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Objective: To study the effectiveness of liver transplantation (LT) in treating mitochondrial DNA depletion syndrome (MDS) caused by the MPV17 gene variant. Case presentation: A boy aged 2.8 years presented with edema of the lower limbs and abdomen, which persisted for over 10 days and was of unknown origin; this was accompanied by abnormal liver function, intractable hypoglycemia, and hyperlactatemia. During the second week of onset, he developed acute-on-chronic liver failure and was diagnosed with MDS due to homozygous variant c.293C>T in the MPV17 gene. Subsequently, he underwent LT from a cadaveric donor. At follow-up after 15 months, his liver function was found to be normal, without any symptoms. Additionally, a literature review was performed that included MDS patients with the MPV17 variant who underwent LT. The results demonstrated that the survival rates for MDS patients who underwent LT were 69.5%, 38.6%, 38.6%, and 38.6% at 1-year, 5-year, 10-year, and 20-year intervals, respectively. Sub-group analyses revealed the survival rate of MDS patients with isolated liver disease (83.33%, 5/6) was higher than that of hepatocerebral MDS patients (44.44%, 8/18). Fifteen variants were identified in the MPV17 gene, and patients with the c.293C>T (p.P98l) variant exhibited the highest survival rate. Conclusion: Hepatocerebral MDS patients without neurological symptoms may benefit from LT.
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BACKGROUND: Galactosemia is an autosomal recessive disorder resulting from an enzyme defect in the galactose metabolic pathway. The most severe manifestation of classic galactosemia is caused by galactose-1-phosphate uridylyltransferase (GALT) deficiency, and this condition can be fatal during infancy if left untreated. It also may result in long-term complications in affected individuals. CASE PRESENTATION: This report describes a patient whose initial clinical symptoms were jaundice and liver dysfunction. The patient's liver and coagulation functions did not improve after multiple admissions and treatment with antibiotics, hepatoprotective and choleretic agents and blood transfusion. Genetic analysis revealed the presence of two variants in the GALT gene in the compound heterozygous state: c.377 + 2dup and c.368G > C (p.Arg123Pro). Currently, the variant locus (c.377 + 2dup) in the GALT gene has not been reported in the Human Gene Mutation Database (HGMD), while c.368G > C (p.Arg123Pro) has not been reported in the Genome Aggregation Database (GnomAD) nor the HGMD in East Asian population. We postulated that the two variants may contribute to the development of classical galactosemia. CONCLUSIONS: Applications of whole-exome sequencing to detect the two variants can improve the detection and early diagnosis of classical galactosemia and, more specifically, may identify individuals who are compound heterozygous with variants in the GALT gene. Variants in the GALT gene have a potential therapeutic significance for classical galactosemia.
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Galactosemias , UTP-Hexosa-1-Fosfato Uridililtransferasa , Humanos , Galactosemias/genética , Galactosemias/diagnóstico , UTP-Hexosa-1-Fosfato Uridililtransferasa/genética , Masculino , Femenino , Mutación , LactanteRESUMEN
PURPOSE: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. METHODS: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. RESULTS: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. CONCLUSION: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.
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Antibacterianos , Ceftriaxona , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Ceftriaxona/efectos adversos , Masculino , Femenino , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Niño , Adulto , Persona de Mediana Edad , Preescolar , Antibacterianos/efectos adversos , Adolescente , Anciano , Lactante , Adulto Joven , Anciano de 80 o más Años , Recién Nacido , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Fosfatasa Alcalina/sangreRESUMEN
OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.
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Empiema , Hidrocefalia , Meningitis Neumocócica , Efusión Subdural , Lactante , Femenino , Masculino , Humanos , Niño , Recién Nacido , Adolescente , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/epidemiología , Meropenem , Vancomicina , Levofloxacino , Linezolid , Moxifloxacino , Estudios Retrospectivos , Rifampin , Streptococcus pneumoniae , CloranfenicolRESUMEN
BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. CONCLUSION: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.
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Gluconatos , Riñón , Zinc , Ratones , Animales , Ratones Endogámicos C57BL , Dosificación Letal Mediana , Zinc/toxicidadRESUMEN
Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.
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Background: Wilson's disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children. Materials and methods: The data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points. Results: Fifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001). Conclusion: Our study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.
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BACKGROUND: The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype. CASE SUMMARY: An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant's liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now. CONCLUSION: Based on the infant's clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.
