抗GQ1b、GT1a、Sulfatide抗体阳性的类重症肌无力Miller-Fisher综合征1例报告

Miller-Fisher综合征(Miller-Fisher syndrome,MFS)是吉兰-巴雷综合征(Guillain-Barre syndrome,GBS)的一种临床变异型,以共济失调、眼肌麻痹及腱反射消失为主要临床特征,极少出现瞳孔改变和瞳孔对光反射异常,一般无症状波动,部分患者可检测到抗GQ1b IgG抗体阳性。本文报告了1例抗GQ1b、GT1a、Sulfatide抗体阳性的MFS,以波动性眼外肌麻痹起病,伴双侧瞳孔散大、对光反射迟钝及四肢麻木无力,症状少见不典型,临床极易误诊。

以球麻痹为主要表现的多项神经节苷脂抗体阳性的Miller-Fisher综合征1例并文献复习

目的 探讨Miller-Fisher综合征(MFS)的诊断学特征。方法 回顾性分析我院诊治的1例以球麻痹为主要表现的多项神经节苷脂抗体阳性的MFS患者的临床资料,对照吉兰-巴雷综合征(GBS)常见类型及临床表现进行分析探讨。结果 GQ1b抗体是MFS患者发病的关键因素,可引起视神经损害和延髓麻痹的症状。结论 MFS患者的临床表现常不典型,GQ1b抗体的沉淀部位与临床表现有相关性,不典型的MFS患者可表现为以球麻痹症状起病。

1例Miller-Fisher综合征合并呼吸衰竭患者的护理

Miller-Fisher综合征(Miller-Fisher syndrome,MFS)是一种罕见的、严重的自限性多发性神经病,病程呈自限性,护理在疾病的全程有着至关重要的作用。本文总结了1例Miller-Fisher综合征合并呼吸衰竭患者的护理经验,护理要点包括在神经重症NCU常规护理的基础上实施评分制的动态量化病情观察、综合心理护理、分阶段联合呼吸功能康复、防治相关并发症。本文分享该疾病的个体化护理经验,以期为提高临床中该类疾病的救治成功率提供参考。

以小脑性共济失调为首发表现的抗ACHR抗体IgG阳性儿童Miller-Fisher综合征1例

Miller-Fisher综合征(Miller-Fisher syndrome,MFS)是吉兰-巴雷综合征(Guillain-Barrésyndrome,GBS)的一种变异型,临床主要表现为共济失调、腱反射减退、眼外肌麻痹[1],而不能以脑脊液有无蛋白-细胞分离现象来排除GBS及MFS的诊断,抗乙酰胆碱受体(acetylcholine receptor,ACHR)抗体IgG阳性也不能认为就是重症肌无力(myasthenia gravis,MG),应依据典型三联神经系统症状,并结合临床综合分析作出临床诊断MFS。

Atypical miller-fisher syndrome after COVID-19 and sleeve gastrectomy:Contribution of neurochemical markers to early diagnosis

Background:The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),began in late 2019.More recently,there have been sporadic case reports on devel-opment of Miller-Fisher Syndrome,a rare variant of Guillain-BarréSyndrome in COVID-19 patients.Case report:We reported herein the case of a French young women presenting with ophtalmoplegia,cerebellar ataxia,and universal areflexia following a bariatric surgery(sleeve gastrectomy).A concomitant COVID-19 diagnosis was retained based on microbiological testing.The patient was successfully treated after high-dose intravenous thiamine,but areflexia persisted.Underlying COVID-19 related Miller-Fisher Syndrome was established on physical examination and confirmed by pathologic neurophysiological findings and elevated level of phosphorylated neurofilament heavy chain protein in cerebrospinal fluid analysis.Conclusions:Guillain-BarréSyndrome and its variants after SARS-CoV-2 infection are extremely rare.The mea-surement of phosphorylated neurofilament heavy chain protein should be considered as an easy tool to detect an early affection of the peripheral nervous system.

