Infantile liver failure syndrome type 1 (ILFS1) is a Mendelian disease due to biallelic mutations in the cytoplasmic leucyl-tRNA synthetase gene (LARS). This study aimed to report the clinical and molecular features of the first non-caucasian ILFS1 patient, providing reliable evidences for the definite diagnosis of ILFS1. The 2 years and 9 months old male patient was referred to the hospital with hepatosplenomegaly over 1 year. At age 17 months, he was found to have hepatosplenomegaly and anemia. Since then, he had been managed in different hospitals. The laboratory tests showed liver dysfunction, hypoproteinemia, coagulopathy and anemia, along with histologically-confirmed cirrhosis and fatty liver; however, the etiology remained undetermined. The subsequent SLC25A13 mutation analysis by means of prevalent mutation screening and Sanger sequencing only revealed a paternally-inherited mutation c.1658G>A, and no aberrant SLC25A13 transcripts could be detected from the maternal allele on cDNA cloning analysis, ruling out the possibility of citrin deficiency. Further target exome high-throughout sequencing of genes relevant to genetic liver diseases detected a paternal c.2133_2135del (p.L712del) and a maternal c.1183G>A (p.D395N) mutation in LARS gene. This finding was then confirmed by Sanger sequencing, and ILFS1 was thus definitely diagnosed. The child has been followed up till age 4 years, and his condition became stabilized.
Child, Preschool ; High-Throughput Nucleotide Sequencing ; Humans ; Leucine-tRNA Ligase ; genetics ; Liver Failure ; diagnosis ; genetics ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation

Objective　To study the effect of acute serious smoke inhalation injury to unilateral lung on contralateral lung and the therapeutic efficacy of massive bronchoscopic lavage with saline to the primary injured bronchoalveolus at early stage after smoke inhalation on mitigating the secondary damage of the other lung and so as to confirm the therapeutic validity of lung lavage to smoke inhalation injury. Methods　Fifteen mongrel dogs were insufflated with sawdust smoke into left lung and then randomized into 2 groups. The dogs in group A were maintained intravenous glucose saline transfusion and breathed air freely for 24 h after injury. Those in group B received a massive bronchoscopic lavage with 250 ml of saline to injured lung at 1 hour after injury and then were administrated similarly to those in group A. Gas exchange function of bilateral lungs in the process were observed and pathologic and phyiopathologic changes of the lung specimen were examined after the process. Results　While the total lavaging volume was kept to 250 ml, the liquid volume remained in left lung after each operating was from 90 ml to 140 ml. All animals had a significant decline in pulmonary function after smoke inhalation injury. PaO2 in group B decreased significantly soon after the lavage and then increased gradually to exceeding that in group A. The left lung showed serious edema similarly in two groups but in right lung the water content was less, dynamic and static compliance was more in group B than in group A. Conclusion　Bronchoalveolar massive lavage at early post-injury stage to injured lung after unilateral lung smoke inhalation injury can mitigate secondary damage of the non-injured lung. Lung lavage can decrease the intensity of secondary systemic inflammatory reaction and show a therapeutic validity to smoke inhalation injury.

Objective　To investigate the existence, intensit y and persisting time of biologic activity of bronchoalveolar lavage fluid (BALF ) collected from dogs with acute severe smoke inhalation injury in early post-i njury stage. Methods　BALF was collected 1 h after the est ablishment of acute severe sawdust smoke inhalation injury in 5 dogs, and the fl uid was perfused into the lungs of Wistar rats in the amount of 5 ml/kg (gro up C). Normal saline (group A) and BALF from normal dog (group B) were perfused into the lungs of rats and served as control. The respiratory rate, PaO2, lung water content and the expanding stability of lungs in all rats were determ ined at the time points of 4,12 and 24 h after the purfusion. Results　 Compared with the rats in group A and B, the rats in group C had higher mortality, wider range in RR, higher lung water content, PaO2 decreased obviou sly and lower lung expanding stability. The rats in control groups showed sl i ght mechanic obstruction in their airways in the course of experiment. Meanwhile ，the rats in group C showed higher oxidative activities and lower total anti-o xidative activities in lung tissues. Conclusion　It is certai n that the BALF collected from dogs with acute severe smoke inhalation injury in early post-injury stage could induce obvious injury in lung structure of norma l rats, showing certain mechanic obstruction in small airways. The injuring act ivity of the BALF can be alleviated ultimately 24 h after the perfusion of the B ALF.

