BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of pr...BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
[Objectives]To investigate the effects of Visceral Manipulation combined with Enhanced Recovery after Surgery on postoperative recovery in patients undergoing gastrointestinal surgery,and to evaluate its impacts on in...[Objectives]To investigate the effects of Visceral Manipulation combined with Enhanced Recovery after Surgery on postoperative recovery in patients undergoing gastrointestinal surgery,and to evaluate its impacts on inflammatory stress response,gastrointestinal motility recovery,and blood oxygen levels.[Methods]A prospective randomized controlled design was adopted.Eighty patients undergoing gastrointestinal surgery from January 2022 to December 2023 were selected and randomly divided into an observation group(40 cases)and a control group(40 cases).The observation group received Visceral Manipulation therapy in addition to routine Enhanced Recovery after Surgery care,while the control group received only routine Enhanced Recovery after Surgery care.Clinical indicators,inflammatory factors(TNF-α,IL-6,hs-CRP),traumatic stress hormones(cortisol,epinephrine,norepinephrine),gastrointestinal motility indicators(GAS,MTL,GIP),and blood oxygen levels were measured and compared between the two groups on postoperative days 1,5,and 10.[Results]The observation group showed significantly better outcomes in postoperative abdominal distension,time to first flatus and defecation,and hospital stay compared to the control group(P<0.05).Inflammatory factors(TNF-α,IL-6,hs-CRP),traumatic stress hormones(cortisol,epinephrine,norepinephrine),and gastrointestinal motility indicators(GAS,MTL,GIP)were significantly improved in the observation group(P<0.05).Postoperative blood oxygen levels were also significantly higher in the observation group(P<0.05).[Conclusions]Visceral Manipulation combined with Enhanced Recovery after Surgery can significantly improve postoperative recovery in gastrointestinal surgery patients,alleviate inflammatory stress responses,promote gastrointestinal functional recovery,and enhance blood oxygen levels,demonstrating promising clinical application prospects.展开更多
Objective:To evaluate the dosing,efficacy and safety of the main antileishmanial agents amphotericin B(conventional or liposomal),pentavalent antimonials,miltefosine and paromomycin recommended for the treatment of vi...Objective:To evaluate the dosing,efficacy and safety of the main antileishmanial agents amphotericin B(conventional or liposomal),pentavalent antimonials,miltefosine and paromomycin recommended for the treatment of visceral leishmaniasis in children.Methods:The efficacy and safety of visceral leishmaniasis treatments in children were systematically reviewed using literature from PubMed,Cochrane,clinicaltrials.gov,and Google Scholar,focusing on randomised trials with separate pediatric data(published from 2000-2024).The risk of bias of selected trials was assessed using the revised Cochrane risk-of-bias tool for randomised trials(RoB 2).Reporting was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist.Results:Of 1186 records,only 7 were eligible for qualitative synthesis.Three trials exclusively included children.The treatment regimens studied showed high heterogeneity and lacked sufficient data for a meta-analysis.Most trial arms reported efficacies over 94%for children across different regimens.Miltefosine monotherapy showed the highest rate of late treatment failures,highlighting that allometric dosing is crucial to ensure proper drug exposure in children.Safety data for children were available in only three studies with varied reporting systems of adverse events.Although regimens in this review were generally considered to be safe in children,antimonial-related cardiac toxicity remains a threat.Conclusions:This review highlights the need for pediatric-specific trials,clear presentation of pediatric data,and systematic documentation of adverse events to enhance evidence for policy-making and pediatric guideline development.展开更多
Purpose:To investigate the clinical effects of improving adolescents’form anxiety after the intervention of visceral massage technique and form training.Methods:A total of 80 adolescent patients with scoliosis abnorm...Purpose:To investigate the clinical effects of improving adolescents’form anxiety after the intervention of visceral massage technique and form training.Methods:A total of 80 adolescent patients with scoliosis abnormalities were selected for this experiment,and they were intervened with form and body training and form and body training+visceral body acupressure techniques,and the anxiety and depression scores,spinal Cobb angle,vertebral body rotation of the parietal vertebrae,and the treatment efficiency were compared between the groups after the clinical interventions.Results:The anxiety and depression scores of patients in the form group were significantly higher than those of the combined group,P<0.05;the improvement of the Cobb angle and vertebral rotation of the parietal vertebrae of patients in the combined group was better than that of the form group,P<0.05;and the total effective rate of the treatment of patients in the form group was significantly lower than that of the combined group,P<0.05.Conclusion:After intervening in adolescents’abnormalities of form,patients were treated with a combination of the internal organs and body acupressure techniques and form training methods,and the results were compared between groups.After the joint intervention of the visceral massage technique and physical training,the patients’scoliosis and other physical problems were positively improved,and the psychological status of the patients was relatively adjusted to ensure their physical and mental health.展开更多