椎动脉支架术后Miller-Fisher综合征叠加Bickerstaff脑干脑炎1例

Miller-Fisher综合征(Miller-Fisher syndrome,MFS)和Bickerstaff脑干脑炎(Bickerstaff brainstem encephalitis,BBE)临床较为罕见。近两年,国外可见散在病例报告MFS叠加格林巴利综合征(Guillan-Barrésyndrome,GBS)或BBE,共同影响外周和(或)中枢神经系统,并伴有单相症状。然而,三种疾病叠加的临床症状或体征十分罕见,迄今为止国内未见报道。因此,本研究报告1例64岁男性椎动脉术后亚急性起病,表现为典型的对称性四肢无力、眼外肌麻痹、双下肢腱反射消失,同时伴有嗜睡等意识障碍表现,病程在2周时到达高峰。肌电图检查结果呈神经源性损害,脑脊液和血清学结果提示蛋白-细胞分离现象,GQ1b抗体(anti-GQ1b IgG antibody,GQ1b-IgG)和GT1a抗体(antiGT1a IgG antibody,GT1a-IgG)阳性,临床确诊为MFS叠加BBE。本研究结果强调了MFS、BBE、GBS可能是同一疾病的不同亚型,GQ1b和GT1a抗体进一步揭示了这些疾病亚型的共同免疫相关病理生理机制。临床上,遇到MFS、BBE和GBS叠加、交叉的临床表现,周围和中枢神经系统同时受累时,要考虑到GQ1b抗体综合征可能,尽快给予免疫球蛋白治疗以改善患者预后。

儿童Miller-Fisher综合征和Guillain-Barré综合征的神经电生理对比分析

目的分析儿童Miller-Fisher综合征(Miller-Fisher syndrome,MFS)与Guillain-Barré综合征(Guillain-Barrésyndrome,GBS)的各项神经电生理指标并比较两者的差异,探究两者的神经电生理特征。方法参照2014年多国专家分类组制定的GBS-MFS诊断标准,回顾性收集河南省儿童医院自2013年1月至2020年6月住院确诊为MFS病例33例和GBS病例105例。33例MFS患儿中,男童23例,女童10例,年龄(78.15±43.22)个月;105例GBS患儿中,男童69例,女童36例,年龄(64.73±33.90)个月。收集整理入选患者的神经电生理资料,采用t检验、秩和检验、χ^(2)检验对数据进行统计分析。结果33例MFS患儿中,H反射异常19例(57.6%),感觉神经传导异常14例(42.4%),正常神经电生理9例(27.3%);105例GBS患儿中,运动神经传导异常98例(93.3%),H反射异常92例(87.6%),感觉神经传导异常62例(59.0%),针电极肌电图异常44例(41.9%)。感觉神经异常指标中,MFS患儿感觉神经动作电位(SNAP)波幅降低(33.3%,11/33)发生率最高,GBS患儿SNAP未引出(36.2%,38/105)发生率最高。GBS患儿较MFS患儿SNAP波幅降低、感觉神经传导速度(SCV)减慢(均P<0.05)。结论MFS患儿神经电生理异常主要为H反射异常和感觉神经异常,感觉异常指标以SNAP波幅降低最常见,GBS患儿则表现为运动和感觉神经均异常,且以运动神经异常最显著。MFS与GBS神经电生理有明显差异,认识这些差异可以为MFS、GBS的早期诊断及鉴别诊断提供更多的参考依据。

类似眼肌型重症肌无力的Miller-Fisher综合征1例

Miller-Fisher综合征是吉兰-巴雷综合征(Guillain-Barre syndrome,GBS)的变异型之一,典型表现为共济失调、眼外肌麻痹和腱反射消失,且多数患者血清中可检测到抗神经节苷脂Q1b(ganglioside Q1b,GQ1b)抗体。本文报道1例症状与眼肌型重症肌无力表现相似的Miller-Fisher综合征患者。

Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.

Tricuspid mass-curious case of Li-Fraumeni syndrome: A case report

BACKGROUND Li-Fraumeni syndrome(LFS)is a rare autosomal dominant cancer-predisposing syndrome,which can manifest as a polymorphic spectrum of malignancies.LFS is associated with an early onset in life,with the majority of cases occurring prior to the age of 46.Notwithstanding the infrequency of primary cardiac tumors,it behooves clinicians to remain vigilant in considering the differential diagnosis of such tumors in LFS patients who present with a cardiac mass.This is due to the markedly elevated risk for malignancy in this particular population,far surpassing that of the general populace.CASE SUMMARY Herein,we present a case of a 30-year-old female with LFS who was found to have a tricuspid valve leaflet mass.CONCLUSION This case exemplifies valuable learning points in the diagnostic approach for this exceptionally rare patient population.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Body composition and metabolic syndrome in patients with type 1 diabetes