BACKGROUNDChinese medicine plays an important role in hepatoprotective treatment. This study was conducted to investigate the protective effects of emodin and astragalus polysaccharides (APS) in a rat model of chronic hepatic injury.

METHODSChronic hepatic injury was induced by hypodermic injection of an olive oil solution containing 40% carbon tetrachloride (CCl(4)) twice a week, in addition to a diet of 79.5% maizena, 20% fat, 0.5% cholesterol, and 10% alcohol in the drinking water ad libitum for 12 weeks. Meanwhile, the rats were exposed to different concentrations of emodin (40 mg x kg(-1) x d(-1)), APS (200 mg x kg(-1) x d(-1)), combination drug (emodin 40 mg x kg(-1) x d(-1) combined with APS 200 mg x kg(-1) x d(-1)) and colchicine (0.1 mg x kg(-1) x d(-1)) in parallel by oral gavage (once a day for 12 weeks). At the end of 12 weeks, blood serum and liver tissue were taken. Serum was collected to determine the levels of total bilirubin (TBIL), alanine transaminase (ALT), aspartate transaminose (AST), and albumin (ALB). Liver and spleen indexes were assayed, followed by the measurements of the liver associated enzyme superoxide dismutase (SOD) and malondialdehyde (MDA). Histopathological changes were studied using optical microscopy.

RESULTSSplenohepatomegalia was alleviated and serum levels of TBIL and ALT were reduced in the groups treated with emodin and APS when compared to the control group. In addition, the ALB level in the APS and combination groups was higher. Similarly, the SOD activity of liver homogenates was significantly higher in the groups treated with emodin and APS, while administration of the herbal derivatives prevented the elevation in MDA levels. Histological analysis showed that the APS and combination groups significantly ameliorated the hepatic injury.

CONCLUSIONSCo-administration of emodin and APS demonstrated a synergistic action in reducing ALT and restoring ALB in the serum from a rat model of chronic hepatic injury. Emodin and APS may ameliorate the CCl(4)-induced hepatic injury in rats by elevating antioxidant-enzyme activities and reducing lipid peroxidation.

Alanine Transaminase ; blood ; Animals ; Astragalus Plant ; chemistry ; Carbon Tetrachloride ; toxicity ; Chronic Disease ; Emodin ; pharmacology ; Liver ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Polysaccharides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo establish a canine model of severe smoke inhalation injury on unilateral lung, in order to observe the pathomorphological changes in the injured lung within 24 postburn hours (PBHs).

METHODSTwenty five mongrel dogs were employed in the study and randomized into 3 groups. The left lung was injured by inhaling smoke produced by burning sawdust with sparing the right lung with a breathing tube in 10 dogs in group A. A conventional model of smoke inhalation injury to bilateral lungs was reproduced in 8 dogs in group B, and dogs in group C not subjected to smoke inhalation served as controls. Hemodynamic changes, blood gas analysis and the pathophysiologic changes in the lungs were observed within 24 PBHs.

RESULTSAll of the dogs in groups A and C survived. Hemodynamic indices in the dogs in groups A and C remained stable without showing signs of systemic hypoxia. The arterial oxygen partial pressure in dogs of group A was 65 +/- 5 mm Hg, and the oxygen saturation in the mixed blood was 0.64 +/- 0.04 at 24 PBHs, and they were much lower than those in group C but higher than those in group B. The pathological changes in the injured side of the lungs in group A were similar to those in group B with high consistency, and the changes, though milder, could also be identified in the contralateral uninjured lung. Five dogs died in the group B within 24 hours after smoke inhalation and the survivors showed signs of multiple organ failure.

CONCLUSIONThe canine model of acute severe unilateral pulmonary smoke inhalation injury was reproduced reliably, and could be an ideal model for the study on smoke inhalation injury.

Animals ; Burns, Inhalation ; Disease Models, Animal ; Dogs ; Lung Injury ; chemically induced ; Male ; Random Allocation ; Smoke Inhalation Injury

OBJECTIVETo evaluate the performance of vaporized hydrogen peroxide (VHP) for the bio-decontamination of the high efficiency particulate air (HEPA) filter unit.

