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Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC 50 value of 4.23 μM. Treatment with OB (2.5, 5 mg·kg -1 ·d -1 , i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-β/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H 1 receptor antagonist, but also acted as a selective antagonist of 5HTR 2A . In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR 2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR 2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR 2A /c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR 2A . We conclude that spinal 5HTR 2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR 2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR 2A -specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR 2A /c-FOS pathway. Our findings have supported that spinal 5HTR 2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

GULP1 is an engulfment adaptor protein containing a phosphotyrosine-binding (PTB) domain, and existing studies have shown that it can promote glucose uptake in 3T3-L1 adipocytes. To further explore key metabolically related differential genes downstream of GULP1, this study conducted transcriptome analysis on adipocytes and skeletal muscle cells overexpressing GULP1. Subsequently, abnormally expressed genes were subjected to bioinformatic analysis, and real-time fluorescent quantitative PCR (qRT-PCR) was used for mutual validation with transcriptome sequencing. The results indicated that, with a threshold of P < 0.05 and |Log 2 FoldChange| ≥ 1 for screening differentially expressed genes, compared with control cells, there were 278 upregulated and 263 downregulated genes in adipocytes overexpressing GULP1. Metabolism-related GO (Gene Ontology) terms included cholesterol biosynthetic process, cholesterol metabolic process, response to lipopolysaccharide, lipid metabolic process, etc. A total of 52 metabolically related differentially expressed genes were enriched in 10 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, with lipid metabolism being highly enriched. In skeletal muscle cells overexpressing GULP1, there were 280 upregulated and 302 downregulated genes, with metabolism-related GO terms including hormone metabolic process, response to lipopolysaccharide, one-carbon metabolic process, etc. A total of 86 metabolically related differentially expressed genes were enriched in 10 KEGG pathways, with amino acid metabolism, lipid metabolism, and carbohydrate metabolism being highly enriched. GULP1's biological functions are extensive, including lipid metabolism and oncology. This study, through transcriptomics and bioinformatic analysis, identified key metabolically related differential genes downstream of GULP1, obtained metabolically related differential genes and signaling pathways after GULP1 overexpression, providing important theoretical basis for future research on GULP1 downstream target genes.

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge in synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, is particularly significant for amine synthesis in the pharmaceutical, agrochemical, and fine chemical industries. However, the existing methods usually require specific substrate combinations to achieve precise regio- and stereoselectivity, which limits their practical utility. Protocols allowing for regiodivergent hydroaminoalkylation from the same starting materials, controlling both regiochemical and stereochemical outcomes, are currently absent. Herein, we report a ligand-controlled, regiodivergent nickel-catalyzed hydroaminoalkylation of unactivated alkenes with N -sulfonyl amines. The reaction initiates with amine dehydrogenation and involves aza-nickelacycle intermediates. Tri tert -butylphosphine promotes branched regioselectivity and syn diastereoselectivity, whereas ethyldiphenylphosphine enables linear selectivity, yielding regioisomers with inverse orientation. Systematic evaluation of diverse monodentate phosphine ligands reveals distinct regioselectivity cliffs, and % V bur ( min ), a ligand steric descriptor, was established as a predictive parameter correlating ligand structure to regioselectivity. Computational investigations supported experimental findings, offering mechanistic insights into the origins of regioselectivity. Our method provides an efficient and predictable route for amine synthesis, demonstrating broad substrate scope, excellent tolerance toward various functional groups, and practical advantages. These include the use of readily available starting materials and cost-effective nickel(II) salts as precatalysts.

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 μmol·L -1 ., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: To establish a method for rapid detection of DB-WAX capillary column and determination of the workplace air in 30 kinds of volatile organic pollutants. Methods: In August 2020, N-pentane, n-hexane, methylcyclohexane, octane, Acetone, ethyl acetate, butanone, benzene, 3-pentanone, trichloroethylene, tetrachloroethylene, toluene, butyl acetate, 2-hexanone, Isoamyl acetate, ethylbenzene, p-xylene, m-xylene, amyl acetate, o-xylene, chlorobenzene, styrene, cyclohexanone, P-chlorotoluene, bromobenzene, M-dichlorobenzene, p-dichlorobenzene, O-dichlorobenzene, o-Chlorotoluene, 1, 2 , 4-trichlorobenzene of 30 kinds of substances in air were collected by activated carbon tube. After analysis by carbon disulfide, the analytical solution was analyzed by DB-WAX column and determined by FID detector. Results: The above 30 kinds of volatile organic pollutants had good separation effect, the correlation coefficient of the standard curve was above 0.999, the relative standard deviation was 0.1%-3.2%, the desorption efficiency was 77.0%-117.1% , the lower limit of quantitation was 0.33-5.33 μg/ml, and the lowest quantitation concentration was 0.22-3.55 mg/m(3), the recoveries ranged was 95.4%-104.9%. Conclusion: The method can effectively separate and accurately determine 30 volatile organic compounds in these workplaces, and the method is simple and quick.

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies., Competing Interests: AC, Y-JL and Z-XZ were employed by the company Guangzhou Mendel Genomics and Medical Technology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Tang, Tan, Yan, Sun, Guo, Qian, Chen, Luo, Zheng, Zhang, Jia and Liu.)