Type 2 diabetes mellitus(T2DM)is increasing among adolescents,but paediatric risk predictors are relatively underdeveloped.This study aimed to establish the associations of visceral adiposity index(VAI)and cardiorespi...Type 2 diabetes mellitus(T2DM)is increasing among adolescents,but paediatric risk predictors are relatively underdeveloped.This study aimed to establish the associations of visceral adiposity index(VAI)and cardiorespiratory fitness(CRF)with fasting plasma glucose in 418 Nigerian adolescents aged 11 years to 19 years.Using a cross-sectional design,participants were stratified by VAI and CRF tertiles to examine variations in impaired fasting glucose(IFG)risk.The findings of this study revealed significant gender differences:In the case of boys,high VAI and low CRF is associated with IFG,while no association was present in girls.CRF,measured by the 20-meter shuttle run,was a stronger predictor of IFG than VAI,suggesting that physical fitness is a protective factor against glucose dysreg-ulation.These findings point to VAI and CRF as useful,non-invasive predictors of risk for T2DM in youth,supporting school-based fitness programs that promote CRF and attenuate visceral adiposity,particularly in males.Future work must validate these predictors across various ethnic populations and identify other risk factors that can augment plans for early interventions aimed at the prevention of adolescent T2DM.展开更多
The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
BACKGROUND The annual incidence of gastric cancer in elderly patients is increasing.Despite the continuous progress in treatment methods,the prognosis of elderly patients remains poor,and postoperative complications a...BACKGROUND The annual incidence of gastric cancer in elderly patients is increasing.Despite the continuous progress in treatment methods,the prognosis of elderly patients remains poor,and postoperative complications are frequent.Obesity is believed to be associated with the risk of gastric cancer and postoperative prognosis;however,the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients remains unclear.AIM To explore the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients.METHODS A total of 163 elderly patients treated at the Affiliated Longyan First Hospital of Fujian Medical University after radical gastrectomy between January 2021 and January 2024 were enrolled.The patients'visceral and subcutaneous fat distributions were measured and divided into a high visceral fat area(VFA-H)group and a low visceral fat area(VFA-L)group,with a critical value of 100 cm^(2).The ttest andχ^(2) test were used to calculate and analyze the relationship between visceral fat area(VFA)and complications.Independent risk factors for postoperative complications were analyzed using binary logistic regression analysis.RESULTS Compared with the VFA-L group,the incidence of postoperative complications was higher in the VFA-H group(27.8%vs 6.4%,P<0.001),and the operation time was longer(268.55±63.41 vs 224.31±51.89,P<0.001).The amount of blood loss was more(163.77±105.27 mL vs 127.93±98.26 mL,P<0.001).Logistic regression analysis showed that VFA[odds ratio(OR):2.597,95%CI:1.479-4.853,P=0.004],total fat area(OR:1.655,95%CI:1.076-4.040,P=0.013),and the visceral subcutaneous fat area ratio(OR:2.046,95%CI:1.196-5.640,P=0.008)were independent risk factors for postoperative complications.CONCLUSION This study showed that postoperative complications are closely related to fat distribution in elderly patients with gastric cancer undergoing gastrectomy.A high VFA is associated by a high incidence of postoperative complications.展开更多
Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to ...Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial ...[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.展开更多
Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling ...Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors(PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.展开更多
Functional, or non-ulcer, dyspepsia （FD） is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that...Functional, or non-ulcer, dyspepsia （FD） is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.展开更多
BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(...BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.展开更多
