Ischemic white matter damage is a significant pathological feature of chronic cerebral hypoperfusion, leading to cognitive impairments. However, the underlying molecular mechanisms remain poorly understood. In this study, we identify a causal association between genetically predicted extracellular signal-regulated kinase 5 (ERK5) expression and higher white matter hyperintensity volume through druggable target screening, suggesting its potential as a therapeutic target for white matter damage. Using different animal models of white matter damage, we show that Erk5 expression is significantly upregulated in microglia following both ischemic and demyelinating injury, correlating with the severity of white matter damage. Mechanistically, Erk5 exacerbates white matter damage by promoting microglial ferroptosis through the phosphorylation of nuclear factor of activated T-cells, cytoplasmic 4 (Nfatc4), which subsequently activates the expression of cleft lip and palate transmembrane protein 1-like protein (Clptm1l), a lipid scramblase involved in ferroptosis. Pharmacological and genetic inhibition of Erk5 in microglia effectively mitigates oxidative stress, lipid peroxidation, and ferroptosis, leading to a reduction in white matter damage and improved cognitive function. These findings underscore the potential of targeting the Erk5-Nfatc4-Clptm1l axis as a therapeutic strategy for ischemic white matter damage. Our study offers valuable insights into the molecular pathways driving white matter damage and provides a framework for the clinical translation of Erk5 inhibitors in the treatment of ischemic white matter damage.

Background:Glycogen storage disease type IX α2 (GSD IX α2) is an X-linked hepatic glycogenosis caused by pathogenic variants in PHKA2. Noncanonical splice-region variants located outside the invariant GT/AG dinucleotides pose significant interpretive challenges, as in silico predictions alone are often insufficient for definitive classification. Case Description:We report a 2.9-year-old boy presenting with short stature, hepatomegaly, markedly elevated aminotransferases, fasting hypoglycemia with ketonuria, hypercholesterolemia, coagulation parameter abnormalities (decreased fibrinogen and prolonged thrombin time), and histological evidence of early hepatic fibrosis as demonstrated by Masson's trichrome staining (portal fibrosis and perisinusoidal fibrosis). Whole-exome sequencing (WES) identified a hemizygous, previously unreported PHKA2 variant [NM_000292.3:c.2517+5G>T, genomic location (GRCh38): NC_000023.11: g.18907895G>T], initially classified as a variant of uncertain significance (VUS) under American College of Medical Genetics and Genomics (ACMG) criteria. RNA sequencing of peripheral blood leukocytes demonstrated predominant exon 22 skipping in 94.2% of informative junction reads, predicting a frameshift and premature termination codon [p.(Gly788Profs*74)] with predicted loss of the C-terminal CBL 2 subdomain. Incorporating this transcript-level evidence, the variant was reclassified as pathogenic (PVS1 + PM2_Supporting + PP4). Following dietary management with uncooked cornstarch supplementation, the patient showed progressive biochemical improvement over a 2.2-year follow-up. Conclusions:This case expands the mutational spectrum of PHKA2 and demonstrates that RNA sequencing of accessible tissues is a practical and diagnostically informative strategy for resolving noncanonical splice-region variants in pediatric hepatic GSD. Early hepatic fibrosis detected by histological examination before age 3 years underscores the importance of longitudinal hepatic surveillance in GSD IX α2.

IntroductionInflammatory bowel disease (IBD) is a complex immune-mediated condition, and biologics are the most commonly used drugs for its treatment. However, there are still cases of ineffective treatment. B-cell lymphoma 6 (Bcl6), a transcriptional suppressor, is known to have regulatory effects on multiple immune-associated cell subsets. FX1, a novel specific BCL6 Bric-à-brac (BTB) inhibitor, has shown positive effects in many disease models, but its effects and mechanisms in IBD control remain unclear.MethodsWe observed colon length and DAI score of colitis mice after treatment. HE staining section was used to evaluate colonic injury, while the expression of colonic pro-inflammatory cytokines by RT-qPCR. And differences in immune cell subsets between the two groups was analyzed by flow cytometry. Additionally, IHC and RT-qPCR were employed to evaluate the expression of colonic tight junction proteins. Furthermore, RAW264.7 cells and co-cultured Caco2 cells were detected by ELISA and RT-qPCR.ResultsIn the treat group, colitis symptoms in mice were significantly improved, and there was a decrease in proportion of macrophages and protection of intestinal mucosal integrity-indicating anti-inflammatory effects of FX1. In cell experiments, we found that FX1 decreased secretion of pro-inflammatory factors by macrophages and increased expression of tight junction proteins in Caco2 cells after co-culture.DiscussionThe experimental findings demonstrate the inhibitory effect of FX1 on inflammation in murine colitis model as well as its potential mechanism. BCL6 is a potential target for treating IBD.

Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn’s disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD. In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80

BACKGROUND AND AIMS:Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis. APPROACH AND RESULTS:Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model. CONCLUSIONS:Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.

N6-methyladenosine (m6A) is the most abundant modification of eukaryotic mRNA and is involved in almost every stage of RNA metabolism. The m6A modification on RNA has been demonstrated to be a regulator of the occurrence and development of a substantial number of diseases, especially cancers. Increasing evidence has shown that metabolic reprogramming is a hallmark of cancer and is crucial for maintaining the homeostasis of malignant tumors. Cancer cells rely on altered metabolic pathways to support their growth, proliferation, invasion and metastasis in an extreme microenvironment. m6A regulates metabolic pathways mainly by either directly acting on metabolic enzymes and transporters or indirectly influencing metabolism-related molecules. This review discusses the functions of the m6A modification on RNAs, its role in cancer cell metabolic pathways, the possible underlying mechanisms of its effects and the implication of this modification in cancer therapy.

Background Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn’s disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children. Methods We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy. Results Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029). Conclusion This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.

目的 探讨儿童肝硬化的病因及临床特征,了解其预后,提高对其认识和诊治水平.方法 回顾性分析华中科技大学同济医学院附属同济医院儿童消化专科2016年10月至2020年12月收治的36例儿童肝硬化患儿的临床资料,包括性别、年龄、既往史、病因、临床表现、并发症、确诊时营养状况、实验室检查结果、基因结果和治疗后随访情况等,比较预后良好组与死亡组患儿的相关指标差异.结果 36例肝硬化患儿,男18例,女18例,年龄为51.7(5,84)月,其中胆道闭锁13例,肝豆状核变性6例,先天性肝内胆管扩张症(Caroli病)2例,进行性家族性肝内胆汁淤积症(PFIC)2例,遗传性出血性毛细血管扩张症(HHT)1例,尼曼-匹克病1例,先天性胆汁酸合成障碍1例,新生儿肝内胆内淤积症(NICCD)1例、SDS综合征1例,乙肝肝硬化1例,隐源性肝硬化7例.临床特征主要为脾大18例(50％)、皮肤黄染16例(44.4％)、发热10例(27.7％)、腹胀10例(27.7％)、消化道出血6例(16.6％)、呕吐4例(11.1％)等.确诊肝硬化时8例(22.2％)患儿存在体重低下,12例(33.3％)患儿存在生长迟缓.36例全部行肝胆B超检查诊断肝硬化,其中14例腹部CT检查诊断肝硬化,15例组织病理诊断肝硬化.并发症主要包括食管胃底静脉曲张9例(26.4％),脾功能亢进和(或)血细胞减少8例(23.5％),腹腔积液6例(16.6％)等.10例完善基因相关检查,6例检测出致病基因,分别为NPC1、ABCB4、SADM4、ATP7B、SBDS和SLC25A13;所有患儿优先根据病因治疗,在此基础上加用护肝和退黄药等对症支持治疗,其中27(75％)例患儿一般情况良好,7(19.4％)例死亡,8例患儿已行肝移植治疗,2例患儿目前等待肝移植.预后良好组与死亡组两组比较,在丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、凝血酶原时间(PT)、血小板、总胆红素(TBIL)方面差异无统计学意义(P均＞0.05);在患儿确诊时年龄、白蛋白(ALB)、直接胆红素(DBIL)方面差异有统计学意义(P＜0.05).结论 儿童肝硬化的病因与成人大不相同,胆道闭锁是其最常见的病因;B超是诊断其最常用的检查方法;肝硬化患儿易出现营养不良,建议加强营养补充;患儿起病年龄越小,伴白蛋白水平越低、直接胆红素水平越高时其预后差、病死率高.

目的 研究淫羊藿苷对激素性股骨头坏死的保护作用及机制.方法 分离SD大鼠骨髓间充质干细胞(rBMSCs)并按以下方式干预:对照组、地塞米松组(1×10-6 mol/L),联合干预组[地塞米松(1×10-6 mol/L)+不同浓度淫羊藿苷(1×10-8 mol/L,1×10-7 mol/L,1×10-6 mol/L,1×10-5 mol/L)];检测各组细胞增殖、凋亡、成骨/成脂分化情况,以及转录共激活因子(transcriptional co-activator with PDZ-binding mo-tif,TAZ)、结缔组织生长因子(connective tissue growth factor,CTGF)、Runt相关转录因子2(Runt-related transcriptional factor 2,Runx2)蛋白表达变化;siRNA沉默TAZ后,观察各组下游CTGF、Runx2表达变化.体内实验使用52只SD大鼠,随机分为对照组、甲强龙组(甲基强的松龙40 mg·kg-1·d-1)和联合干预组(甲基强的松龙40 mg·kg-1·d-1+淫羊藿苷100 mg·kg-1·d-1).HE染色评估股骨头骨小梁结构;免疫组化染色评估抗骨钙蛋白(osteocalcin,OCN)、TAZ、血小板-内皮细胞粘附分子(Platelet endothelial cell adhesion molecule-1,PECAM-1/CD31)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达;TUNEL染色评估细胞凋亡情况;Micro-CT评估股骨头骨密度、骨体积/总体积、骨小梁数、骨小梁间距和骨小梁厚度;血管造影评估股骨头血供情况.结果 体外实验表明地塞米松能促进rBMSCs凋亡和成脂分化,抑制其增殖和成骨分化;而淫羊藿苷能显著削弱这些效应.此外,淫羊藿苷能显著逆转地塞米松对rBM-SCs中TAZ、CTGF蛋白表达的影响.抑制TAZ表达后,联合干预组rBMSCs中Runx2的表达也受到抑制.体内实验结果证实淫羊藿苷可保护大鼠股骨头软骨下骨质和股骨头内血液供应免受激素的破坏.激素能显著抑制大鼠股骨头TAZ表达,而淫羊藿苷能促进TAZ表达.结论 淫羊藿苷可通过激活TAZ表达来预防大鼠激素性股骨头坏死的发生发展.

Background:Fecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children. Methods:Retrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses. Results:A total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation. Conclusions:FMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.

Pre-operative exercise therapy improves outcomes for many patients who undergo surgery. Despite the well-known effects on tolerance to systemic perturbation, the mechanisms by which pre-operative exercise protects the organ that is operated on from inflammatory injury are unclear. Here, we show that four-week aerobic pre-operative exercise significantly attenuates liver injury and inflammation from ischaemia and reperfusion in mice. Remarkably, these beneficial effects last for seven more days after completing pre-operative exercising. We find that exercise specifically drives Kupffer cells toward an anti-inflammatory phenotype with trained immunity via metabolic reprogramming. Mechanistically, exercise-induced HMGB1 release enhances itaconate metabolism in the tricarboxylic acid cycle that impacts Kupffer cells in an NRF2-dependent manner. Therefore, these metabolites and cellular/molecular targets can be investigated as potential exercise-mimicking pharmaceutical candidates to protect against liver injury during surgery. Zhang et al. show that pre-operative exercise protects against liver injury by driving Kupffer cells towards an anti-inflammatory phenotype via itaconate metabolism.

Abstract Surgical removal of malignant tumors is a mainstay in controlling most solid cancers. However, surgical insult also increases the risk of tumor recurrence and metastasis. Tissue trauma activates the innate immune system locally and systemically, mounting an inflammatory response. Platelets and neutrophils are two crucial players in the early innate immune response that heals tissues, but their actions may also contribute to cancer cell dissemination and distant metastasis. Here we report that surgical stress–activated platelets enhance the formation of platelet-tumor cell aggregates, facilitating their entrapment by neutrophil extracellular traps (NET) and subsequent distant metastasis. A murine hepatic ischemia/reperfusion (I/R) injury model of localized surgical stress showed that I/R promotes capturing of aggregated circulating tumor cells (CTC) by NETs and eventual metastasis to the lungs, which are abrogated when platelets are depleted. Hepatic I/R also increased deposition of NETs within the lung microvasculature, but depletion of platelets had no effect. TLR4 was essential for platelet activation and platelet-tumor cell aggregate formation in an ERK5-GPIIb/IIIa integrin-dependent manner. Such aggregation facilitated NET-mediated capture of CTCs in vitro under static and dynamic conditions. Blocking platelet activation or knocking out TLR4 protected mice from hepatic I/R-induced metastasis with no CTC entrapment by NETs. These results uncover a novel mechanism where platelets and neutrophils contribute to metastasis in the setting of acute inflammation. Targeted disruption of the interaction between platelets and NETs holds therapeutic promise to prevent postoperative distant metastasis. Significance: Targeting platelet activation via TLR4/ERK5/integrin GPIIb/IIIa signaling shows potential for preventing NET-driven distant metastasis in patients post-resection.

Liver metastasis is the main cause of colorectal cancer (CRC)-related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long-term daily administrations of recombinant DNase I, we have developed an adeno-associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV-mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV-DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV-DNase I and AAV-null treatments. Our data suggest that AAV-mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.

e16002 Background: Immune checkpoint inhibitors (ICIs) are currently approved for microsatellite instability-high metastatic colorectal cancer (mCRC) however reported objective response rate to monotherapy range between 28-52%. Neutrophil Extracellular Traps (NETs), an extracellular network of DNA and proteins expelled by neutrophils into the tumor microenvironment, promote CRC metastasis by inducing potent immunosuppressive effects. We hypothesize that targeting this network may improve response rates to immune checkpoint therapy. The purpose of our study is to investigate the effect of combination DNase I treatment, a NET depleting agent, and PD-1 blockade in mCRC progression. Methods: Subcutaneous MC38 (MSI-H adenocarcinoma of the colon) tumors were established in 6-week-old mice. Treatment was initiated six days after tumor inoculation with daily intraperitoneal (i.p) injections of DNase I followed by i.p anti-PD-1 treatment administered every 3 days. Animals were divided into treatment groups: control, DNase alone, anti-PD-1 alone and combination of DNase I with anti-PD-1 (n = 6 mice/ group). Results: Tumors were successfully established after 6 days of inoculation. These tumors expressed high neutrophil infiltration and NETs. To determine the effects of combination therapy on tumor progression, we measured tumor volume and time to progression (TTP). We found that mice treated with combination DNase I and anti-PD-1 had significantly lower mean tumor volume compared to anti-PD-1 alone (1372.68mm3 vs 2193.20 mm3, p-value = 0.043). TTP was higher in the combination group compared to anti-PD-1 treatment alone (median time to progression 22 vs 17 days, p-value = 0.004). Next we sought to determine the mechanism behind this effect by investigating if NETs blockade modulated the tumor microenvironment. We found that treatment with DNase I decreased exhaustion of CD8+ T-cells in the tumor compared to no treatment. Conclusions: Targeting NETs in combination with immune checkpoint inhibition may be an option to improve response rate to immune checkpoint inhibitors through decreasing exhausted CD8+ T-cells.

