaches for treating visceral pain.To assess the nociceptive responses in viscera,several visceral pain models such as inflammatory,traction,stress and genetic models utilizing different methods of measurement have been devised.Among them,the inflammatory and traction models are widely used for studying the visceral pain mechanism of different disease conditions and post-operative surgery in humans and animals.A hapten,2,4,6-trinitrobenzene sulfonic acid(TNBS),has been extensively used as an inflammatory agent to induce visceral pain.The traction model seems to cause a strong pain stimulation and autonomic reaction and could thus be the most appropriate model for studying the underlying visceral pain mechanism and for probing the therapeutic efficacies of various anesthetic and analgesics for the treatment of visceral pain and hyperalgesia.
文摘Purpose: To formulate and demonstrate methods for regression modeling of probabilities and dispersions for individual-patient longitudinal outcomes taking on discrete numeric values. Methods: Three alternatives for modeling of outcome probabilities are considered. Multinomial probabilities are based on different intercepts and slopes for probabilities of different outcome values. Ordinal probabilities are based on different intercepts and the same slope for probabilities of different outcome values. Censored Poisson probabilities are based on the same intercept and slope for probabilities of different outcome values. Parameters are estimated with extended linear mixed modeling maximizing a likelihood-like function based on the multivariate normal density that accounts for within-patient correlation. Formulas are provided for gradient vectors and Hessian matrices for estimating model parameters. The likelihood-like function is also used to compute cross-validation scores for alternative models and to control an adaptive modeling process for identifying possibly nonlinear functional relationships in predictors for probabilities and dispersions. Example analyses are provided of daily pain ratings for a cancer patient over a period of 97 days. Results: The censored Poisson approach is preferable for modeling these data, and presumably other data sets of this kind, because it generates a competitive model with fewer parameters in less time than the other two approaches. The generated probabilities for this model are distinctly nonlinear in time while the dispersions are distinctly nonconstant over time, demonstrating the need for adaptive modeling of such data. The analyses also address the dependence of these daily pain ratings on time and the daily numbers of pain flares. Probabilities and dispersions change differently over time for different numbers of pain flares. Conclusions: Adaptive modeling of daily pain ratings for individual cancer patients is an effective way to identify nonlinear relationships in time as well as in other predictors such as the number of pain flares.
文摘Software development is an important part of computer technology.only by ensuring the applicability and efficiency of the software can it really improve the efficiency of production and life,and truly inject new power into the economic benefits of the industry.As the theoretical basis of software development,the software development model directly determines the quality of software development.In this paper,starting with information technology as an important tool to improve modern management,it brings out the difficulties and pain points in the analysis of software development needs,and first puts forward the software development innovation model for building a composite core users.It takes core users with compound qualities and capabilities as the main line and guides the entire development process to enable both parties to communicate accurately and solve the pain points of demand communication,function optimization and project control to the greatest extent.Exploring application innovation in the software development model can promote innovation in the software industry.
基金Supported by the Service Public de Wallonie(SPW-EER,convention 8588,Belgium).
文摘BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.