Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment

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 16 S r DNA 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 followup. During follow-up,one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16 S r DNA 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.

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

内界膜翻转填塞与内界膜剥除治疗高度近视黄斑裂孔视网膜脱离的Meta分析

目的:评价玻璃体切除(PPV)联合内界膜(ILM)翻转填塞或ILM剥除在治疗高度近视黄斑裂孔视网膜脱离(MHRD)中解剖学及视力恢复疗效。方法:从中国知网(CNKI)、维普(VIP)、万方数据库(Wan Fang Database)、PubMed、EMbase、The Cochrane Library、Europe PMC、Nature数据库中检索文献,检索时间均为建库至2018-09。以术后6mo为随访时间节点,观察黄斑裂孔闭合、原发性视网膜复位及BCVA情况。采用Review 5.3及Stata 15.1软件进行Meta分析。结果:本研究包括8项研究266眼。ILM翻转填塞在黄斑裂孔闭合率方面优于ILM剥除(RR=2.05,95%CI 1.69～2.49,P<0.00001),在原发性视网膜复位率方面无差异(RR=1.04,95%CI 0.98～1.12,P=0.21),在术后6mo两组BCVA均较术前明显提高(分别为:RR=0.44,95%CI 0.33～0.55,P<0.00001;RR=0.29,95%CI 0.10～0.48,P=0.003),两组间BCVA改善程度的差异结果存在异质性,其结论可能不稳定,尚需更多可靠数据证明。结论:PPV联合ILM翻转填塞在治疗高度近视MHRD患者中更有效。

Clinical Features and Genetic Analysis of Pediatric Patients with Alagille Syndrome Presenting Initially with Liver Function Abnormalities

Alagille syndrome （AGS） is a multisystem disorder and caused by mutations in JAG1 or NOTCH2 gene. The diagnosis of AGS is hampered by its highly variable clinical manifestations. We performed a retrospective analysis on 16 children diagnosed as having AGS in recent five years in our hospital. Cholestasis was seen in 15 patients （93.8%）, heart disease in 12 （75%）, characteristic facies in 7 （43.8%）, and butterfly vertebrae in 7 （43.8%）. Ophthalmology examination was not performed on all the patients. Further, serum biochemical parameters were compared between AGS and 16 biliary atresia （BA） patients who were confirmed by surgery. Elevated liver enzymes were seen in all the patients. Serum total cholesterol （TC） （P=0.0007）, alanine aminotransferase （ALT） （P=0.0056）, aspartate aminotransferase （AST） （P=0.0114）, gamma-glutamyl transferase （GGT） （P=0.035） and total bile acid （TBA） levels （P=0.042） were significantly elevated in AGS patients compared to those in BA cases. However, there were no significant differences in serum total bilirubin （TB）, conjugated bilirubin （CB） and albumin （ALB） between the two groups. We identified 14 different JAG1 gene variations and 1 NOTCH2 gene mutation in 16 Chinese AGS patients. Our study suggested clinical features of AGS are highly variable and not all patients meet the classical diagnostic criteria. It was suggested that hypercholesterolaemia and significantly elevated GGT, TBA and ALT may be helpful to diagnose AGS. Genetic testing is integral in the diagnosis of AGS.

青光眼滤过术后抗瘢痕形成药物的研究新进展

青光眼滤过术是目前抗青光眼药物及激光治疗无法控制眼压时的首选手术方式,其术后滤过泡瘢痕形成是导致手术失败的重要原因。目前在抗青光眼术后瘢痕的基础及临床研究上有一定的进展,但寻求一种高效、安全、稳定的药物治疗青光眼滤过术后瘢痕形成仍是一个需要继续努力解决的问题。本文就近3a所发表的关于青光眼滤过术后抗瘢痕形成的相关药物研究作一综述。

3′-Daidzein sulfonate sodium protects against memory impairment and hippocampal damage caused by chronic cerebral hypoperfusion