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ABSTRACT: To develop a noninvasive model to predict significant fibrosis in children with chronic hepatitis B (CHB).A total of 116 CHB pediatric patients who underwent liver biopsy were included in the study. Liver histology, which is the gold standard for assessing fibrosis, was performed. Blood routine examination, coagulation function, liver biochemistry, viral serology, and viral load were analyzed. Receiver operating characteristic curve analysis was used to analyze the sensitivity and specificity of all possible cut-off values.Based on the correlation and difference analyses, 7 available clinical parameters (total bile acid, gamma-glutamyl transpeptidase [GGT], aspartate transaminase, direct bilirubin to total bilirubin ratio, alanine aminotransferase, prealbumin [PA], and cholinesterase) were included in the modeling analysis. A model to predict significant liver fibrosis was derived using the 2 best parameters (PA and GGT). The original model was . After the mathematical calculation, the G index=600â×âGGT/PA2 predicted significant fibrosis, with an area under the receiving operating characteristics (AUROC) curve of 0.733, 95% confidence interval (0.643-0.811). The AUROC of the G index (0.733) was higher than that of aminotransferase to platelet ratio index (APRI) (0.680) and Fibrosis index based on 4 factors (FIB-4) (0.601) in predicting significant fibrosis in children with CHB. If the values of the G index were outside the range of 0.28 to 1.16, 52% of children with CHB could avoid liver biopsy, with an overall accuracy of 75%.The G index can predict and exclude significant fibrosis in children with CHB, and it may reduce the need for liver biopsy in children with CHB.
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Hepatitis B Crónica/sangre , Cirrosis Hepática/diagnóstico , Hígado/patología , Modelos Estadísticos , Índice de Severidad de la Enfermedad , Biopsia , Niño , Preescolar , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Pruebas de Función Hepática/métodos , Masculino , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Estudios RetrospectivosRESUMEN
Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions. Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children's hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification. Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2% (n = 2,331) were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections (43.2%, n = 6,379). WHO Watch group antibiotics accounted for 70.4% of prescriptions (n = 12,915). The most prescribed antibiotic ATC classes were third-generation cephalosporins (41.9%, n = 7,679), followed by penicillins/ß-lactamase inhibitors (16.1%, n = 2,962), macrolides (12.1%, n = 2,214) and carbapenems (7.7%, n = 1,331). Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented.
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Intestinal myiasis caused by fly larvae parasitic in gastrointestinal tract was rare reported in children. We reported an infant with bloody diarrhea caused by intestinal myiasis. A 1 year and 7 months old boy presented with the only symptom of bloody diarrhea of unknown origin. In the second week of onset, numerous moving worms were observed in the bloody stool after bowel preparation with polyethylene glycol for colonoscopy. The bloody diarrhea disappeared after 1 week of combined therapy with albendazole and metronidazole. On follow-up after 6 months, the patient remained well without bloody diarrhea. In conclusion, intestinal myiasis being a rare disease that is very challenging to diagnose, physicians should remember it when they receive cases of bloody diarrhea with non-specific symptoms without any apparent cause.
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Miasis , Albendazol/uso terapéutico , Animales , Niño , Diarrea/etiología , Humanos , Lactante , Larva , Masculino , Miasis/diagnóstico , Miasis/tratamiento farmacológico , Enfermedades RarasRESUMEN
PURPOSE: This study aims to report the clinical features of an infant with CGL in a Chinese Zhuang ethnic family, whose family members were discovered to carry new pathogenic mutations in the BSCL2. PATIENTS AND METHODS: In this study, we report clinical and molecular investigations of CGL disease in a family of 4 members (parents and two sons). We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. RESULTS: The proband presented with skin pigmentation, hypertriglyceridemia and diabetes. WES identified a previously unreported compound heterozygous mutation in the BSCL2 (c.545_546insCCG heterozygous mutation and exon 3 heterozygous deletion) in the proband. His mother is a heterozygous carrier of the c.545_546insCCG mutation and his father and brother are carriers of the exon 3 heterozygous deletion. CONCLUSION: Compound heterozygous mutation of the BSCL2 (new c.545_546insCCG heterozygous mutation and new exon 3 heterozygous deletion) was detected in the proband with characteristic clinical manifestations of CGL2.
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AIM: The aim of this study was to evaluate the impact of zinc combined with probiotics (Bifico) on antibiotic-associated diarrhea (AAD) secondary to pneumonia. METHODS: A total of 50 patients with AAD secondary to pneumonia were randomly divided into a probiotics group (Bifico) and a combined group (zinc combined with Bifico) and 25 pneumonia patients without AAD as the control group. Serum levels of zinc, diamine oxidase (DAO) activity, D-lactate and intestinal flora [Bifidobacterium, Escherichia coli and Bifidobacterium/E. coli (B/E) ratio] were detected before and after intervention. RESULTS: The results showed that zinc combined with Bifico had significantly higher overall efficiency than Bifico alone for treatment of AAD secondary to pneumonia. Notably, the combined treatment increased the population of Bifidobacterium, while the number of E. coli was reduced, the B/E value was improved and DAO activity and D-lactate levels were markedly reduced. CONCLUSION: Patients with AAD secondary to pneumonia benefit from zinc supplementation of probiotic treatment.
