Flexible strain sensors are promising in sensing minuscule mechanical signals,and thereby widely used in various advanced fields.However,the effective integration of hypersensitivity and highly selective response into...Flexible strain sensors are promising in sensing minuscule mechanical signals,and thereby widely used in various advanced fields.However,the effective integration of hypersensitivity and highly selective response into one flexible strain sensor remains a huge challenge.Herein,inspired by the hysteresis strategy of the scorpion slit receptor,a bio-inspired flexible strain sensor(BFSS)with parallel through-slit arrays is designed and fabricated.Specifically,BFSS consists of conductive monolayer graphene and viscoelastic styrene–isoprene–styrene block copolymer.Under the synergistic effect of the bio-inspired slit structures and flexible viscoelastic materials,BFSS can achieve both hypersensitivity and highly selective frequency response.Remarkably,the BFSS exhibits a high gage factor of 657.36,and a precise identification of vibration frequencies at a resolution of 0.2 Hz through undergoing different morphological changes to high-frequency vibration and low-frequency vibration.Moreover,the BFSS possesses a wide frequency detection range(103 Hz)and stable durability(1000 cycles).It can sense and recognize vibration signals with different characteristics,including the frequency,amplitude,and waveform.This work,which turns the hysteresis effect into a"treasure,"can provide new design ideas for sensors for potential applications including human–computer interaction and health monitoring of mechanical equipment.展开更多
The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzin...The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.展开更多
Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)...Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].展开更多
BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diar...BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.展开更多
Nucleotide-binding site leucine-rich repeat receptors (NBS-LRR/NLRs) are crucial intracellular immune proteins in plants. Previous article reported a novel NLR protein SUT1 (SUPPRESSORS OF TOPP4-1, 1), which is involv...Nucleotide-binding site leucine-rich repeat receptors (NBS-LRR/NLRs) are crucial intracellular immune proteins in plants. Previous article reported a novel NLR protein SUT1 (SUPPRESSORS OF TOPP4-1, 1), which is involved in autoimmunity initiated by type one protein phosphatase 4 mutation (topp4-1) in Arabidopsis, however, its role in planta is still unclear. This study employed Nicotiana benthamiana, a model platform, to conduct an overall structural and functional analysis of SUT1 protein. The transient expression results revealed that SUT1 is a typical CNL (CC-NBS-LRR) receptor, both fluorescence data and biochemical results showed the protein is mainly anchored on the plasma membrane due to its N-terminal acylation site. Further truncation experiments announced that its CC (coiled-coil) domain possessed cell-death-inducing activity. The outcomes of point mutations analysis revealed that not only the CC domain, but also the full-length SUT1 protein, whose function and subcellular localization are influenced by highly conserved hydrophobic residues. These research outcomes provided favorable clues for elucidating the activation mechanism of SUT1.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is a global problem,causing significant morbidity and mortality.Furazolidone is recommended to eradicate H.pylori infections in China owing to the highly associated an...BACKGROUND Helicobacter pylori(H.pylori)infection is a global problem,causing significant morbidity and mortality.Furazolidone is recommended to eradicate H.pylori infections in China owing to the highly associated antibiotic resistance.CASE SUMMARY This article presents two cases of lung injury caused by furazolidone treatment of H.pylori infection and the relevant literature review.Two patients developed symptoms,including fever,cough,and fatigue after receiving a course of furazolidone for H.pylori infection.Chest computed tomography showed bilateral interstitial infiltrates.Laboratory studies revealed elevated blood eosinophil count.After discontinuing furazolidone with or without the use of corticosteroids,the symptoms improved rapidly.A PubMed database literature search revealed three reported cases of lung injury suggestive of furazolidone-induced pulmonary toxicity.CONCLUSION Clinicians should be aware of the side effects associated with the administration of furazolidone to eradicate H.pylori infection.展开更多