Background: Many genetic syndromes (GSs) have distinct facial dysmorphism, and facial gestalts can be used as a diagnostic tool for recognizing a syndrome. Facial recognition technology has advanced in recent years, and the screening of GSs by facial recognition technology has become feasible. This study constructed an automatic facial recognition model for the identification of children with GSs., Results: A total of 456 frontal facial photos were collected from 228 children with GSs and 228 healthy children in Guangdong Provincial People's Hospital from Jun 2016 to Jan 2021. Only one frontal facial image was selected for each participant. The VGG-16 network (named after its proposal lab, Visual Geometry Group from Oxford University) was pretrained by transfer learning methods, and a facial recognition model based on the VGG-16 architecture was constructed. The performance of the VGG-16 model was evaluated by five-fold cross-validation. Comparison of VGG-16 model to five physicians were also performed. The VGG-16 model achieved the highest accuracy of 0.8860 ± 0.0211, specificity of 0.9124 ± 0.0308, recall of 0.8597 ± 0.0190, F1-score of 0.8829 ± 0.0215 and an area under the receiver operating characteristic curve of 0.9443 ± 0.0276 (95% confidence interval: 0.9210-0.9620) for GS screening, which was significantly higher than that achieved by human experts., Conclusions: This study highlighted the feasibility of facial recognition technology for GSs identification. The VGG-16 recognition model can play a prominent role in GSs screening in clinical practice., (© 2021. The Author(s).)

Background: This study aimed to evaluate the risk factors of HCC development in patients with hepatitis B virus (HBV)-related DC and who underwent long-term antiviral therapy., Methods: Data from 308 patients with HBV-related DC and long-term antiviral therapy were collected and retrospectively reviewed. Cox regression analysis was used to analyze independent risk factors of HCC development., Results: Data from 129 patients with definite records were analyzed. The median follow-up time was 5 years (range, 1 to 8 years). At the end of the follow-up, 41 (31.8%) patients developed HCC, and the time from DC diagnosis to HCC incidence who received antiviral therapy was 4.4 years (range, 1-7 years). The incidence of HCC was higher in males (30/78, 38.5%) than in females (11/51, 21.6%) ( P  = 0.04). Patients who developed HCC were significantly older than those who did not develop HCC ( P  < 0.01). The incidence of HCC in patients receiving nucleoside analogues, nucleotide analogues, and combination therapy was 34.7%, 38.1%, and 33.3%, respectively, and the difference showed no significant differences ( P  = 0.95). Multivariate Cox regression analysis demonstrated that male gender and age ≥50 years are independent risk factors of HCC development (OR = 2.987 and 2.408; 95% CI (1.301-6.858) and (1.126-5.149); P  = 0.01 and 0.02, respectively)., Conclusion: The risk of HCC remains to be high in patients with HBV-related DC, especially in males aged ≥50 years., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Dong-Mei Zhu et al.)

Objective: To assess the efficacy and long-term outcome of percutaneous balloon aortic valvuloplasty (PBAV) for children with congenital aortic stenosis (CAS) and to explore risk factors for significant aortic regurgitation (AR) and reintervention after PBAV during follow up. Methods: This was a retrospective study. Children (≤18 years old) with CAS, who underwent PBAV in Guangdong Provincial Hospital from January 2004 to December 2018, were included in this study. Demographic, preoperative transthoracic echocardiography (TTE) and surgical data were collected. Postoperative complications were closely observed, and the patients were followed up at 1, 6, 12 months after the operation, and then at one year interval thereafter. Endpoint events included significant AR and reintervention. Reintervention was defined as any intervention that needed to be performed on the valve for various reasons, including re-PBAV, surgical valvuloplasty and valve replacement. Significant AR was defined as AR grade≥3 by TTE criteria. The results of the last TTE examination before the end of the study were collected. The Kaplan-Meier curve for long-term AR-free and intervention-free survival was plotted. Cox regression model was used to further analyze the risk factors for significant AR and reintervention after PBAV in CAS patients. Results: A total of 55 patients were enrolled in this study, and the age was 4.6(1.6, 6.5) years, with 37(67.3%) males. The peak systolic valve gradient fell from (80.3±30.6)mmHg to (38.5±18.5)mmHg( P <0.001, 1 mmHg=0.133 kPa). Surgical success rate was 89% (49/55). Acute post-PBAV AR occurred in 18 patients, including 3 patients with RA≥3 grade. In-hospital complications occurred in 6 patients (2 deaths, 2 cases of transient arrhythmia, and 2 cases of femoral artery embolization). Fifty patients accomplished the follow-up and the follow-up time was 6.2(3.4, 8.5) years. Significant AR was found in 20 patients. Significant AR-free survival rate was 53% at 5 years and 19% at 10 years. Reintervention was performed in 11 patients (4 with valvuloplasty and 7 with valve replacement), and the 5-year and 10-year intervention-free survival rates were 87% and 62%, respectively. Multivariate Cox regression analysis showed that acute post-PBAV AR was a risk factor for long-term significant AR ( HR =2.398, 95% CI 1.007-5.712, P =0.048). Post-PBAV residual pressure gradient ≥ 35 mmHg ( HR =4.747, 95% CI 1.116-19.329, P =0.030)and acute post-PBAV AR ( HR =5.104, 95% CI 1.083-24.065, P =0.039)were risk factors for re-intervention. Conclusions: PBAV is safe and effective in the treatment of CAS in children, but attention should be paid on significant AR post procedure. Acute post-PBAV AR is a risk factor for re-intervention and significant AR post PBAV, and high post-PBAV residual pressure gradient is a risk factor for re-intervention.