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Antibacterianos/efectos adversos , Diarrea/tratamiento farmacológico , Neumonía/complicaciones , Probióticos/uso terapéutico , Zinc/uso terapéutico , Amina Oxidasa (conteniendo Cobre)/sangre , Bifidobacterium/aislamiento & purificación , Preescolar , Terapia Combinada , Diarrea/etiología , Diarrea/terapia , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Lactante , Masculino , Neumonía/tratamiento farmacológico , Zinc/sangreRESUMEN
BACKGROUND: Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors and is most often attributable to mutations in the lipoprotein lipase (LPL) gene. OBJECTIVES: The aim of this study was to identify rare mutations in the LPL gene causing severe hypertriglyceridemia. METHODS: A Chinese infant who presented classical features of severe hypertriglyceridemia recruited for DNA sequencing of the LPL gene. The pathogenicity grade of the variants was defined based on the prediction of pathogenicity using in silico prediction tools. Review some studies to understand the molecular mechanisms underlying the severe hypertriglyceridemia. RESULTS: We identified a rare mutation in the LPL gene causing severe hypertriglyceridemia: a nucleotide substitution (c.836T>G) resulting in a leucine to arginine substitution at position 279 of the protein (p.Leu279Arg).The pathogenicity of the variant was predicted by in silico analysis using PolyPhen2 and SIFT prediction programs, which indicated that mutation p.Leu279Arg is probably harmful. We have also reviewed published studies concerning the molecular mechanisms underlying severe hypertriglyceridemia. A missense mutation in the 6 exon of the LPL gene is reportedly associated with LPL deficiency. CONCLUSIONS: We have here identified a rare pathogenic mutation in the LPL gene in a Chinese infant with severe hypertriglyceridemia.
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OBJECTIVE: To analyze the effects of ursodeoxycholic acid (UDCA) on the mRNA expression of multidrug resistance protein 3 (MDR3) and farnesoid X receptor (FXR) in infants with cholestatic hepatitis. METHODS: Twenty-eight infants who were diagnosed with cholestatic hepatitis between July 2008 and July 2010 were included in the study. These patients received treatment with UDCA. The mRNA expression levels of MDR3 and FXR were measured by real-time quantitative RT-PCR with SYBR Green I, before and after treatment with UDCA. RESULTS: After treatment with UDCA, the infants with cholestatic hepatitis had significantly decreased serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and gamma-glutamyltransferase (P<0.05) and significantly increased mRNA expression of MDR3 (P<0.05). No significant change in mRNA expression of FXR was observed, however (P>0.05). CONCLUSIONS: UDCA improves liver function indices in infants with cholestatic hepatitis, which may be related to up-regulated mRNA expression of MDR3.
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Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Colestasis/tratamiento farmacológico , Hepatitis/tratamiento farmacológico , ARN Mensajero/análisis , Receptores Citoplasmáticos y Nucleares/genética , Ácido Ursodesoxicólico/uso terapéutico , Colestasis/complicaciones , Colestasis/metabolismo , Femenino , Regulación de la Expresión Génica , Hepatitis/etiología , Hepatitis/metabolismo , Humanos , Lactante , Masculino , Ácido Ursodesoxicólico/farmacologíaRESUMEN
BACKGROUND: This study aimed to evaluate the genetic effect of the NR1H4 gene in the pathogenesis of idiopathic infantile cholestasis of Chinese subjects in Guangxi, China. METHODS: Seventy-eight patients with idiopathic infantile cholestasis served as a study group and 95 infants without cholestasis as controls. Genomic DNA was extracted from peripheral venous blood leucocytes by phenol chloroform procedures. Polymerase chain reaction (PCR) was used to amplify all coded exons of NR1H4, and single-strand conformation polymorphism (SSCP) was used to analyze all amplification fragments. The PCR products with abnormal bands in SSCP were sequenced using an ABI 3100 sequencer. RESULTS: A novel heterozygous termination codon mutation in NR1H4 exon 5 (NR1H4 R176X, CGA-TGA) was found in one of the 78 patients. The patient with mutation R176X had high levels of bilirubin, alanine aminotransferase, γ-glutamyltransferase, cirrhosis and ascites despite biliary tract flushing procedures and drug therapy. In the other patients and controls, no mutation was detected. CONCLUSIONS: Heterozygous termination codon mutation of NR1H4 R176X was found in idiopathic infantile cholestasis. The novel mutation is useful to establish particular characteristics for differential diagnosis of idiopathic infantile cholestasis and to determine the influence of such gene defects in the prognosis.