We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground.Etiologic diagnosis played a key role in this case.Systemic examinations ruled out systemic autoimmune dis...We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground.Etiologic diagnosis played a key role in this case.Systemic examinations ruled out systemic autoimmune diseases,tumors,and infections as the cause of scleritis and suggested that the disease was caused by a local delayedtype hypersensitivity(DTH)induced by ocular trauma and was non-infectious.Still,the right epididymitis was infectious.Both conditions were treated successfully using steroids and antibiotics,respectively.Thus,early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.展开更多
Although Blufensins(Bln)have important functions in the response of plants to biotic stress the precise functioning of Bln in wheat remains largely unknown.Here we isolated a Bln gene(TaBln4)from Suwon 11 infected by ...Although Blufensins(Bln)have important functions in the response of plants to biotic stress the precise functioning of Bln in wheat remains largely unknown.Here we isolated a Bln gene(TaBln4)from Suwon 11 infected by Puccinia striiformis f.sp.tritici(Pst).Expression of TaBln4 increased in host plants at the early stage of infection with a virulent Pst race(CYR31)but was unchanged in response to infection by an avirulent race(CYR23).Transcription levels of TaBln4 were also regulated by hormone and abiotic stresses.Expression of TaBln4 in tobacco leaves suppressed Bax-induced programmed cell death.Knockdown of TaBln4 by virus-induced gene silencing inhibited colonization of race CYR31 by increasing the accumulation of H2O2 and formation of hypersensitive responses(HR).Transient overexpression of TaBln4 by a transient overexpression system(BSMV-VOX)increased the susceptibility of wheat to CYR31.Results from bimolecular fluorescence complementation and pull-down assays demonstrated that TaBLN4 interacted with calmodulin.Taken together,our results suggest that TaBln4 negatively regulates resistance in wheat to Pst in a reactive oxygen species(ROS)-and HR-dependent manner.展开更多
Background: The available data on cryptogenic chronic hypersensitivity pneumonitis (ccHP) indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the rol...Background: The available data on cryptogenic chronic hypersensitivity pneumonitis (ccHP) indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe and progressive disease. Patients and Methods: A total of 9 patients were included in the study. They had criteria for ccHP viz. 1) clinical features of cryptogenic progressive restrictive lung disease, 2) high-resolution computed tomographic pulmonary abnormalities, and 3) bronchoalveolar lavage lymphocytosis (>30%). The regimen consisted of an initial induction phase of 3-month Solumedrol 1 g IV daily for 3 days followed by 1 month of Prednisone (P) 60 mg/day to tapered down to discontinuation by 3rd month. They also had received Mycophenolate mofetil (MMF) 1 g twice daily for 3 months. This stage was followed by a maintenance phase of yearly Rituximab infusions (1 g followed by 1 g 2 weeks later). Results: compared to their previous 6 months deterioration;all patients showed significant improvement in their forced vital volume, diffusion capacity for carbon monoxide, 6-minutes-walk after the induction phase (at 3 months) which improved further at 15 months with Rituximab therapy. Conclusion: After 3-month induction therapy with P and MMF;yearly R treatment is a safe, practical and effective long-term therapy for ccHP.展开更多
Allergic reactions in neurosurgical procedures are uncommon,but they are detrimental to a patient’s prognosis and recovery.By synthesizing data collected from other surgical fields,possible triggers and alternatives ...Allergic reactions in neurosurgical procedures are uncommon,but they are detrimental to a patient’s prognosis and recovery.By synthesizing data collected from other surgical fields,possible triggers and alternatives have been identified.Current treatment guidelines involve stabilizing the patient in emergency situations,symptom management,and identification of causative allergens.Preoperative allergy screening is uncommon due to the low prevalence of perioperative hypersensitivity reactions.However,preoperative questionnaire screening can identify when preoperative allergy screening,premedication,or use of a material alternative is necessary.Greater emphasis on material alternatives,increased preoperative screening,and more data can improve the prognosis of neurosurgical patients at risk of perioperative allergic complications.展开更多
Objective To present a rare case of skin allergic reaction to gadobutrol,a magnetic resonance imaging(MRI)contrast agent,in a 37-year-old man.Methods The adverse reactions of gadobutrol were analyzed combined with the...Objective To present a rare case of skin allergic reaction to gadobutrol,a magnetic resonance imaging(MRI)contrast agent,in a 37-year-old man.Methods The adverse reactions of gadobutrol were analyzed combined with the instructions and related literatures.Results and Conclusion The presence of this patient is consistent with the adverse reactions in the instructions of gadobutrol.The incidence of ADR in gadobutrol is considered to be low,although sometimes patients report a hypersensitivity reaction when undergoing MRI.There are only a few cases of immediate adverse reactions to gadobutrol.However,we should improve the ability of medical staff to use drugs safely and take preventive measures.展开更多
AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period...AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.展开更多
AIM:To observe the analgesic effects of moxibustion in rats with chronic visceral hyperalgesia and its influence on the concentration of dynorphin(Dyn) and endomorphin(EM) in spinal cord.METHODS:The rat model of chron...AIM:To observe the analgesic effects of moxibustion in rats with chronic visceral hyperalgesia and its influence on the concentration of dynorphin(Dyn) and endomorphin(EM) in spinal cord.METHODS:The rat model of chronic visceral hyperalgesia was established by colorectal distention(CRD).In moxibustion(MX) group,moxibustion was applied once daily for 7 d;in sham moxibustion(SM) group,moxibustion was given to the same acupoints but with the nonsmoldered end of the moxa stick.Model control(MC) group and normal control group were also studied.The scoring system of abdominal withdrawal reflex was used to evaluate visceral pain for behavioral assessment.Enzyme linked immunosorbent assay was performed to determine the concentrations of Dyn and EM in spinal cord.RESULTS:Moxibustion significantly decreased visceral pain to CRD in this rat model,and no significant difference was detected between the SM group and the MC group.In MX group,moxibustion also increased the concentrations of Dyn and EM in spinal cord,and no significant difference was found between the SM group and the MC group.CONCLUSION:Moxibustion therapy can significantly enhance the pain threshold of rats with chronic visceral hyperalgesia,and the effect may be closely related to the increased concentration of Dyn and EM in spinal cord.展开更多
Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,...Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.展开更多
BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that inte...BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1β,IL-18,and resistance-like moleculeβby promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl-aspartate-specific proteinase 1(Caspase-1).The relative DNA abundances of Lactobacillus,Bifidobacteria,Faecalibacterium prausnitzii,and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6,ASC,and Caspase-1 in the colon.CONCLUSION These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling.展开更多
Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain ...Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.GERD symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors involved.Prolonged contact of the esophageal mucosa with the refluxed content,probably caused by a defective anti-reflux barrier and luminal clearance mechanisms,would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium.Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid exposure.Meanwhile,specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD,explaining,in part,the genesis of esophagitis in a subset of patients.Despite these findings,which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD,the relationship between the hypersensitivity and esophageal inflammation is not clear.Moreover,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux disease.This summary aims to explore the inflammatory pathway involved in GERD pathogenesis,to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.展开更多
Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may...Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may be multifactorial,as is the pathophysiology,which is attributed to alterations in gastrointestinal motility,visceral hypersensitivity,intestinal microbiota,gut epithelium and immune function,dysfunction of the brain-gut axis or certain psychosocial factors.Current therapeutic strategies are often unsatisfactory.There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS.Probiotics are living organisms which,when ingested in certain numbers,exert health benefits beyond inherent basic nutrition.Probiotics have numerous positive effects in the gastrointestinal tract.Recently,many studies have suggested that probiotics are effective in the treatment of IBS.The mechanisms of probiotics in IBS are very complex.The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.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