3′-Daidzein sulfonate sodium（DSS） is a new synthetic water-soluble compound derived from daidzein,a soya isoflavone that plays regulatory roles in neurobiology.In this study,we hypothesized that the regulatory role of DSS in neurobiology exhibits therapeutic effects on hippocampal damage and memory impairment.To validate this hypothesis,we established rat models of chronic cerebral hypoperfusion（CCH） by the permanent occlusion of the common carotid arteries using the two-vessel occlusion method.Three weeks after modeling,rat models were intragastrically administered 0.1,0.2,and 0.4 mg/kg DSS,once a day,for 5 successive weeks.The Morris water maze test was performed to investigate CCH-induced learning and memory deficits.TUNEL assay was used to analyze apoptosis in the hippocampal CA1,CA3 regions and dentate gyrus.Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal CA1,CA3 regions and dentate gyrus.Western blot analysis was performed to investigate the phosphorylation of PKA,ERK1/2 and CREB in the hippocampal PKA/ERK1/2/CREB signaling pathway.Results showed that DSS treatment greatly improved the learning and memory deficits of rats with CCH,reduced apoptosis of neurons in the hippocampal CA1,CA3 regions and dentate gyrus,and increased the phosphorylation of PKA,ERK1/2,and CREB in the hippocampus.These findings suggest that DSS protects against CCH-induced memory impairment and hippocampal damage possibly through activating the PKA/ERK1/2/CREB signaling pathway.

3′-Daidzein sulfonate sodium improves mitochondrial functions after cerebral ischemia/reperfusion injury

3′-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein（an active ingredient of the kudzu vine root）. It has been shown to have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan to study the mechanism of its protective effect. 3′-Daidzein sulfonate sodium was injected in rats after cerebral ischemia/reperfusion injury. Results showed that 3′-daidzein sulfonate sodium significantly reduced mitochondrial swelling, significantly elevated the mitochondrial membrane potential, increased mitochondrial superoxide dismutase and glutathione peroxidase activities, and decreased mitochondrial malondialdehyde levels. 3′-Daidzein sulfonate sodium improved the structural integrity of the blood-brain barrier and reduced blood-brain barrier permeability. These findings confirmed that 3′-daidzein sulfonate sodium has a protective effect on mitochondrial functions after cerebral ischemia/reperfusion injury, improves brain energy metabolism, and provides protection against blood-brain barrier damage.

Chinese clinical practice guidelines for acute infectious diarrhea in children

Background The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. Data sources The experts group of evidence development put forward clinical problems, collects evidence, forms prelimi-nary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic 'acute diarrhea' or 'enteritis' and 'adolescent' or 'child' or'Pediatric patient' or 'Baby' or 'Infant'. Results For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recom-mended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Sac-charomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racec-adotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease;otherwise, antibiotics are not recommended. Conclusion The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects

F-652 is a recombinant fusion protein consisting of two human interleukin-22(IL-22)molecules linked to an immunoglobulin constant region(IgG 2-Fc).IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection.The safety,pharmacokinetics(PK),tolerability,and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized,double-blind,placebo-controlled study.Following single-dose subcutaneous(SC)injection of F-652 at 2.0µg/kg into healthy subjects,six out of six subjects experienced delayed injection site reactions,which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing.F-652 was then administered to the healthy subjects via an intravenous(IV)infusion at 2.0,10,30,and 45µg/kg.No severe adverse event(SAE)was observed during the study.Among the IV-dosed cohorts,eye and skin treatment emergent adverse events(TEAEs)were observed in the 30 and 45µg/kg cohorts.F-652 IV dosing resulted in linear increases in C max and AUC(0–t),and the T 1/2 ranged from 39.4 to 206h in the cohorts.An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A,C-reactive protein,and FIB,and decreased serum triglycerides.The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45μg/kg.In conclusion,IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties.These results warrant further clinical development of F-652 to treat inflammatory diseases.

The value of radionuclide hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis of infantile persistent jaundice

The aim of this study was to investigate the value of technetium etifenin injection(^(99m)Tc-EHIDA)hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis between infantile hepatitis syndrome and biliary atresia.^(99m)Tc-EHIDA hepatobiliary scintigraphy in combination with duodenal fluid examination was used for evaluation in 84 infants with persistent infantile jaundice.For diagnosing biliary atresia,the sensitivity and specificity of scintigraphy were 100% and 74.5%,respectively;the sensitivity and specificity of scintigraphy in combination with duodenal fluid examination were 100% and 100%,respectively.In conclusion,hepatobiliary scintigraphy,which is a noninvasive,safe,valuable examination method,in combination with examination of duodenal fluid,is of value for the differential diagnosis between infantile hepatitis syndrome and biliary atresia.