METHODSSelf-made or commercially available bioindicators were placed at designated locations in the HEPA filter unit under VHP fumigation. The spores on coupons were then extracted by 0.5 h submergence in eluent followed by 200- time violent knocks.

RESULTSDue to the presence of HEPA filter in the box, spore recovery from coupons placed at the bottom of the filter downstream was significantly higher than that from coupons placed at the other locations. The gap of decontamination efficiency between the top and the bottom of the filter downstream became narrower with the exposure time extended. The decontamination efficiency of the bottom of the filter downstream only improved gently with the injection rate of H2O2 increased and the decontamination efficiency decreased instead when the injection rate exceeded 2.5 g/min. The commercially available bioindicators were competent to indicate the disinfection efficiency of VHP for the HEPA filter unit.

CONCLUSIONThis assay developed can detect all 16 β-lactams demanded by the European Union (EU). The whole procedure takes only 45 min and can detect 42 samples and the standards with duplicate analysis.

Air Filters ; Fumigation ; Hydrogen Peroxide ; chemistry

Quantitative structure-property relationships (QSPR) were developed to predict the pK(a) values of sulfa drugs via heuristic method (HM) and gene expression programming (GEP). The descriptors of 31 sulfa drugs were calculated by the software CODESSA, which can calculate constitutional, topological, geometrical, electrostatic, and quantum chemical descriptors. HM was also used for the preselection of 4 appropriate molecular descriptors. Linear and nonlinear QSPR models were developed based on the HM and GEP separately and two prediction models lead to a good correlation coefficient (R) of 0.90 and 0.95. The two QSPR models are tseful in predicting pK(a) during the discovery of new drugs and providing theory information for studying the new drugs.
Algorithms ; Gene Expression ; Models, Chemical ; Quantitative Structure-Activity Relationship ; Software ; Sulfonamides ; chemistry

OBJECTIVETo investigate the biological activities of the bronchoalveolar lavage fluid (BALF) harvested from dogs with smoke inhalation injury at early post injury stage.

METHODSBALF was harvested from normal dogs and those inflicted by smoke inhalation injury for the employment in the study. Ninety four Wistar rats were employed in the study and were randomly divided into A (n=28), B (n=29) and C (n=37) groups. The rats were perfused intra-tracheally with normal saline, BALF from normal dog and BALF from injured dog, respectively in A, B and C groups. Every 7 rats in each group were used before the perfusion as normal control. The rats in control group and those in A, B and C groups at 4, 12 and 24 hours after BALF perfusion were sacrificed. The survival rate and the pathomorphological gross and microscopic changes in pulmonary tissue in all groups were observed. In addition, the contents of prostaglandin F1alpha/thromboxane B2 (PGF1alpha/TXB2), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) in pulmonary tissue homogenization and the pulmonary capillary permeability were determined simultaneously.

RESULTSAll the rats in A and B groups survived, but nine in C group died before sacrificing. The BALF from dogs inflicted by smoke inhalation injury could cause rat lung exhibiting pathomorphological changes similar to those in rats inhaling smoke directly. The rat pulmonary tissue contents of PGF1alpha/TXB2 in A and B groups after the perfusion tended to increase, while that in C group decreased gradually (P <0.01). The rat pulmonary tissue contents of TNF-alpha and MPO content in A and B groups after the perfusion revealed no obvious change (P >0.05), while those in C group increased evidently at 4 hour after the perfusion and decreased thereafter (P <0.05-0.01). The pulmonary capillary permeability in C group was higher than that in A and B groups at 4 hour after the perfusion (P < 0.01).

CONCLUSIONThe BALF from canine lungs during the early stage of inhalation injury exhibited biological activities. The primary and secondary pulmonary injury could be prevented or ameliorated by massive pulmonary lavage during early post injury stage after smoke inhalation injury.

Animals ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; Dogs ; Lung ; pathology ; Male ; Rats ; Rats, Wistar ; Smoke Inhalation Injury ; pathology

OBJECTIVETo investigate the different velocity of polymorphonuclear neutrophil (PMN) infiltration, erythrocyte diapedesis and plasma exudation into the pulmonary tissue of the rats inflicted with smoke inhalation injury, so as to explore the different mechanisms of their existence in rat pulmonary tissue after inhalation injury.