基金This work was supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(Grant No.52021003)National Natural Science Foundation of China(Grant No.51835006)+6 种基金the National Natural Science Foundation of China(Grant Nos.52222509,52105301,U19A20103)Jilin University Science and Technology Innovative Research Team(Grant No.2020TD-03)Interdisciplinary Integration and Innovation Project of JLU(Grant No.JLUXKJC2021ZZ03)the Natural Science Foundation of Jilin Province(Grant No.20220101220JC)Education Department of Jilin Province(Grant No.JJKH20220979KJ)Graduate Innovation Fund of Jilin University(2023CX077)supported by“Fundamental Research Funds for the Central Universities.”。
文摘Flexible strain sensors are promising in sensing minuscule mechanical signals,and thereby widely used in various advanced fields.However,the effective integration of hypersensitivity and highly selective response into one flexible strain sensor remains a huge challenge.Herein,inspired by the hysteresis strategy of the scorpion slit receptor,a bio-inspired flexible strain sensor(BFSS)with parallel through-slit arrays is designed and fabricated.Specifically,BFSS consists of conductive monolayer graphene and viscoelastic styrene–isoprene–styrene block copolymer.Under the synergistic effect of the bio-inspired slit structures and flexible viscoelastic materials,BFSS can achieve both hypersensitivity and highly selective frequency response.Remarkably,the BFSS exhibits a high gage factor of 657.36,and a precise identification of vibration frequencies at a resolution of 0.2 Hz through undergoing different morphological changes to high-frequency vibration and low-frequency vibration.Moreover,the BFSS possesses a wide frequency detection range(103 Hz)and stable durability(1000 cycles).It can sense and recognize vibration signals with different characteristics,including the frequency,amplitude,and waveform.This work,which turns the hysteresis effect into a"treasure,"can provide new design ideas for sensors for potential applications including human–computer interaction and health monitoring of mechanical equipment.
基金the Zhejiang Natural Science Foundation,China(Grant No.LY21C130004)the Key Research and Development Program of Zhejiang Province,China(Grant No.2021C02056-3)+1 种基金the Central Public-Interest Scientific Institution Basal Research Fund,China(Grant No.CPSIBRF-CNRRI-202202)the Agricultural Science and Technology Innovation Program,China(Grant No.CAASASTIP-2021-CNRRI).
文摘The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.
基金supported by the National Natural Science Foundation(81871691)the Beijing Municipal Natural Science Foundation(KZ202110025034).
文摘Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].
基金The Health Commission of Jinshan District,Shanghai,China,No.JSKJ-KTMS-2019-01The Youth Research Foundation of Jinshan Hospital of Fudan University,No.JYQN-JC-202101 and No.JYQN-JC-202216The Reserve Discipline Construction of Jinshan Hospital of Fudan University,No.HBXK-2021-2.
文摘BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.
文摘Nucleotide-binding site leucine-rich repeat receptors (NBS-LRR/NLRs) are crucial intracellular immune proteins in plants. Previous article reported a novel NLR protein SUT1 (SUPPRESSORS OF TOPP4-1, 1), which is involved in autoimmunity initiated by type one protein phosphatase 4 mutation (topp4-1) in Arabidopsis, however, its role in planta is still unclear. This study employed Nicotiana benthamiana, a model platform, to conduct an overall structural and functional analysis of SUT1 protein. The transient expression results revealed that SUT1 is a typical CNL (CC-NBS-LRR) receptor, both fluorescence data and biochemical results showed the protein is mainly anchored on the plasma membrane due to its N-terminal acylation site. Further truncation experiments announced that its CC (coiled-coil) domain possessed cell-death-inducing activity. The outcomes of point mutations analysis revealed that not only the CC domain, but also the full-length SUT1 protein, whose function and subcellular localization are influenced by highly conserved hydrophobic residues. These research outcomes provided favorable clues for elucidating the activation mechanism of SUT1.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is a global problem,causing significant morbidity and mortality.Furazolidone is recommended to eradicate H.pylori infections in China owing to the highly associated antibiotic resistance.CASE SUMMARY This article presents two cases of lung injury caused by furazolidone treatment of H.pylori infection and the relevant literature review.Two patients developed symptoms,including fever,cough,and fatigue after receiving a course of furazolidone for H.pylori infection.Chest computed tomography showed bilateral interstitial infiltrates.Laboratory studies revealed elevated blood eosinophil count.After discontinuing furazolidone with or without the use of corticosteroids,the symptoms improved rapidly.A PubMed database literature search revealed three reported cases of lung injury suggestive of furazolidone-induced pulmonary toxicity.CONCLUSION Clinicians should be aware of the side effects associated with the administration of furazolidone to eradicate H.pylori infection.