In recent years,the use of fluorescence-guided surgery(FGS)to treat benign and malignant visceral,hepatobiliary and pancreatic neoplasms has significantly increased.FGS relies on the fluorescence signal emitted by inj...In recent years,the use of fluorescence-guided surgery(FGS)to treat benign and malignant visceral,hepatobiliary and pancreatic neoplasms has significantly increased.FGS relies on the fluorescence signal emitted by injected substances(fluorophores)after being illuminated by ad hoc laser sources to help guide the surgical procedure and provide the surgeon with real-time visualization of the fluorescent structures of interest that would be otherwise invisible.This review surveys and discusses the most common and emerging clinical applications of indocyanine green(ICG)-based fluorescence in visceral,hepatobiliary and pancreatic surgery.The analysis,findings,and discussion presented here rely on the authors'significant experience with this technique in their medical institutions,an up-to-date review of the most relevant articles published on this topic between 2014 and 2018,and lengthy discussions with key opinion leaders in the field during recent conferences and congresses.For each application,the benefits and limitations of this technique,as well as applicable future directions,are described.The imaging of fluorescence emitted by ICG is a simple,fast,relatively inexpensive,and harmless tool with numerous different applications in surgery for both neoplasms and benign pathologies of the visceral and hepatobiliary systems.The ever-increasing availability of visual systems that can utilize this tool will transform some of these applications into the standard of care in the near future.Further studies are needed to evaluate the strengths and weaknesses of each application of ICG-based fluorescence imaging in abdominal surgery.展开更多
AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male Sprague...AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.展开更多
Objective To evaluate the sensitivity and specificity of body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) measurements in diagnosing abdominal visceral obesity. Methods BMI, WC, and WHR wer...Objective To evaluate the sensitivity and specificity of body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) measurements in diagnosing abdominal visceral obesity. Methods BMI, WC, and WHR were assessed in 690 Chinese adults (305 men and 385 women) and compared with magnetic resonance imaging (MRI) measurements of abdominal visceral adipose tissue (VA). Receiver operating characteristic (ROC) curves were generated and used to determine the threshold point for each anthropometric parameter. Results 1) MRI showed that 61.7% of overweight/obese individuals (BMI≥25 kg/m2) and 14.2% of normal weight (BMI<25 kg/m2) individuals had abdominal visceral obesity (VA≥100 cm2). 2) VA was positively correlated with each anthropometric variable, of which WC showed the highest correlation (r=0.73-0.77, P<0.001). 3) The best cut-off points for assessing abdominal visceral obesity were as followed: BMI of 26 kg/m2, WC of 90 cm, and WHR of 0.93, with WC being the most sensitive and specific factor. 4) Among subjects with BMI≥28 kg/m2 or WC≥95 cm, 95% of men and 90% of women appeared to have abdominal visceral obesity. Conclusion Measurements of BMI, WC, and WHR can be used in the prediction of abdominal visceral obesity, of which WC was the one with better accuracy.展开更多
BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little u...BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.展开更多
AIM： To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome （IBS）. Dysfuncti...AIM： To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome （IBS）. Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function. METHODS： Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities （visual analogue scale, VAS 0-100） during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously （heterotopic stimulation） were recorded in 40 female patients with IBS and 20 female healthy controls. RESULTS： Rectal hypersensitivity （defined by 95% Cl of controls） was seen in 21 （53%）, somatic hypersensitivity in 22 （55%） and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 （-11 to -1） in controls, but increased rectal pain by 2 （-3 to ＋6） in all IBS patients （P 〈 0.05） and by 8 （-2 to ＋19） in IBS patients with somatic and visceral hypersensitivity （P 〈 0.02）. CONCLUSION： A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.展开更多
AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied...AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.展开更多
文摘BACKGROUND Elderly patients with colorectal cancer(CRC)can judge the risk of postoperative complications and oncological outcomes due to visceral obesity,which can provide data reference for the early prediction of prognosis.AIM To explore the effect of visceral obesity on postoperative complications and oncological outcomes in elderly patients with CRC.METHODS A total of 150 elderly patients who underwent radical surgery for CRC at Inner Mongolia Medical University and Inner Mongolia Autonomous Region People’s Hospital from January 2021 to June 2024 were retrospectively analyzed.Patients were divided into the abdominal[visceral fat area(VFA)≥100.00 cm^(2),n=80]and non-abdominal(VFA<100.00 cm^(2),n=70)obesity groups according to the VFA measured by preoperative computed tomography.The two groups showed no significant differences in age,sex,tumor location,tumor-node-metastasis stage,and underlying disease(P>0.05).All patients underwent standardized laparoscopic assisted surgery and received unified perioperative