METHODSThe rat smoke inhalation injury model was employed in the study. Wistar rats were inflicted with smoke inhalation injury, and then sacrificed at 1, 3, 6, 12 and 24 post injury hours (PIH). 131I-BSA, 99mTc-PMN or 99mTc-erythrocytes (RBC) were injected into rat pulmonary tissue 1 hour before sacrifice. Isotonic saline was infused into blood vessel to wash out circulation blood. Then the pulmonary tissue samples were harvested for gamma-value counting and then weighed. The infiltration of 131I-BSA, 99mTc-PMN or 99mTc-RBC in pulmonary tissue per gram and per minute was calculated, and MPO content was measured by phosphate T-tolidine method.

RESULTSThe amount of RBC diapedesis in rat lung tissue peaked at 1 PIH, decreased thereafter and approached to normal level at 24 PIH. The amount of PMN infiltration increased at 3 PIH, slightly decreased at 6 PIH but still higher than that in normal tissue, and increased again at 24 PIH. The pulmonary tissue content of MPO gradually increased from 1 PIH to 24 PIH. The pulmonary tissue content of 131I-BSA began to increase at 1 PIH and peaked at 6 PIH, and remained higher than that in normal tissue till 24 PIH.

CONCLUSIONEven though there was remarkable postburn increase in the erythrocyte diapedesis, neutrophil infiltration and albumin exudation with different peak time points (1, 3 and 6 PIH, respectively), Inflammation seemed not to be the premise of erythrocyte diapedesis, while the secondary inflammatory reaction might be the main cause of pulmonary edema.

Animals ; Capillary Permeability ; Exudates and Transudates ; metabolism ; Hemorrhage ; etiology ; Neutrophil Infiltration ; Rats ; Rats, Wistar ; Serum Albumin, Bovine ; metabolism ; Smoke Inhalation Injury ; complications ; metabolism

Objectives: To evaluate the changes of left atrial volume (LAV) and the maximum ostial cross-sectional area (CAS) of pulmonary vein (PV) in atrial fibrillation (AF) patients after circumferential pulmonary vein isolation radiofrequency catheter ablation (CPVA-RFCA) and to explore their relationship to AF recurrence by enhanced cardiac MRI evaluation. Methods: Our research included in 2 groups: Control group, n=20 healthy subjects and AF group, n=78 patients whom were classified into 2 subgroups as Paroxysmal AF subgroup, n=46 and Persistent AF subgroup, n=32; 66 patients received CPVA-RFCA and based on 6 months post-operative recurrence, they were divided into another set of 2 groups: AF recurrent subgroup, n=17 and Non-AF recurrent subgroup, n=49. Pre- and 6 months post-operative maximum ostial CSA of PV were measured by enhanced cardiac MRI, LAV were obtained by 3D reconstruction and the differences were compared between AF group and Control group, Paroxysmal AF subgroup and Persistent AF subgroup, AF recurrent subgroup and Non-AF recurrent subgroup; their relationships to AF recurrence were studied.Results: Compared with Control group, AF group had increased LAV and elevated ostial CSA of superior PV (SPV), both P<0.05. Compared with Paroxysmal AF subgroup, Persistent AF subgroup had increased LAV and elevated ostial CSA of SPV, both P<0.05. Compared with pre-operative condition, at 6 months after the operation, Non-AF recurrent subgroup showed reduced ostial CSAs in left SPV (LSPV), right SPV (RSPV), right inferior PV (RIPV) and decreased LAV, all P<0.05;while AF recurrent subgroup showed expanded RSPV and increased LAV,allP<0.05.Post-operative reductions of LAV and ostial CSA of SPV had close correlation; multivariate Logistic regression analysis indicated that LAV (HR=1.05, P<0.01)and ostial CSA of RSPV(HR=1.09,P=0.05)were related to AF recurrence after RFCA. Conclusions: CAPV-RFCA could reverse left atrial and PV remodeling in AF patients, LAV and ostial CSA of RSPV were related to post-operative AF recurrence.