The global prevalence of nonalcoholic steatohepatitis (NASH) increases incredibly. NASH ends up to advanced liver disease, which is highly threatening to human health. Currently, treatment of NASH is very limited. Acetyl-CoA carboxylases (ACC1/ACC2) are proved as effective drug targets for NASH. We aimed to develop novel ACC inhibitors and evaluate their therapeutic value for NASH prevention. ACC inhibitors were obtained through structure-based drug design, synthesized, screened from ACC enzymatic measurement platform and elucidated in cell culture-based assays and animal models. The lipidome and microbiome analysis were integrated to assess the effects of WZ66 on lipids profiles in liver and plasma as well as gut microbiota in the intestine. WZ66 was identified as a novel ACC1/2 inhibitor. It entered systemic circulation rapidly and could accumulate in liver. WZ66 alleviated NASH-related liver features including steatosis, Kupffer cells and hepatic stellate cells activation in diet-induced obese mice. The triglycerides (TGs) and other lipids including diglycerides (DGs), phosphatidylcholine (PC) and sphingomyelin (SM) were decreased in WZ66-treated mice as evidenced by lipidome analysis in livers. The lipids profiles in plasma were also altered with WZ66 treatment. Plasma TG were moderately increased, while the activation of SREBP1c was not detected. WZ66 also downregulated the abundance of Allobaculum, Mucispirillum and Prevotella genera as well as Mucispirillum schaedleri species in gut microbiota. WZ66 is an ideal lead compound and a potential drug candidate deserving further investigation in the therapeutics of NASH.

Background: Pulmonary artery hypertension associated with congenital heart disease (PAH-CHD) occurs predominantly among patients with uncorrected CHD. Treatment of severe pediatric PAH-CHD remains a major intractability. This study evaluated the predictors and prognoses of children with PAH-CHD who underwent surgical correction., Methods: The data for 59 children with severe PAH-CHD who underwent surgical correction, with or without postoperative medication, between May 2011 and June 2015 at the Guangdong Provincial People's Hospital were analyzed retrospectively. A regression analysis, receiver-operating characteristic (ROC) curves, and Kaplan-Meier curves were used for survival analysis., Results: Fifty-nine children with severe PAH-CHD underwent heart catheterization and correction, with or without specific anti-PAH drugs postoperatively, were included in this study. The pulmonary pressure, heart function, and ending events were observed and median observation period was 49 ± 20 months. Twenty-eight patients (50%) received at least one additional anti-PAH drug after correction. The survival rate after 2 years was 91.5% (54/59); two patients were in a critical condition, and three were lost to follow-up. Twelve patients (29%) still received over one additional PAH-specific therapy at follow-up, whereas 42 (75%) had successfully stopped drug treatment. Two patients (3.5%) died and one underwent a second thoracotomy to remove the ventricular septal defect patch. Acute vasoreactivity test (AVT) criteria had limited efficacy in predicting pediatric PAH-CHD, whereas pulmonary vascular resistance (PVR) ≤ 6.65 Wood units (WU)/m or PVR/systemic vascular resistance (SVR) ≤ 0.39 during AVT indicated a good prognosis after surgical correction with an AUC of 98.3% (95% confidence interval [CI]: 96.0-100%), 98.4% (95% CI: 96.0-100%) sensitivity of 100%, 100% and specificity of 82.1%, 92.9%, respectively., Conclusions: Although the criteria for positive AVT currently used are unsuitable for pediatric patients with PAH-CHD, PVR and PVR/SVR during AVT are excellent predictors of outcome in pediatric PAH-CHD. Surgery aided by anti-PAH drugs is an effective strategy and should be recommended for severe pediatric PAH-CHD with PVR ≤ 6.65 WU/m and PVR/SVR ≤ 0.39 after iloprost aerosol inhalation.

Background: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate factors associated with immediate therapeutic outcomes and restenosis during medium-term follow-up., Methods: The study included 158 infants with PVS who underwent PBPV from January 2009 to July 2015. Demographic characteristics and patient records were reviewed, including detailed hospitalization parameters, hemodynamic data before and immediately after balloon dilation, cineangiograms, and echocardiograms before PBPV and at each follow-up. All procedures were performed by more than two experienced operators., Results: Immediately after balloon dilation, the pressure gradient across the pulmonary valve decreased from 73.09 ± 21.89 mmHg (range: 43-151 mmHg) to 24.49 ± 17.00 mmHg (range: 3-92 mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34 ± 23.44 mmHg (range: 60-174 mmHg) to 52.07 ± 18.89 mmHg (range: 22-134 mmHg; P < 0.001). Residual transvalvular pressure gradients of 67.31 ± 15.19 mmHg (range: 50-92 mmHg) were found in 8.2% of patients, indicating poor therapeutic effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8% underwent reintervention by balloon dilation or surgical repairs. Further analysis demonstrated that the balloon/annulus ratio showed statistically significant differences (P < 0.05) among groups with different therapeutic effects and between the restenosis and no-stenosis groups. Binary logistic regression analysis further revealed that higher balloon/annulus ratio (odds ratio: 0.005, 95% confidence interval: 0-0.39) was an independent protective factor for restenosis. The rate of severe complications was 1.9%., Conclusions: PBPV is a definitive therapy for infants with PVS based on its effectiveness, feasibility, and safety. Restenosis upon medium-term follow-up is relatively rare.