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Pueblo Asiatico/genética , Colestasis/genética , Codón de Terminación , Mutación , Receptores Citoplasmáticos y Nucleares/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Codón de Terminación/genética , Diagnóstico Diferencial , Exones , Heterocigoto , Humanos , Lactante , Reacción en Cadena de la Polimerasa , Pronóstico , Receptores Citoplasmáticos y Nucleares/sangreRESUMEN
OBJECTIVE: To study hepatic NF-κB level following endotoxemic liver injury, and its relationship with hepatic TNF-α and IL-6 levels in young rats. METHODS: Forty 18-day-old rats were randomly assigned to a normal control and an endotoxemia group. Endotoxemia was induced by lipopolysaccharide injection (LPS, 5 mg/kg). The endotoxemia group was subdivided into four groups sampled at 2, 6, 12 and 24 hrs after LPS injection (n=8 each). Pathological changes in liver cells were observed under a light microscope. TNF-α and IL-6 levels in liver tissue homogenates were measured using ELISA. Reitman-Frankel was used to measure serum ALT concentrations. NF-κB activation level in liver tissues was detected by immunohistochemistry. RESULTS: Liver tissue injury was the most obvious 6 hrs after LPS injection under the light microscope, and the damage rating of liver tissues was significantly higher in the endotoxemia group than that in the normal control group at all time points (P<0.05). ALT levels in the endotoxemia group were significantly higher than those in the normal control group 6, 12 and 24 hrs after LPS injection (P<0.05). NF-κB p65 protein expression in liver cells (percentage of nuclear positive cells) in the endotoxemia groups was significantly higher than that in the normal control group (P<0.05). TNF-α and IL-6 levels in liver tissue homogenates in the endotoxemia groups were significantly higher than those in the normal control group 6 and 12 hrs after LPS injection (P<0.05). CONCLUSIONS: Endotoxemia can cause liver injury, resulting in liver cell damage and changes in liver function. NF-κB activation is involved in endotoxemic liver injury which may be mediated by inflammatory cytokines TNF-α and IL-6 synthesis.
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Endotoxemia/complicaciones , Hepatopatías/etiología , Hígado/química , FN-kappa B/análisis , Alanina Transaminasa/sangre , Animales , Conducta Animal , Femenino , Interleucina-6/análisis , Hígado/patología , Hepatopatías/metabolismo , Masculino , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVE: To investigate the relationship of the promoter of matrix metalloproteinase-9 (MMP-9) gene polymorphisms with the susceptibility and clinical features of Helicobacter pylori (H. pylori)-related chronic gastritis and duodenal ulcer in children. METHODS: One hundred children with chronic gastritis, 32 children with duodenal ulcer and 102 healthy children were enrolled.The promoter of MMP-9-1562C/T gene polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and sequencing. MMP-9 mRNA expression in gastric mucosa was confirmed by reverse transcription polymerase chain reaction. RESULTS: The genotype distributions and allele frequencies of MMP-9-1562C/T gene polymorphisms were similar in gastric upper gastrointestinal disease and healthy subjects. The relative risk for H.pylori infection in C/C genetype carriers was 3.1 times as high as that in T allele (C/T+T/T) carriers in children with chronic gastritis. MMP-9-1562 C/T gene polymorphisms did not affect MMP-9 mRNA expression level. CONCLUSIONS: These data suggest that MMP-9-1562 C/T gene polymorphisms are not associated with susceptibility to chronic gastritis and duodenal ulcer in children. The C/C genotype of MMP-9-1562 C/T gene polymorphism might be associated with H.pylori infection.
Asunto(s)
Úlcera Duodenal/genética , Gastritis/genética , Infecciones por Helicobacter/genética , Helicobacter pylori , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Adolescente , Niño , Preescolar , Enfermedad Crónica , Úlcera Duodenal/etiología , Femenino , Gastritis/etiología , Genotipo , Infecciones por Helicobacter/complicaciones , Humanos , MasculinoRESUMEN
AIM: To evaluate the role of genetic factors in the pathogenesis of idiopathic infant cholestasis. METHODS: We performed a case-control study, including 78 infants with idiopathic infant cholestasis and 113 healthy infants as controls. Genomic DNA was extracted from peripheral venous blood leukocytes using phenol chloroform methodology. Polymerase chain reaction was used to amplify the multidrug resistance protein 3 (MDR3) R652G fragment, and products were sequenced using the ABI 3100 Sequencer. RESULTS: The R652G single nucleotide polymorphism (SNP) was significantly more frequent in healthy infants (allele frequency 8.0%) than in patients (allele frequency 2.60%) (P < 0.05), odds ratio, 0.29; 95% confidence interval, 0.12-0.84. The conjugated bilirubin in patients with the AG genotype was significantly lower than in those with the AA genotype (44.70 +/- 6.15 micromol/L vs 95.52 +/- 5.93 micromol/L, P < 0.05). CONCLUSION: MDR3 R652G is negatively correlated with idiopathic infant cholestasis. Children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis.