Enterohepatic circulation is essential for maintaining a constant bile acid concentration. Diseases with enterohepatic circulation disturbances are usually difficult to diagnose definitively without the time-consuming and expensive genetic tests. This study analyzed and compared duodenal fluid in patients with biliary atresia (BA), familial intrahepatic cholestasis 2 (FIC2), and sodium taurocholate cotransporting polypeptide (NTCP) deficiency. This study aimed to assess the diagnostic value of duodenal fluid analysis in patients with enterohepatic circulation disturbance. This study retrospectively analyzed data from 18 patients with BA, 13 patients with FIC2, and 15 patients with NTCP deficiency. All patients completed the duodenal tube tests before receiving treatment for cholestasis. The patients were intubated through the right nasal cavity to the middle or lower duodenum, as confirmed by radiography. 3-5 mL of duodenal fluid was collected at last. Clinical presentations, laboratory data, genetic data, and so forth were collected for the analysis. Among the 3 types of diseases, levels of total bile acid (TBA), total bilirubin (TB), direct bilirubin (DB), and gamma-glutamyl transpeptidase (GGT) in duodenal fluid showed significant differences (P < .01). Compared with the same indications in duodenal fluid, levels of TBA and GGT in serum did not show significant differences between patients with FIC2 and NTCP deficiency (P > .05). Duodenal TBA/serum TBA ratio, duodenal TB/serum TB ratio, duodenal DB/serum DB ratio, and duodenal GGT/serum GGT ratio also showed significant differences between patients with BA and NTCP deficiency, between patients with FIC2 and NTCP deficiency (P < .01). For diagnosis of BA, increased GGT and absent TB, DB, and TBAs had a sensitivity of 100%, 100%, 100%, and 100%, a specificity of 86.1%, 100%, 97.2%, and 97.2%. Duodenal tube tests have been used for the diagnosis of BA for over 10 years. Our findings support the duodenal fluid analysis as a tool for prompt timely diagnosis of BA. This study also indicates that the test is a useful diagnostic method with high accuracy for other diseases with enterohepatic circulation disturbance.

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

BackgroundChildren with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance.MethodsAll children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups.ResultsA total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05).ConclusionPositive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

BackgroundThis investigation aimed to examine the epidemiological characteristics of children with liver disease hospitalized for the first time between June 2012 and May 2022 in a tertiary hospital.MethodsThe study retrospectively recruited children aged between 29 days and 18 years who had been hospitalized for liver disease. Clinical characteristics were categorized by age and etiology, and time trends were assessed using linear regression analysis.ResultsA total of 4,313 children were recruited, with a median age of 0.7 (0.2–4.5) years, and 54.5% of the cases were in the 0–1 years age group. Infection was the primary cause of liver disease (30.0%), followed by undiagnosed cases (25.8%), biliary obstructive disease (15.9%), inherited metabolic liver disease (13.9%), and non-alcoholic fatty liver disease (NAFLD) (3.2%). Genetic diagnoses were established in 43.9% (478/1,088) of patients. The percentage of NAFLD demonstrated an upward trend from 1.2% in 2012 to 12.6% in 2022 (p = 0.006). In contrast, the percentage of cytomegalovirus hepatitis decreased from 13.3% in 2012 to 3.4% in 2022 (p = 0.002).ConclusionsLiver disease in infancy makes up the largest group in pediatric liver disease. Infection remains the leading cause of pediatric liver disease. Hospital admissions for NAFLD in children have increased rapidly over the past decade, while cytomegalovirus hepatitis has declined markedly.

BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a common clinical phenotype of citrin deficiency in infants. Its phenotype is atypical, so genetic testing is quite necessary for the diagnosis.Case presentationWe report 4 patients with jaundice and low body weight. Furthermore, the biochemical examination of all showed abnormal liver function and metabolic changes. DNA samples of the patients were extracted and subjected to genetic screening. All candidate pathogenic variants were validated by Sanger sequencing, and CNVs were ascertained by qPCR. The genetic screening revealed 6 variants in 4 patients, and all patients carried compound heterozygous variants of SLC25A13. Importantly, 3 variants were newly discovered: a nonsense mutation in exon17 (c.1803C > G), a frameshift mutation in exon 11(c.1141delG) and a deletion of the whole exon11. Thus, four NICCD patients were clearly caused by variants of SLC25A13. Biochemical indicators of all patients gradually returned to normal after dietary adjustment.ConclusionsOur study clarified the genetic etiology of the four infants, expanded the variant spectrum of SLC25A13, and provided a basis for genetic counseling of the family. Early diagnosis and intervention should be given to patients with NICCD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient's symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms.

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.

Abstract Background Wilson disease (WD) is an autosomal-recessive metabolic disorder characterized by excess copper accumulation predominantly in the liver, brain, and cornea. Clinical diagnosis of WD remains a challenge because of its phenotypic heterogeneity. Here we describe the novel mutation (p. K838N) in the ATP7B gene of a child with WD. The mutation affects a conserved ATP-binding domain that is involved in the catalytic cycle. We also describe the clinical outcome of this patient. Case presentation: We reported a successful early diagnosis and treatment of WD in a 5-year-old boy who presented with unexplained liver dysfunction and hepatitis. Using whole-exome sequencing (WES), we identified a novel ATP7B mutation, K838N, which is valuable for early diagnosis of WD. After combination therapy with penicillamine, zinc supplement, low-copper diet, and supportive treatments for infections, liver problems, and jaundice, the patient’s medical condition gradually improved and stabilized in a clinical follow-up. We suggested that the novel K838N mutation in the case of WD might impair protein function and contribute to WD progression. Conclusions This case emphasizes the importance of WD diagnostic tests during clinical evaluation for patients presenting with an unexplained liver disorder in childhood for better outcomes and genetic counseling.

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 探讨由基因或结构异常所致慢性胰腺炎患儿的临床特点,及其经内镜逆行胰胆管造影术(ERCP)诊治的临床疗效.方法 回顾分析2020年7-10月采用ERCP治疗的3例慢性胰腺炎患儿的临床资料.结果 3例慢性胰腺炎患儿,2例男性、1例女性,年龄为11岁1例,12岁2例,主要临床症状均为慢性腹痛,无胰腺内外分泌功能不全的表现.2例患儿由基因变异所致,分别为SPINK 1、LPL基因变异;1例由结构异常所致,为胰管先天发育异常,胰体部胰管呈分支状.3例患儿常规治疗无效,实施ERCP治疗,通过取出结石、清理胰管、放置支架,以改善引流,缓解胰管压力.术后2例患儿的胰酶均恢复正常,腹痛缓解;1例术后胰酶增高,3天后恢复正常.结论 由基因或结构异常所致儿童慢性胰腺炎行ERCP诊治安全有效.

Clinical data of a case of Munchausen syndrome by proxy (MSBP) admitted to the Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in November 2020 were retrospectively analyzed.The 4 years and 4 months old female patient presented with retrosternal and abdominal pain for 1 month, and aggravated with multi-organ pain for 20 days.She complained about the retrosternal pain with acid reflux, pain in the teeth, esophagus, and abdomen, etc.During the hospitalization, she frequently complained of multi-organ pain.Her mother repeatedly declared her painful hip joint and she often cried for pain at night, and even could not walk.However, the clinical examination showed no obvious abnormalities.Combining characteristics of the patient and her caregiver, the patient was confirmed as MSBP.It is suggested that MSBP in children should be concerned in cases with complicated severe chief complaints, frequent medical visits, and a strong willing to see a doctor or be hospitalized by their caregivers, but normal physical and auxiliary examination findings.

Niemann–Pick disease is a relatively common lysosomal storage disease. Cholestatic liver disease is a typical clinical phenotype of Niemann–Pick disease in infancy. The diagnosis is traditionally based on Niemann–Pick cells in bone marrow smears or liver biopsies. Treatment for cholestatic liver disease mainly includes ursodeoxycholic acid and liver protection drugs. Here, we reported two cases of Niemann–Pick disease type C, diagnosed by genetic analysis during early infancy. Besides cholestatic jaundice, the two patients also exhibited signs of immune system hyperactivity, such as elevated immunoglobulins or multiple autoantibodies, which might require the application of glucocorticoids. In addition, three novel missense variants of the NPC1 gene were identified. The findings suggest that immune activation should be considered as a “new” clinical phenotype of lysosomal storage diseases.

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.

《医学微生物学》对于医学生在单一病原微生物的分离培养鉴定、临床诊断方面学习培训起到重要作用.社会及医学科技的发展使得感染谱发生了变化,宏观生态破坏导致的跨物种新突发传染病不时出现,与此同时,正常菌群成员成了人体感染的主要原因菌,且多呈现出高度耐药的形式.一维地应用抗生素不能解决这些问题,这需要用微生态的理论来思考感染的起因与防治.迫切需要将微生态学内容融入医学生的医学微生物学的基础教育之中,以加强和拓展医学生对微生物的视角,因此建议将《医学微生物学》更名为《医学微生物与微生态学》.

2019年12月以来,湖北武汉市发现新型冠状病毒肺炎患者.随着疫情的蔓延,我国其他地区及境外也相继发现此类病例,引起了我国和世界各国的高度关注.世界卫生组织命名为COVID-19(新型冠状病毒肺炎).新型冠状病毒主要经呼吸道飞沫和密切接触传播,人群普遍易感,严重危害人民生命健康.为此,我国作为急性呼吸道传染病并纳入《中华人民共和国传染病防治法》规定的乙类传染病,按甲类传染病管理.近日,国家卫生健康委员会与国家中医药管理局发布了《新型冠状病毒肺炎诊疗方案(试行第六版)》在治疗中强调避免盲目或不恰当使用抗菌药物,尤其是联合使用广谱抗菌药物.推荐使用肠道微生态调节剂,维持肠道微生态平衡,预防继发性细菌感染,有助于提高治愈率,降低死亡率.

粪菌移植是一种直接改变受体肠道微生物群以使其正常化,从而获得治疗效益的方法.自2013年美国食品和药物管理局批准粪菌移植用于治疗复发性和难治性艰难梭菌感染以来,粪菌移植成为研究热点.从此,粪菌移植应用的范围迅速扩大,不仅用于胃肠道疾病,而且用于胃肠外疾病.虽然目前的证据认为粪菌移植是一种普遍安全、副作用少的治疗方法,但其扩大适应症及安全性问题尚未形成共识,需要更深入的研究.本文就目前粪菌移植与胃肠内外疾病的关系及临床安全性问题进行综述,为临床更好地开展粪菌移植提供参考.

Bilirubin is an important endogenous substance in human body, which can be divided into conjugated bilirubin and unconjugated bilirubin.Learning the production and transportation of bilirubin, the different types of bilirubin and their biological characteristics, the excretion and reabsorption of bilirubin and other metabolic processes will help us understand the pathogenesis and mechanisms of a series of clinical diseases with jaudice, which facilitate the diagnosis and treatment of related diseases.

人类肠道是一个生态系统,存在大量的微生物,肠道微生态即为肠道微生物群与其宿主之间相互作用、相互影响的统一体[1].肠道微生物由细菌、病毒、真菌等构成,其中主要为细菌,肠道菌群作为肠道微生态的重要组成部分,对宿主健康有极大的影响[2-3].大量研究显示,肠道菌群的生理功能主要包括,生物拮抗(防御感染)、参与营养吸收及代谢、参与免疫系统成熟和调节免疫应答等[ 3 ].在生命早期1000天建立健康的肠道菌群,对肠道黏膜免疫系统和全身免疫系统的发育和成熟具有重要作用,尤其是婴幼儿期[3].母亲孕期、分娩时及出生后多种因素影响婴幼儿肠道菌群的定植及构成.益生菌、益生元、共生元等,具有维持或调整微生态平衡、防治疾病和增进宿主健康的作用,因而日益受到关注.本文综述肠道微生态与婴幼儿免疫的关系.

进行性家族性肝内胆汁淤积症(progressive familial intrahepatic cholestasis,PFIC)是一组常染色体隐性遗传性胆汁淤积性肝病,1969年由国外学者首次提出[1],常于新生儿期或1岁以内起病,由于不同类型基因突变导致胆汁酸转运缺陷,进而引起胆汁淤积和肝细胞损伤.主要表现为严重肝内胆汁淤积,可反复发生或者持续进展,最终进展为肝衰竭[2].该病发病率为1∶100000至1∶50000,男女发病率差异无统计学意义[3].最新研究表明,目前已发现6种不同类型的基因缺陷导致PFIC,包括FIC1、ATP8B1、ABCB11、TJP2、NR1H4和MYO5B[4-6].本文总结了PFIC不同疾病谱的临床特点和发病机制,并简要概述了相关治疗方案.

艰难梭菌感染(Clostridium difficile infection,CDI)是院内抗生素相关性腹泻的最重要因素之一,其主要临床表现包括血便、腹泻、中毒性巨结肠、伪膜性肠炎等.近年来,CDI发病率、复发率、死亡率和治疗费用均明显增加,但其各种治疗方法均有局限性,尤其是抗生素治疗复发性艰难梭菌感染已面临许多棘手问题.目前证实肠道菌群失调和CDI感染关系密切,肠道菌群紊乱后导致艰难梭菌过度繁殖并释放毒素,可导致艰难梭菌感染.粪菌移植作为重建肠道菌群的重要方式,已成为复发性、难治性艰难梭菌感染最有效的治疗方式之一,不良反应极少.本文就国内外粪菌移植治疗艰难梭菌感染的研究进展作一综述.