The objectives of this study was to through monitoring the 1st industrial scale garage-type dry fermentation (GTDF) MSW biogas plant in Bin County, Harbin City, Heilongjiang Province, China, to investigate its anaerobic digestion (AD) performance and the stability of process. After a monitoring period of 180days, the results showed that the volumetric biogas production of the digesters and percolate tank was 0.72 and 2.22m(3) (m(3)d)(-1), respectively, and the specific biogas yield of the feedstock was about 270m(3)CH4tVS(-1), which indicated that the GTDF is appropriate for the Chinese MSW. This paper also raised some problems aimed at improving the process stability and AD efficiency., (Copyright © 2016. Published by Elsevier Ltd.)

Nanotechnology applications in medicine have seen a tremendous growth in the past decade and are being employed to enhance the stability and bioavailability of lipophilic substances, such as florfenicol. This study aimed to examine the pharmacokinetic properties of the formulated oil-in-water florfenicol-loaded nanoemulsion (FF-NE). FF-NE and florfenicol control (Nuflor) were administered to the pigs at a dose of 20 mg/kg. Nanoemulsion formulation of florfenicol was highly influenced in vivo plasma profile. The in vivo absorption study in pigs indicated that Cmax (14.54 μg/mL) was significantly higher in FF-NE, 3.42 times higher than the marketed formulation. In comparison with the control group, the relative bioavailability of formulated nanoemulsion was up to 134.5%. Assessment of bioequivalence using log-transformed data showed that the 90% confidence intervals (90% CI) of Cmax and AUC₀-∞ were 2.48-4.60 and 1.21-1.72, respectively., (© 2015 John Wiley & Sons Ltd.)

Background: Because psychological approaches are likely to produce sustained benefits without the risk for tolerance or adverse effects associated with pharmacologic approaches, cognitive behavioral therapy for insomnia (CBT-i) is now commonly recommended as first-line treatment for chronic insomnia., Purpose: To determine the efficacy of CBT-i on diary measures of overnight sleep in adults with chronic insomnia., Data Sources: Searches of MEDLINE, EMBASE, PsycINFO, CINAHL, the Cochrane Library, and PubMed Clinical Queries from inception to 31 March 2015, supplemented with manual screening., Study Selection: Randomized, controlled trials assessing the efficacy of face-to-face, multimodal CBT-i compared with inactive comparators on overnight sleep in adults with chronic insomnia. Studies of insomnia comorbid with medical, sleep, or psychiatric disorders were excluded., Data Extraction: Study characteristics, quality, and data were assessed independently by 2 reviewers. Main outcome measures were sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%)., Data Synthesis: Among 292 citations and 91 full-text articles reviewed, 20 studies (1162 participants [64% female; mean age, 56 years]) were included. Approaches to CBT-i incorporated at least 3 of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the posttreatment time point, SOL improved by 19.03 (95% CI, 14.12 to 23.93) minutes, WASO improved by 26.00 (CI, 15.48 to 36.52) minutes, TST improved by 7.61 (CI, -0.51 to 15.74) minutes, and SE% improved by 9.91% (CI, 8.09% to 11.73%). Changes seemed to be sustained at later time points. No adverse outcomes were reported., Limitation: Narrow inclusion criteria limited applicability to patients with comorbid insomnia and other sleep problems, and accuracy of estimates at later time points was less clear., Conclusion: CBT-i is an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes., Primary Funding Source: None. (PROSPERO registration number: CRD42012002863).

The collapsin response mediator protein 5 (CRMP-5) autoantibody is one of only several paraneoplastic antibodies associated with autonomic neuropathy. Such paraneoplastic neuropathies manifest with a constellation of autonomic abnormalities. We present a unique case of orthostatic hypotension as the sole feature of a CRMP-5 paraneoplastic autonomic neuropathy in a patient with small cell lung cancer. Given the poor prognosis of paraneoplastic autonomic dysfunction, it is important to accurately diagnose the cause of orthostatic hypotension occurring on a background of malignancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Transcatheter closure of coronary arterial fistula (CAF) is being utilized increasingly as an alternative to surgical closure, but most of the literature on transcatheter closure of CAF in children and adolescents consists of case reports and reports of small series. The aim of this study was therefore to describe our experience of percutaneous closure of CAF in children and adolescents., Methods: Between April 1998 and December 2012, 37 children and adolescents with congenital CAF underwent percutaneous transcatheter closure. After aortic root angiography and selective coronary angiography, a guidewire was positioned to the fistula. In some cases, an arteriovenous wire loop (AV loop) was created. The sheath passed along the wire to the site of the desired occlusion of the fistula. One or more occlusion devices were selected to embolize the fistula., Results: Occlusion devices were placed in 33 procedures (32 patients). Occlusion was unsuccessful in five patients. Duct occluders were placed in 12 procedures, coils in 11 (10 patients), muscular ventricular septal occluders in six, and vascular plugs in four procedures. The tricuspid valve was injured in two patients. One patient with a giant CAF aneurysm had a thrombosis within the aneurysm after transcatheter closure. There were no deaths, fistula dissection or myocardial infarction., Conclusion: Transcatheter closure of CAF is feasible in anatomically suitable cases, but injury to the tricuspid valve involved with AV loop methods can occur in closure procedures, and thrombus formation is possible in the blind pouch of the residual fistula after closure. Long-term follow up after fistula closure is necessary., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)