Citrin deficiency initially presents as neonatal intrahepatic cholestasis (NICCD) and often resolves within first year of infancy. Failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) has been recently proposed as a novel post-NICCD phenotype and its clinical features are still being established. Herein, we encountered a 2-year-old girl who was hospitalized for intermittent fever lasting 10 days. Besides pneumonia, we observed an NICCD-like phenotype with the presence of liver dysfunction, dyslipidemia, aminoacidemia, organic academia, and extremely high levels of alpha-fetoprotein (AFP). Genetic testing confirmed the diagnosis of citrin deficiency and, liver histology revealed she had already developed cirrhosis. Although, improvement of biochemical parameters and liver histology were observed after treatment that included dietary restrictions and symptomatic treatments, AFP levels remained elevated (>400 ng/ml) during a 3-year follow-up period. Moreover, liver magnetic resonance imaging (MRI) examination performed on the patient at age 5 revealed the development of multiple liver nodules with diffusion restriction on diffusion-weighted imaging (DWI). These observations highly indicate the possibility of hepatocellular carcinoma (HCC). Thus, this case reveals that an NICCD-like phenotype complicated with cirrhosis can exist during FTTDCD stage without any prior signs. It also emphasizes the necessity of monitoring AFP levels during follow-up for citrin deficiency patients with persistently high AFP level after treatment as FTTDCD may progress to HCC. Individualized treatment strategy for patients with FTTDCD also need to be explored.

目的 探讨肺炎支原体(MP)感染并发重症渗出性多形性红斑(SJS)的特点,指导合理用药.方法 回顾1例MP肺炎应用多种头孢菌素出现SJS的诊治经过,分析SJS的发生原因,总结其中的经验和教训.结果 该患儿出现SJS为MP感染和不合理使用抗菌药物的综合因素导致,高敏体质是出现该严重并发症的基础.结论 MP感染可累及肺部以外的器官,当出现皮肤黏膜受累迹象时,应避免β-内酰胺类抗菌药物等高危药物的使用,警惕SJS等严重并发症,并对其进行早期识别、及时诊断和正确治疗.

目的 观察粪菌移植对儿童难治性功能性便秘的临床疗效并探讨其机制.方法 对4例临床确诊为难治性功能性便秘患儿给予粪菌移植治疗,观察和记录患儿临床症状改善情况并收集供体和粪菌移植治疗前后患儿粪便标本,利用Illumina MiSeq测序平台进行16S rRNA测序,并对测序结果进行生物信息学分析.结果 4例患儿接受粪菌移植治疗后排便状况明显改善,大便次数增加、粪便硬度变软、腹部胀痛明显缓解.粪菌移植后,息儿肠道菌群多样性下降,患儿与供体的肠道菌群差异先增大后逐渐缩小.菌群分析显示患儿肠道有害菌受到抑制、有益菌增加.结论 粪菌移植可有效改善儿童难治性功能性便秘的临床症状,具有疗程短、治疗方便、无明显不良反应等优点.

AIM:To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM).METHODS:We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis.RESULTS:After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically.CONCLUSION:FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of intestine,the pathogeny of which still remains unknown.There are more and more evidences showing that the imbalance of intestinal flora may be involved in the occurrence and development of IBD.Fecal microbiota transplant (FMT) is the process of transplanting fecal bacteria from a healthy individual into a recipient.It aims to restore the normal colonic microflora and treat the disease.The maintenance of intestinal and microbial homeostasis is increasingly recognized as playing a pivotal role in overall health,and the dysregulation of either gut or microbial homeostasis may play a role in many diseases,including inflammatory bowel disease (IBD).There has been a growing interest in the use of FMT as a treatment of IBD.This paper mainly reviewed the application of FMT in the treatment of children with IBD.