基金Supported by Beijing Natural Science Foundation(7202229).
文摘We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground.Etiologic diagnosis played a key role in this case.Systemic examinations ruled out systemic autoimmune diseases,tumors,and infections as the cause of scleritis and suggested that the disease was caused by a local delayedtype hypersensitivity(DTH)induced by ocular trauma and was non-infectious.Still,the right epididymitis was infectious.Both conditions were treated successfully using steroids and antibiotics,respectively.Thus,early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.
基金supported by the National Key Research and Development Program of China(2021YFD1401000)the International Science and Technology Cooperation Project of Shaanxi Provincial Key R&D Plan-Key Project(2020KWZ-009)+1 种基金the Shaanxi Innovation Team Project(2018TD-004)the 111 Project of the Ministry of Education of China(B07049).
文摘Although Blufensins(Bln)have important functions in the response of plants to biotic stress the precise functioning of Bln in wheat remains largely unknown.Here we isolated a Bln gene(TaBln4)from Suwon 11 infected by Puccinia striiformis f.sp.tritici(Pst).Expression of TaBln4 increased in host plants at the early stage of infection with a virulent Pst race(CYR31)but was unchanged in response to infection by an avirulent race(CYR23).Transcription levels of TaBln4 were also regulated by hormone and abiotic stresses.Expression of TaBln4 in tobacco leaves suppressed Bax-induced programmed cell death.Knockdown of TaBln4 by virus-induced gene silencing inhibited colonization of race CYR31 by increasing the accumulation of H2O2 and formation of hypersensitive responses(HR).Transient overexpression of TaBln4 by a transient overexpression system(BSMV-VOX)increased the susceptibility of wheat to CYR31.Results from bimolecular fluorescence complementation and pull-down assays demonstrated that TaBLN4 interacted with calmodulin.Taken together,our results suggest that TaBln4 negatively regulates resistance in wheat to Pst in a reactive oxygen species(ROS)-and HR-dependent manner.
文摘Background: The available data on cryptogenic chronic hypersensitivity pneumonitis (ccHP) indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe and progressive disease. Patients and Methods: A total of 9 patients were included in the study. They had criteria for ccHP viz. 1) clinical features of cryptogenic progressive restrictive lung disease, 2) high-resolution computed tomographic pulmonary abnormalities, and 3) bronchoalveolar lavage lymphocytosis (>30%). The regimen consisted of an initial induction phase of 3-month Solumedrol 1 g IV daily for 3 days followed by 1 month of Prednisone (P) 60 mg/day to tapered down to discontinuation by 3rd month. They also had received Mycophenolate mofetil (MMF) 1 g twice daily for 3 months. This stage was followed by a maintenance phase of yearly Rituximab infusions (1 g followed by 1 g 2 weeks later). Results: compared to their previous 6 months deterioration;all patients showed significant improvement in their forced vital volume, diffusion capacity for carbon monoxide, 6-minutes-walk after the induction phase (at 3 months) which improved further at 15 months with Rituximab therapy. Conclusion: After 3-month induction therapy with P and MMF;yearly R treatment is a safe, practical and effective long-term therapy for ccHP.
文摘Allergic reactions in neurosurgical procedures are uncommon,but they are detrimental to a patient’s prognosis and recovery.By synthesizing data collected from other surgical fields,possible triggers and alternatives have been identified.Current treatment guidelines involve stabilizing the patient in emergency situations,symptom management,and identification of causative allergens.Preoperative allergy screening is uncommon due to the low prevalence of perioperative hypersensitivity reactions.However,preoperative questionnaire screening can identify when preoperative allergy screening,premedication,or use of a material alternative is necessary.Greater emphasis on material alternatives,increased preoperative screening,and more data can improve the prognosis of neurosurgical patients at risk of perioperative allergic complications.