management.Complications,nutritional status,changes in biochemical indicators,and tumor recurrence and metastasis were evaluated postoperatively.RESULTS The overall incidence of postoperative complications was significantly higher in the abdominal obesity group than in the non-abdominal obesity group(P<0.05).The pulmonary infection on postoperative day(POD)3(P=0.038),anastomotic leakage on POD 7(P=0.042),and moderate-to-severe complications(Clavien-Dindo class III,P=0.03)were significantly different.With respect to biochemical indicators,the white blood cell count,neutrophil percentage,and C-reactive protein level in the abdominal obesity group continuously increased after surgery(P<0.05);the albumin level on POD 1 was even lower(P=0.024).Regarding tumor markers,carcinoembryonic antigen(P=0.039)and carbohydrate antigen 19-9(P=0.048)levels were significantly higher in the abdominal obesity group at 3 months after surgery,and local recurrence rates were higher than those in the non-abdominal obesity group at 30 days and 3 months after surgery(P<0.05).Abdominal obesity was an independent risk factor for postoperative complications(odds ratio:3.843,P=0.001),overall survival[hazard ratio(HR):1.937,P=0.011],and disease-free survival(HR:1.769,P=0.018).CONCLUSION Visceral obesity significantly increases the risk of postoperative complications in elderly patients with CRC and may adversely affect short-term tumor prognosis.Preoperative risk identification and interventions for abdominal obesity should be strengthened to improve perioperative safety and postoperative rehabilitation quality.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
基金Supported by Guiding Project of Shiyan City,Hubei Province in 2022(22Y30).
文摘[Objectives]To investigate the effects of Visceral Manipulation combined with Enhanced Recovery after Surgery on postoperative recovery in patients undergoing gastrointestinal surgery,and to evaluate its impacts on inflammatory stress response,gastrointestinal motility recovery,and blood oxygen levels.[Methods]A prospective randomized controlled design was adopted.Eighty patients undergoing gastrointestinal surgery from January 2022 to December 2023 were selected and randomly divided into an observation group(40 cases)and a control group(40 cases).The observation group received Visceral Manipulation therapy in addition to routine Enhanced Recovery after Surgery care,while the control group received only routine Enhanced Recovery after Surgery care.Clinical indicators,inflammatory factors(TNF-α,IL-6,hs-CRP),traumatic stress hormones(cortisol,epinephrine,norepinephrine),gastrointestinal motility indicators(GAS,MTL,GIP),and blood oxygen levels were measured and compared between the two groups on postoperative days 1,5,and 10.[Results]The observation group showed significantly better outcomes in postoperative abdominal distension,time to first flatus and defecation,and hospital stay compared to the control group(P<0.05).Inflammatory factors(TNF-α,IL-6,hs-CRP),traumatic stress hormones(cortisol,epinephrine,norepinephrine),and gastrointestinal motility indicators(GAS,MTL,GIP)were significantly improved in the observation group(P<0.05).Postoperative blood oxygen levels were also significantly higher in the observation group(P<0.05).[Conclusions]Visceral Manipulation combined with Enhanced Recovery after Surgery can significantly improve postoperative recovery in gastrointestinal surgery patients,alleviate inflammatory stress responses,promote gastrointestinal functional recovery,and enhance blood oxygen levels,demonstrating promising clinical application prospects.
文摘Objective:To evaluate the dosing,efficacy and safety of the main antileishmanial agents amphotericin B(conventional or liposomal),pentavalent antimonials,miltefosine and paromomycin recommended for the treatment of visceral leishmaniasis in children.Methods:The efficacy and safety of visceral leishmaniasis treatments in children were systematically reviewed using literature from PubMed,Cochrane,clinicaltrials.gov,and Google Scholar,focusing on randomised trials with separate pediatric data(published from 2000-2024).The risk of bias of selected trials was assessed using the revised Cochrane risk-of-bias tool for randomised trials(RoB 2).Reporting was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist.Results:Of 1186 records,only 7 were eligible for qualitative synthesis.Three trials exclusively included children.The treatment regimens studied showed high heterogeneity and lacked sufficient data for a meta-analysis.Most trial arms reported efficacies over 94%for children across different regimens.Miltefosine monotherapy showed the highest rate of late treatment failures,highlighting that allometric dosing is crucial to ensure proper drug exposure in children.Safety data for children were available in only three studies with varied reporting systems of adverse events.Although regimens in this review were generally considered to be safe in children,antimonial-related cardiac toxicity remains a threat.Conclusions:This review highlights the need for pediatric-specific trials,clear presentation of pediatric data,and systematic documentation of adverse events to enhance evidence for policy-making and pediatric guideline development.