The title compound, {[Co(H(2)O)(6)][Co(SO(4))(C(10)H(8)N(2))(H(2)O)(3)][Co(SO(4))(2)(C(10)H(8)N(2))(H(2)O)(2)]}(n), contains three crystallographically unique Co(II) centres, all of which are in six-coordinated environments. One Co(II) centre is coordinated by two bridging 4,4'-bipyridine (4,4'-bipy) ligands, one sulfate ion and three aqua ligands. The second Co(II) centre is surrounded by two N atoms of two 4,4'-bipy ligands and four O atoms, i.e. two O atoms from two monodentate sulfate ions and two from water molecules. The third Co(II) centre forms part of a hexaaquacobalt(II) ion. In the crystal structure, there are two different one-dimensional chains, one being anionic and the other neutral, and adjacent chains are arranged in a cross-like fashion around the mid-point of the 4,4'-bipy ligands. The structure features O-H···O hydrogen-bonding interactions between sulfate anions and water molecules, resulting in a three-dimensional supramolecular network.

Objective: To report the results of transcatheter interventional therapy (TIT) of congenital heart disease (CHD) register from 23 medical centers in China., Method: In this retrospective multicenter registry study, clinical data from 5808 patients who underwent TIT between January 2008 to December 2010 in 23 Chinese medical centers in 14 cities were analyzed., Results: Procedure was successful in 5720 cases (98.5%), success rate was 99.5% for PDA, 98.8% for ASD, 97.4% for VSD and 98.5% for pulmonary stenosis (PS). Multivariate regression analysis showed that PDA size and procedure time, age and procedure time, distance from VSD to AV were significantly associated with the procedure success rate of PDA, ASD and VSD closure, respectively. Early complications occurred in 306 cases (5.3%), 36 cases (0.6%) experienced major complications including device embolization in 7 cases, serious aorta regurgitation in 5 cases, serious tricuspid regurgitation in 4 cases, tricuspid stenosis in 2 cases, heart block (HB) in 13 cases (2 in ASD and 11 in VSD), cardiac tamponade in 2 cases (1 ASD and 1 PS) and hemolysis in 3 cases. Procedure time and PDA size, ASD size, device size, age and PS degree were risk factors related to the occurrence of the early complications for PDA, ASD and VSD closure and PBPV respectively. The median follow-up time was 15 months (range 1-36 months). The complete closure rate during follow up was 100% for ASD, PDA and VSD and the pressure gradient in PS decreased to normal range in all PS patients. Late complications occurred in 15 cases (0.2%), of which 3 cases needed surgery intervention and permanent pacemaker was implanted in 1 patient. There was no death during procedure and at follow-up period., Conclusions: TIT of CHD offers encouraging results in China. Follow up is warranted to monitor the occurrence of serious complications, especially late complications.

In the title compound, [Ni(C(12)H(8)N(2))(3)](C(10)H(5)O(8))(2)·H(2)O, the Ni(II) cation is coordinated by six N atoms of the three bidentate chelating 1,10-phenanthroline ligands in a slightly distorted octa-hedral coordination geometry. The Ni-N bond lengths range from 2.074 (2) to 2.094 (2) Å. The dihedral angles between the three chelating NCCN groups to each other are 85.71 (3), 73.75 (2) and 85.71 (3)°, respectively. The Ni cation, the phenyl ring of the 1,10-phenanthroline ligand and the lattice water molecule are located on special positions (site symmetry 2). In the crystal, the uncoordinated 2,4,5-tricarb-oxy-benzeno-ate anions join with each other through O-H⋯O hydrogen bonds, forming a two-dimensional hydrogen-bonded layer structure along the bc plane. The layers are further linked via additional O-H⋯O inter-actions between water and carboxyl groups, resulting in a three-dimensional supra-molecular network.

Objective: To retrospectively summarize the effect of non-medical therapies for pediatric patients with hypertrophic obstructive cardiomyopathy (HOCM)., Methods: From Nov. 2008 to Jun. 2010, 4 children with drug-refractory HOCM were admitted to our hospital. Their ages were 14, 7, 9 and 6 years old, respectively. Their body weights were 38, 17, 21.5 and 17 kg, respectively. Before operation, the pressure gradients over left ventricular outflow tract (LVOTG) were 60, 147, 58 and 114 mm Hg (1 mm Hg = 0.133 kPa), respectively. And mitral regurgitation (MR) areas were 2.2, 7.3 cm(2) and 2.9 cm(2), respectively, except that it was trivial in one case. Percutaneous transluminal septal myocardial ablation (PTSMA) was performed in case 1 and 2. Septal myectomy (SM) was performed in case 3 and 4. Follow-up was first performed right after operation or before discharge, then 1 month, 3 months, 6 months, and 12 months after operation, and then once a year. The follow-up period was 1 - 18 (9.3 ± 8.1) months., Results: All patients experienced relieved symptoms. Three of them had their NYHA functional class improved except case 2. Echocardiography revealed that LVOTGs right after operations were 38, 79, 20 and 0 mm Hg, respectively, suggesting significant improvement of left ventricular outflow tract obstruction (LVOTO) in all patients. During follow-up, case 2 suffered from recurrence of LVOTO, while the other 3 cases showed sustained relief. In the last follow-up, the LVOTGs of the four patients were 19, 168, 16 and 0 mm Hg, respectively. Echocardiography also revealed that MRs of all patients were significantly reduced, even in case 2 whose LVOTG rebounded, with no recurrence during follow-up. Severe complications were absent, such as ventricular septum perforation, cardiac tamponade, ventricular tachycardia or ventricular fibrillation. No one suffered from complete heart block. Transient complete right bundle branch block (CRBBB) was observed in case 1 after PTSMA and converted to intraventricular block after 1 month. Complete left bundle branch block (CLBBB) was present in both case 3 and 4, who received SM. In case 4, it converted to intraventricular block after 1 month while in case 3 CLBBB persisted., Conclusions: The initial experience showed that PTSMA and SM were safe and effective for drug-refractory symptomatic HOCM children, with satisfactory short-term results. Further studies are needed to evaluate the long-term results and complications.