文摘Objective To present a rare case of skin allergic reaction to gadobutrol,a magnetic resonance imaging(MRI)contrast agent,in a 37-year-old man.Methods The adverse reactions of gadobutrol were analyzed combined with the instructions and related literatures.Results and Conclusion The presence of this patient is consistent with the adverse reactions in the instructions of gadobutrol.The incidence of ADR in gadobutrol is considered to be low,although sometimes patients report a hypersensitivity reaction when undergoing MRI.There are only a few cases of immediate adverse reactions to gadobutrol.However,we should improve the ability of medical staff to use drugs safely and take preventive measures.
文摘AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.
基金Supported by The National Basic Research Program of China,973 Program,No 2009CB522900Scientific Research Grants of Shanghai Health Bureau,No 2009209Shanghai Leading Academic Discipline Project,No S30304
文摘AIM:To observe the analgesic effects of moxibustion in rats with chronic visceral hyperalgesia and its influence on the concentration of dynorphin(Dyn) and endomorphin(EM) in spinal cord.METHODS:The rat model of chronic visceral hyperalgesia was established by colorectal distention(CRD).In moxibustion(MX) group,moxibustion was applied once daily for 7 d;in sham moxibustion(SM) group,moxibustion was given to the same acupoints but with the nonsmoldered end of the moxa stick.Model control(MC) group and normal control group were also studied.The scoring system of abdominal withdrawal reflex was used to evaluate visceral pain for behavioral assessment.Enzyme linked immunosorbent assay was performed to determine the concentrations of Dyn and EM in spinal cord.RESULTS:Moxibustion significantly decreased visceral pain to CRD in this rat model,and no significant difference was detected between the SM group and the MC group.In MX group,moxibustion also increased the concentrations of Dyn and EM in spinal cord,and no significant difference was found between the SM group and the MC group.CONCLUSION:Moxibustion therapy can significantly enhance the pain threshold of rats with chronic visceral hyperalgesia,and the effect may be closely related to the increased concentration of Dyn and EM in spinal cord.
文摘Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.
基金Supported by the National Natural Science Foundation of China,No.81503656the National Key Basic Research Program of China(973 Program),No.2015CB554501 and No.2009CB522900
文摘BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1β,IL-18,and resistance-like moleculeβby promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl-aspartate-specific proteinase 1(Caspase-1).The relative DNA abundances of Lactobacillus,Bifidobacteria,Faecalibacterium prausnitzii,and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6,ASC,and Caspase-1 in the colon.CONCLUSION These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling.
文摘Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.GERD symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors involved.Prolonged contact of the esophageal mucosa with the refluxed content,probably caused by a defective anti-reflux barrier and luminal clearance mechanisms,would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium.Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid exposure.Meanwhile,specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD,explaining,in part,the genesis of esophagitis in a subset of patients.Despite these findings,which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD,the relationship between the hypersensitivity and esophageal inflammation is not clear.Moreover,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux disease.This summary aims to explore the inflammatory pathway involved in GERD pathogenesis,to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.
文摘Irritable bowel syndrome(IBS)is common gastrointestinal problems.It is characterized by abdominal pain or discomfort,and is associated with changes in stool frequency and/or consistency.The etiopathogenesis of IBS may be multifactorial,as is the pathophysiology,which is attributed to alterations in gastrointestinal motility,visceral hypersensitivity,intestinal microbiota,gut epithelium and immune function,dysfunction of the brain-gut axis or certain psychosocial factors.Current therapeutic strategies are often unsatisfactory.There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS.Probiotics are living organisms which,when ingested in certain numbers,exert health benefits beyond inherent basic nutrition.Probiotics have numerous positive effects in the gastrointestinal tract.Recently,many studies have suggested that probiotics are effective in the treatment of IBS.The mechanisms of probiotics in IBS are very complex.The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.
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.