BACKGROUND In recent years,the prevalence of obesity and metabolic syndrome in type 1 diabetes(T1DM)patients has gradually increased.Insulin resistance in T1DM deserves attention.It is necessary to clarify the relationship between body composition,metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention.AIM To assess body composition(BC)in T1DM patients and evaluate the relationship between BC,metabolic syndrome(MS),and insulin resistance in these indi-viduals.METHODS A total of 101 subjects with T1DM,aged 10 years or older,and with a disease duration of over 1 year were included.Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters.Clinical and laboratory data were collected,and insulin resistance was calculated using the estimated glucose disposal rate(eGDR).RESULTS MS was diagnosed in 16/101 patients(15.84%),overweight in 16/101 patients(15.84%),obesity in 4/101(3.96%),hypertension in 34/101(33.66%%)and dyslip-idemia in 16/101 patients(15.84%).Visceral fat index(VFI)and trunk fat mass were significantly and negatively correlated with eGDR(both P<0.001).Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients.Binary logistic regression analysis revealed that significant factors for MS included eGDR[P=0.017,odds ratio(OR)=0.109],VFI(P=0.030,OR=3.529),and a family history of diabetes(P=0.004,OR=0.228).Significant factors for hypertension included eGDR(P<0.001,OR=0.488)and skeletal muscle mass(P=0.003,OR=1.111).Significant factors for dyslipidemia included trunk fat mass(P=0.033,OR=1.202)and eGDR(P=0.037,OR=0.708).CONCLUSION Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM.BC analysis,specifically identifying visceral fat(trunk fat),may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Incidence and risk factors of depression in patients with metabolic syndrome

BACKGROUND Many studies have explored the relationship between depression and metabolic syndrome(MetS),especially in older people.China has entered an aging society.However,there are still few studies on the elderly in Chinese communities.AIM To investigate the incidence and risk factors of depression in MetS patients in China's Mainland and to construct a predictive model.METHODS Data from four waves of the China Health and Retirement Longitudinal Study were selected,and middle-aged and elderly patients with MetS(n=2533)were included based on the first wave.According to the center for epidemiological survey-depression scale(CESD),participants with MetS were divided into depression(n=938)and non-depression groups(n=1595),and factors related to depression were screened out.Subsequently,the 2-,4-,and 7-year follow-up data were analyzed,and a prediction model for depression in MetS patients was constructed.RESULTS The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%.The prevalence of depression at the 2-,4-,and 7-year follow-up was 29.55%,34.53%,and 38.15%,respectively.The prediction model,constructed using baseline CESD and Physical Self-Maintenance Scale scores,average sleep duration,number of chronic diseases,age,and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up(area under the curve=0.775,95%confidence interval:0.750-0.800,P<0.001),with a sensitivity of 68%and a specificity of 74%.CONCLUSION The prevalence of depression in middle-aged and elderly patients with MetS has increased over time.The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.

Immune cell signatures and causal association with irritable bowel syndrome:A mendelian randomization study

BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.

Causal role of immune cells in obstructive sleep apnea hypopnea syndrome:Mendelian randomization study

BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to OSAHS.Using a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.AIM To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical research.METHODS A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS.Summary statistics for each immune cell feature were obtained from the GWAS catalog.Information on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic databases.The results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity examination.RESULTS Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was observed.However,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.

Metabolic syndrome’s new therapy:Supplement the gut microbiome

This letter to the editor discusses the publication on gut microbiome supple-mentation as therapy for metabolic syndrome.Gut microbiome dysbiosis disrupts intestinal bacterial homeostasis and is related to chronic inflammation,insulin resistance,cardiovascular diseases,type 2 diabetes mellitus,and obesity.Previous research has found that increasing the abundance of beneficial microbiota in the gut modulates metabolic syndrome by reducing chronic inflammation and insulin resistance.Prebiotics,probiotics,synbiotics,and postbiotics are often used as supplements to increase the number of beneficial microbes and thus the produc-tion of short-chain fatty acids,which have positive effects on the gut microbiome and metabolic syndrome.In this review article,the author summarizes the available supplements to increase the abundance of beneficial gut microbiota and reduce the abundance of harmful microbiota in patients with metabolic disorders.Our group is also researching the role of the gut microbiota in chronic liver disease.This article will be of great help to our research.At the end of the letter,the mechanism of the gut microbiota in chronic liver disease is discussed.

Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.