Background and Aim: Western countries are seeing an increasing prevalence of chronic viral hepatitis and a subsequent rise in the incidence of hepatocellular carcinoma (HCC). Screening patients at high risk of HCC has become standard practice. The aim of this study was to assess the efficacy and cost of screening high-risk individuals for HCC in an Australian tertiary hospital., Methods: A retrospective review was performed of all patients who underwent HCC screening at the Austin Hospital in Melbourne between 1 October 1998 and 31 August 2004. HCC screening was carried out in all cirrhotic patients and male non-cirrhotic patients with chronic hepatitis B virus. Screening consisted of 6-monthly alpha fetoprotein (AFP) measurements and ultrasounds (US). Outcomes of those who had HCC detected were followed up until 15 February 2007. Patients who had HCC satisfying the Milan criteria for liver transplantation were considered to have potentially curable tumor. Costs for the diagnostic tests were obtained from the 2004 Australian Medicare Benefits Schedule., Results: A total of 268 patient records were reviewed as part of the study. Chronic viral hepatitis accounted for 63% of the patients (n = 167). US screening was carried out at a median of 6.5 months and AFP measurements at a median of 4.0 months. HCC was detected in 22 patients (8.2%) at an incidence of 2.7% per year. These patients had a mean follow up of approximately 5.0 years after tumor detection. At the time of diagnosis, 17 patients had potentially curable tumor and 10 were alive at the conclusion of follow up. Of these 10 patients, six were successfully transplanted, three were successfully treated with radiological therapies and one was awaiting transplantation. The total cost of the screening program over the study period, including secondary investigations, was $A300,568. The cost per HCC detected was $13,662 and cost per potentially curable HCC was $17,680., Conclusion: An effective HCC screening program can be provided through a multi-disciplinary outpatient facility in an Australian teaching hospital. Further stratification of the high risk patient cohort may improve the cost effectiveness of this screening program.

Objective: To evaluate the efficacy of interventional therapy for complex congenital heart defects patients with un-repaired or postoperative residual lesions., Methods: Between March 1998 and April 2009, 42 patients (12 females), mean age 6 years (5 months to 30 years) received interventional therapy, 17 cases underwent occlusion of major aorto-pulmonary collateral arteries (MAPCAs), 15 underwent device closure of residual ventricular or atrial septal shunting, 12 underwent balloon angioplasty (n = 10) and stenting (n = 2) for stenosis of the anastomosis of vessels or branched pulmonary arteries., Results: Twenty-three MAPCAs were performed in 17 patients without residual shunting. One patient died of multiple organ failure after intervention therapy and the remaining patients discharged without complication, successful device closure was performed in 15 patients and there was minimal residual shunting in 1 patient. There were no severe arrhythmias such as complete atrio-ventricular block during and post procedure. Exercise capacities were significantly improved in 12 patients underwent balloon angioplasty or stenting. Pressure gradients were significantly decreased and there was no aneurysmal or thromboembolic formation post procedure., Conclusions: Interventional therapy is a safe and effective therapy option for treating complex congenital heart defects patients with un-repaired or postoperative residual lesions.

Objective: To summarize the experience in diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in children., Methods: A total of 14 children (7 females and 7 males) with ARVC were involved. The cases underwent electrocardiography, echocardiography, cardiac CT or MRI examinations. All cases were treated with sotalol or amiodarone in combination with propranolol. In 2 cases with drug-refractory ventricular extrasystoles, catheter ablation treatment was performed. In 6 cases with obvious impaired ventricular function, additional pharmacological therapy including vasodilators, diuretics, and digitalis were given., Results: Ventricular extrasystoles occurred in all 14 cases and ventricular tachycardia in 8 cases. Ten cases showed Epsilon wave on electrocardiography. All 14 cases had enlarged right ventricle and reduced right ventricular ejection fraction. CT or MRI examination showed right ventricular dilatation and a thinned wall of right ventricle in 10 cases. Ventricular extrasystoles or tachycardia disappeared in 7 cases and was reduced in 4 cases after treatment. The two children receiving catheter ablation treatment did not present ventricular extrasystoles or tachycardia in a 3-month follow-up. The heart function was improved in the 6 children with obvious impaired ventricular function after pharmacological therapy., Conclusions: The clinical manifestations are diverse in children with ARVC. A definite diagnosis of ARVC should be based on a combination of electrocardiography and echocardiography examinations. Pharmacological therapy is effective partially. Catheter ablation treatment appears to be a promising option in patients with drug-refractory ventricular extrasystoles.