文摘Purpose:To investigate the clinical effects of improving adolescents’form anxiety after the intervention of visceral massage technique and form training.Methods:A total of 80 adolescent patients with scoliosis abnormalities were selected for this experiment,and they were intervened with form and body training and form and body training+visceral body acupressure techniques,and the anxiety and depression scores,spinal Cobb angle,vertebral body rotation of the parietal vertebrae,and the treatment efficiency were compared between the groups after the clinical interventions.Results:The anxiety and depression scores of patients in the form group were significantly higher than those of the combined group,P<0.05;the improvement of the Cobb angle and vertebral rotation of the parietal vertebrae of patients in the combined group was better than that of the form group,P<0.05;and the total effective rate of the treatment of patients in the form group was significantly lower than that of the combined group,P<0.05.Conclusion:After intervening in adolescents’abnormalities of form,patients were treated with a combination of the internal organs and body acupressure techniques and form training methods,and the results were compared between groups.After the joint intervention of the visceral massage technique and physical training,the patients’scoliosis and other physical problems were positively improved,and the psychological status of the patients was relatively adjusted to ensure their physical and mental health.
文摘Type 2 diabetes mellitus(T2DM)is increasing among adolescents,but paediatric risk predictors are relatively underdeveloped.This study aimed to establish the associations of visceral adiposity index(VAI)and cardiorespiratory fitness(CRF)with fasting plasma glucose in 418 Nigerian adolescents aged 11 years to 19 years.Using a cross-sectional design,participants were stratified by VAI and CRF tertiles to examine variations in impaired fasting glucose(IFG)risk.The findings of this study revealed significant gender differences:In the case of boys,high VAI and low CRF is associated with IFG,while no association was present in girls.CRF,measured by the 20-meter shuttle run,was a stronger predictor of IFG than VAI,suggesting that physical fitness is a protective factor against glucose dysreg-ulation.These findings point to VAI and CRF as useful,non-invasive predictors of risk for T2DM in youth,supporting school-based fitness programs that promote CRF and attenuate visceral adiposity,particularly in males.Future work must validate these predictors across various ethnic populations and identify other risk factors that can augment plans for early interventions aimed at the prevention of adolescent T2DM.
文摘The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
文摘BACKGROUND The annual incidence of gastric cancer in elderly patients is increasing.Despite the continuous progress in treatment methods,the prognosis of elderly patients remains poor,and postoperative complications are frequent.Obesity is believed to be associated with the risk of gastric cancer and postoperative prognosis;however,the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients remains unclear.AIM To explore the effect of visceral fat distribution on postoperative complications of gastric cancer in elderly patients.METHODS A total of 163 elderly patients treated at the Affiliated Longyan First Hospital of Fujian Medical University after radical gastrectomy between January 2021 and January 2024 were enrolled.The patients'visceral and subcutaneous fat distributions were measured and divided into a high visceral fat area(VFA-H)group and a low visceral fat area(VFA-L)group,with a critical value of 100 cm^(2).The ttest andχ^(2) test were used to calculate and analyze the relationship between visceral fat area(VFA)and complications.Independent risk factors for postoperative complications were analyzed using binary logistic regression analysis.RESULTS Compared with the VFA-L group,the incidence of postoperative complications was higher in the VFA-H group(27.8%vs 6.4%,P<0.001),and the operation time was longer(268.55±63.41 vs 224.31±51.89,P<0.001).The amount of blood loss was more(163.77±105.27 mL vs 127.93±98.26 mL,P<0.001).Logistic regression analysis showed that VFA[odds ratio(OR):2.597,95%CI:1.479-4.853,P=0.004],total fat area(OR:1.655,95%CI:1.076-4.040,P=0.013),and the visceral subcutaneous fat area ratio(OR:2.046,95%CI:1.196-5.640,P=0.008)were independent risk factors for postoperative complications.CONCLUSION This study showed that postoperative complications are closely related to fat distribution in elderly patients with gastric cancer undergoing gastrectomy.A high VFA is associated by a high incidence of postoperative complications.
基金supported by the National Key Research and Development Program of China(2021YFD2100700)the National Natural Science Foundation of China(32021005)+1 种基金the 111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
基金Supported by Science and Technology Plan Project of Zhongshan City(2022B1126).