The objective of this study was to investigate the possible association of the ABCB1 gene C3435 T polymorphism and the CYP3A5 gene A6986G polymorphism with sirolimus (SRL) trough concentration and dose requirements in Chinese stable renal transplant recipients. Blood samples were collected from 105 healthy volunteers and 50 renal transplant patients, whose polymorphisms of the ABCB1 and CYP3A5 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Plasma concentrations of SRL were determined with HPLC. The allele frequencies of the ABCB1 mutation in Chinese healthy volunteers and renal transplant recipients were 51.0% and 44.0% (p>0.05), while the allele frequencies of the CYP3A5 mutation were 72.9% and 71.0% (p>0.05). The SRL concentration/dose ratio (C/D) in patients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (p<0.05). However, no significant differences were observed between C/D and ABCB1 SNPs (p>0.05). These results confirm that when treated with a SRL-based therapy and low-dose steroids, patients carrying the CYP3A5(*)1 allele required significantly more SRL to achieve adequate blood trough concentrations. In patients with SRL-based therapy, genotyping of the CYP3A5 genes may help to optimize the SRL management in renal transplant recipients., (2007 John Wiley & Sons, Ltd)

Objective: To evaluate the early complications during and after transcatheter closure of perimembranous ventricular septal defects (PMVSDs) in children., Methods: A total of 223 patients received transcatheter closure of PMVSDs from March 2002 to December 2005 in our hospital were included in this retrospective study., Results: The overall complications rate was 26.9% (60/223). Major complications occurred in 9 patients (4.0%) including III degrees atrioventricular block (AVB) in 2 (0.9%), hemolysis in 3 (1.3%) and surgical interventions in 4 patients (1.8%) because of device malposition (1), mild aortic regurgitation (2) and device embolization (1) and all 4 patients recovered without further complications. The 2 patients with III degrees AVB were completely recovered to normal sinus rhythm after 7 days treatment with temporary pacemaker and corticosteroid. Hemolysis in 3 patients disappeared after corticosteroid treatment. Minor complications occurred in 51 patients (22.8%) including bundle branch block (BBB) in 37 (16.6%), first-degree AVB in 2 (0.9%), second-degree AVB in 1 (0.4%), new-onset mild aortic regurgitation in 5 (2.2%) and new-onset mild to moderate tricuspid regurgitation in 6 patients (2.6%). Except for right bundle branch blocks, other BBBs were treated with albumin and corticosteroid and completely recovered. No treatment was applied for new-onset valve regurgitations. There was no death in all 223 patients., Conclusions: Early complications post PMVSDs in children are mostly minor with good prognosis and the prognosis for major complications post PMVSDs is good after proper treatment.

Objective: To investigate the abnormal abundances of calcium regulatory proteins in rabbit myocytes with failing hearts., Methods: Sixteen rabbits were divided into two groups: 8 rabbits with heart failure induced by volume plus pressure overload and 8 sham-operated animals. The hemodynamic parameters and cardiac structure and function were detected via catheterization and echocardiography respectively. L-type calcium channel (LTCC), Ryanodine receptor 2 (RyR2), Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), and Na(+)-Ca(2+) exchanger (NCX) protein abundances were determined by Western blot analysis., Results: The ratio of left ventricular mass to body weight, heart rate and left ventricular end diastolic pressure in heart failure rabbits were significantly increased compared with sham-operated rabbits (P < 0.01), but their left ventricular shorten fraction [(21.3 +/- 4.00)% vs. (36.5 +/- 1.36)%] and ejection fraction (0.45 +/- 0.07 vs. 0.70 +/- 0.02) were decreased (P < 0.01). In heart failure rabbits, the abundances of LTCC and RyR2 were significantly decreased (R(LTCC/actin): 0.287 +/- 0.029 vs. 0.624 +/- 0.009; R(RyR2/actin): 0.106 +/- 0.001 vs. 0.203 +/- 0.011; P < 0.01), whereas the expressions of SERCA2a and NCX were markedly increased (R(NCX/actin): 0.497 +/- 0.015 vs. 0.221 +/- 0.014; R(SERCA2a/actin): 0.611 +/- 0.036 vs. 0.433 +/- 0.008; P < 0.01)., Conclusions: Reductions of LTCC and RyR2 might contribute to risk factors of systolic dysfunction in failing hearts. In early stage of heart failure, upregulated SERCA2a and NCX protein levels may be helpful for maintaining cardiac performance.

Objective: To discuss the treatment of arrhythmia occurs in the process of transcatheter closure of perimembranous ventricular septal defects (VSD) in pediatric patients., Methods: 182 cases (mean age: 6.2 +/- 3.3 years) with membranous VSD underwent transcatheter occlusion procedure. Two different devices were used: the Amplatzer membranous VSD occluder in 81 patients and the domestic-made device in 101 patients. Electrocardiogram of all patients was recorded before and during closure and at one day after the procedure, and Holter monitoring was performed one week after the procedure., Results: Perioperation arrhythmia occurred in thirty-one patients (17%). Second- or third-degree atrioventricular bundle (AVB) was noted during the procedure in four patients. Normal AV conduction recovered spontaneously before the catheters were withdrawn in three cases and another patient underwent surgical repair. In the other twenty-seven patients, arrhythmia was first documented between one day and one week after the procedure. Third-degree AVB was found in three (1.6%) children after the procedure and underwent the temporary pacemaker (TPM) was implanted, two of them recovered to normal sinus rhythm within one week, another patient underwent elective surgery to remove the occluder and repair the defect. Other arrhythmias were: left bundle-branch block (n = 3), right bundle-branch block (n = 12), second-degree AVB (n = 2), sinus tachycardia (n = 6)., Conclusions: In properly selected cases of perimembranous VSD, the transcatheter closure is safe and effective by using appropriate devices. During and after the procedure, closure of VSD can be associated with some kinds of arrhythmia, such as A-V block, more intensive observation and follow-up were therefore needed.

Objective: To document the five-year follow-up results of transcatheter Amplatzer duct occluder (ADO) occlusion of patent ductus arteriosus (PDA) in children and to assess the safety and effectiveness of this method for PDA closure., Methods: A retrospective cohort study was completed in patients with PDA underwent transcatheter closure by the ADO in Guangdong Cardiovascular Institute from April 1998 to December 2003., Results: Transcatheter closure of PDA with ADO was attempted in 250 children patients. The median age was 5.3 years and median weight was 15.1 kg. The PDAs were from 1.8 mm to 11.0 mm (median 4.2 mm) in the narrowest diameter, of which 52 were larger than 5 mm (20.0%). All PDAs were occluded with 4 approximately 14 mm ADO through 6F (n = 205) or 7F (n = 45) sheaths. Devices were successfully implanted in 245 patients (98.0%). The Qp/Qs decreased from 1.90 +/- 0.60 to 1.03 +/- 0.21 (P < 0.05). All shapes of the PDA could be closed. Late complication occurred in five patients, including hemolysis in three patients and the los of the pulse of femoral artery in two patients. Follow-up after device implantation was accomplished in 205 patients (82.0%). The incidence of residual shunt at follow-up periods of 1 d, 1 m, 6 m, 12 m, 24 m, 36 m, 48m and 60 m after device occlusion was 9.2%, 2.8%, 1.2%, 0.8%, 0, 0, 0 and 0, respectively. Five patients (2.0%) required re-intervention to treat residual shunt with or without hemolysis. Event-free rates were 98.0% at one year and five years., Conclusion: This long-term follow-up result confirmed the safety and effectiveness of ADO closure of PDAs in children.

Objective: To study the clinical technology of transcatheter closure of secundum atrial septal defects (ASD) with Amplatzer device in younger and lower body weight children., Methods: The transcatheter closure of ASD using Amplatzer septal occluder (ASO) was performed in 165 children under 5 years of age (75 boys and 90 girls) with secundum ASD from Aug 1998 to May 2004. The age of the cases ranged from 2 to 5 (mean 3.7 +/- 1.1) years. The body weight ranged from 9 to 18 (mean 12.6 +/- 2.3) kg. The ratio of pulmonary circulation quantity to the systemic circulation quantity (Qp/Qs) was 3.2 +/- 1.9. All the patients underwent clinical examination, X-ray, electrocardiography (ECG) and echocardiography (Echo) for diagnosis of secundum ASD. The transthoracic echocardiography (TTE) was used to detect and measure the defect of the patients and even trans-esophageal echocardiography (TEE) had to be used when it was necessary. With Echo and X-ray guidance, the measuring balloon was used in the body and outside the body to determine the balloon-stretch diameters of ASD, and proper occluders were selected accordingly for the patients for interventional treatment of ASD., Results: The devices were implanted successfully in 163 (98.8%) cases. One failure occurred in a case in whom the device moved into the left atrium after release, and the other failure was that the position of the device was uncertain because of temporary unavailability of a special transducer for TEE. Surgical operations were performed for these two cases. The stretch diameter of ASD was from (8 - 30) mm, (mean 18.3 +/- 5.1) mm. The size of device was selected according to the stretch diameter of ASD. The diameter of the occluders selected was from (8 - 30), (mean 18.6 +/- 5) mm in this series. The occlusion procedure was monitored by fluoroscopy and TTE and in 5 cases (3%) by TEE. The diameter of right ventricle was improved within 2 days after occlusion from (mean 16.4 +/- 4.9) mm to (mean 12.6 +/- 3.8) mm, (p < 0.01). One hundred and forty seven cases belonged to the simple secundum ASD(89%). Thirteen cases who were complicated with other cardiac deformity were treated successfully with different interventional procedure. Six cases had multiple openings and three of these cases had tumour-like changes of the atrial septum which were closed completely just by one occluder. In only one case small quantity of residual shunt remains. No other severe complication was found in this group. About 100 cases (60%) had large ASD, so the procedure was more difficult in those cases., Conclusion: The clinical effectiveness of treatment of ASD in children under 5 years of age with Amplatzer occluders was satisfactory and therefore this therapeutic procedure is feasible for this age group of patients. Nevertheless, we do not recommend to use the technique for infants and children under 2 years of age. Strict selection of indications and proper size of occluder and good cardiologic and surgical settings are among the basic factors for successful interventional occlusion of ASD in young children.

Aim: To study whether dietary intake influences liver function test., Methods: Blood samples were obtained from patients liver diseases (n = 100) and controls (without liver diseases; n = 100) first at 07: 00 in the morning (fasting state) and then 2 h after a meal (fed state). The Hitachi-7150 automatic biochemistry analyzer was used to assess the following liver function indexes: Serum bilirubin, thymol turbidity test, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transferase, SP, A and G. Statistical significance of differences between inter-group values was determined using SAS software., Results: None of the indexes showed statistically significant differences between the fasting state and the fed state (P = 0.476-0.978)., Conclusion: Liver function test can be performed after a meal.