文摘[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.
基金Supported by University Research Fund Doctoral Projects(BOF-DOCPRO),No.DOCPRO4 2014/ID 2964Research Foundation Flanders(FWO),No.G034113N
文摘Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors(PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.
文摘Functional, or non-ulcer, dyspepsia （FD） is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.
基金Supported by the National Key Technology Support Program during "12th Five-Year Plan"Period of China,No.2014BAI08B00the Leapforward Development Program for Beijing Biopharmaceutical Industry(G20),No.Z171100001717008
文摘BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.
文摘In recent years,the use of fluorescence-guided surgery(FGS)to treat benign and malignant visceral,hepatobiliary and pancreatic neoplasms has significantly increased.FGS relies on the fluorescence signal emitted by injected substances(fluorophores)after being illuminated by ad hoc laser sources to help guide the surgical procedure and provide the surgeon with real-time visualization of the fluorescent structures of interest that would be otherwise invisible.This review surveys and discusses the most common and emerging clinical applications of indocyanine green(ICG)-based fluorescence in visceral,hepatobiliary and pancreatic surgery.The analysis,findings,and discussion presented here rely on the authors'significant experience with this technique in their medical institutions,an up-to-date review of the most relevant articles published on this topic between 2014 and 2018,and lengthy discussions with key opinion leaders in the field during recent conferences and congresses.For each application,the benefits and limitations of this technique,as well as applicable future directions,are described.The imaging of fluorescence emitted by ICG is a simple,fast,relatively inexpensive,and harmless tool with numerous different applications in surgery for both neoplasms and benign pathologies of the visceral and hepatobiliary systems.The ever-increasing availability of visual systems that can utilize this tool will transform some of these applications into the standard of care in the near future.Further studies are needed to evaluate the strengths and weaknesses of each application of ICG-based fluorescence imaging in abdominal surgery.
基金Supported by National Natural Science Foundation of China,No.81230024,No.81471137(to GYX)and No.31400947(to HHZ)Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.
文摘Objective To evaluate the sensitivity and specificity of body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) measurements in diagnosing abdominal visceral obesity. Methods BMI, WC, and WHR were assessed in 690 Chinese adults (305 men and 385 women) and compared with magnetic resonance imaging (MRI) measurements of abdominal visceral adipose tissue (VA). Receiver operating characteristic (ROC) curves were generated and used to determine the threshold point for each anthropometric parameter. Results 1) MRI showed that 61.7% of overweight/obese individuals (BMI≥25 kg/m2) and 14.2% of normal weight (BMI<25 kg/m2) individuals had abdominal visceral obesity (VA≥100 cm2). 2) VA was positively correlated with each anthropometric variable, of which WC showed the highest correlation (r=0.73-0.77, P<0.001). 3) The best cut-off points for assessing abdominal visceral obesity were as followed: BMI of 26 kg/m2, WC of 90 cm, and WHR of 0.93, with WC being the most sensitive and specific factor. 4) Among subjects with BMI≥28 kg/m2 or WC≥95 cm, 95% of men and 90% of women appeared to have abdominal visceral obesity. Conclusion Measurements of BMI, WC, and WHR can be used in the prediction of abdominal visceral obesity, of which WC was the one with better accuracy.
基金the National Natural Science Foundation of China,No.81800489Shenzhen Health and Family Planning System Research Project,No.SZXJ2017030Technical Research and Development Project of Shenzhen,Nos.JCYJ20170307100538697 and JCYJ20170307100911479
文摘BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.
基金the Brain-Gut Research Group, Berne, Switzerland
文摘AIM： To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome （IBS）. Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function. METHODS： Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities （visual analogue scale, VAS 0-100） during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously （heterotopic stimulation） were recorded in 40 female patients with IBS and 20 female healthy controls. RESULTS： Rectal hypersensitivity （defined by 95% Cl of controls） was seen in 21 （53%）, somatic hypersensitivity in 22 （55%） and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 （-11 to -1） in controls, but increased rectal pain by 2 （-3 to ＋6） in all IBS patients （P 〈 0.05） and by 8 （-2 to ＋19） in IBS patients with somatic and visceral hypersensitivity （P 〈 0.02）. CONCLUSION： A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.
基金Supported by National Basic Research Program of China(973 Program)No.2009CB522900 and No.2015CB554501National Natural Science Foundation of China,No.30973784
文摘AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.
