Showing papers by "Feng Zhang published in 2008"

Mechanisms for human genomic rearrangements

Abstract: Genomic rearrangements describe gross DNA changes of the size ranging from a couple of hundred base pairs, the size of an average exon, to megabases (Mb). When greater than 3 to 5 Mb, such changes are usually visible microscopically by chromosome studies. Human diseases that result from genomic rearrangements have been called genomic disorders. Three major mechanisms have been proposed for genomic rearrangements in the human genome. Non-allelic homologous recombination (NAHR) is mostly mediated by low-copy repeats (LCRs) with recombination hotspots, gene conversion and apparent minimal efficient processing segments. NAHR accounts for most of the recurrent rearrangements: those that share a common size, show clustering of breakpoints, and recur in multiple individuals. Non-recurrent rearrangements are of different sizes in each patient, but may share a smallest region of overlap whose change in copy number may result in shared clinical features among different patients. LCRs do not mediate, but may stimulate non-recurrent events. Some rare NAHRs can also be mediated by highly homologous repetitive sequences (for example, Alu, LINE); these NAHRs account for some of the non-recurrent rearrangements. Other non-recurrent rearrangements can be explained by non-homologous end-joining (NHEJ) and the Fork Stalling and Template Switching (FoSTeS) models. These mechanisms occur both in germ cells, where the rearrangements can be associated with genomic disorders, and in somatic cells in which such genomic rearrangements can cause disorders such as cancer. NAHR, NHEJ and FoSTeS probably account for the majority of genomic rearrangements in our genome and the frequency distribution of the three at a given locus may partially reflect the genomic architecture in proximity to that locus. We provide a review of the current understanding of these three models.

Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri

Abstract: The introduction of two microbial opsin-based tools, channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to neuroscience has generated interest in fast, multimodal, cell type-specific neural circuit control. Here we describe a cation-conducting channelrhodopsin (VChR1) from Volvox carteri that can drive spiking at 589 nm, with excitation maximum red-shifted approximately 70 nm compared with ChR2. These results demonstrate fast photostimulation with yellow light, thereby defining a functionally distinct third category of microbial rhodopsin proteins.

Genome-wide Association Study Identifies Genes for Biomarkers of Cardiovascular Disease: Serum Urate and Dyslipidemia

Abstract: Many common diseases are accompanied by disturbances in biochemical traits. Identifying the genetic determinants could provide novel insights into disease mechanisms and reveal avenues for developing new therapies. Here, we report a genome-wide association analysis for commonly measured serum and urine biochemical traits. As part of the WTCCC, 500,000 SNPs genome wide were genotyped in 1955 hypertensive individuals characterized for 25 serum and urine biochemical traits. For each trait, we assessed association with individual SNPs, adjusting for age, sex, and BMI. Lipid measurements were further examined in a meta-analysis of genome-wide data from a type 2 diabetes scan. The most promising associations were examined in two epidemiological cohorts. We discovered association between serum urate and SLC2A9, a glucose transporter (p = 2 × 10−15) and confirmed this in two independent cohorts, GRAPHIC study (p = 9 × 10−15) and TwinsUK (p = 8 × 10−19). The odds ratio for hyperuricaemia (defined as urate >0.4 mMol/l) is 1.89 (95% CI = 1.36–2.61) per copy of common allele. We also replicated many genes previously associated with serum lipids and found previously recognized association between LDL levels and SNPs close to genes encoding PSRC1 and CELSR2 (p = 1 × 10−7). The common allele was associated with a 6% increase in nonfasting serum LDL. This region showed increased association in the meta-analysis (p = 4 × 10−14). This finding provides a potential biological mechanism for the recent association of this same allele of the same SNP with increased risk of coronary disease.

Schizophrenia-Related Neural and Behavioral Phenotypes in Transgenic Mice Expressing Truncated Disc1

Abstract: Disrupted-in-Schizophrenia-1 (DISC1), identified by positional cloning of a balanced translocation (1;11) with the breakpoint in intron 8 of a large Scottish pedigree, is associated with a range of neuropsychiatric disorders including schizophrenia. To model this mutation in mice, we have generated Disc1tr transgenic mice expressing 2 copies of truncated Disc1 encoding the first 8 exons using a bacterial artificial chromosome (BAC). With this partial simulation of the human situation, we have discovered a range of phenotypes including a series of novel features not previously reported. Disc1tr transgenic mice display enlarged lateral ventricles, reduced cerebral cortex, partial agenesis of the corpus callosum, and thinning of layers II/III with reduced neural proliferation at midneurogenesis. Parvalbumin GABAergic neurons are reduced in the hippocampus and medial prefrontal cortex, and displaced in the dorsolateral frontal cortex. In culture, transgenic neurons grow fewer and shorter neurites. Behaviorally, transgenic mice exhibit increased immobility and reduced vocalization in depression-related tests, and impairment in conditioning of latent inhibition. These abnormalities in Disc1tr transgenic mice are consistent with findings in severe schizophrenia.

Improved expression of halorhodopsin for light-induced silencing of neuronal activity.

Abstract: The ability to control and manipulate neuronal activity within an intact mammalian brain is of key importance for mapping functional connectivity and for dissecting the neural circuitry underlying behaviors. We have previously generated transgenic mice that express channelrhodopsin-2 for light-induced activation of neurons and mapping of neural circuits. Here we describe transgenic mice that express halorhodopsin (NpHR), a light-driven chloride pump that can be used to silence neuronal activity via light. Using the Thy-1 promoter to target NpHR expression to neurons, we found that neurons in these mice expressed high levels of NpHR-YFP and that illumination of cortical pyramidal neurons expressing NpHR-YFP led to rapid, reversible photoinhibition of action potential firing in these cells. However, NpHR-YFP expression led to the formation of numerous intracellular blebs, which may disrupt neuronal function. Labeling of various subcellular markers indicated that the blebs arise from retention of NpHR-YFP in the endoplasmic reticulum. By improving the signal peptide sequence and adding an ER export signal to NpHR-YFP, we eliminated the formation of blebs and dramatically increased the membrane expression of NpHR-YFP. Thus, the improved version of NpHR should serve as an excellent tool for neuronal silencing in vitro and in vivo.

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations

Abstract: The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario. In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations. We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.

Genome-wide Association Scan Identifies a Prostaglandin-Endoperoxide Synthase 2 Variant Involved in Risk of Knee Osteoarthritis

Abstract: Osteoarthritis (OA), the most prevalent form of arthritis in the elderly, is characterized by the degradation of articular cartilage and has a strong genetic component. Our aim was to identify genetic variants involved in risk of knee OA in women. A pooled genome-wide association scan with the Illumina550 Duo array was performed in 255 controls and 387 cases. Twenty-eight variants with p < 1 x 10(-5) were estimated to have probabilities of being false positives

System for Optical Stimulation of Target Cells

Abstract: Various systems and methods are implemented for controlling stimulus of a cell. One such method is implemented for optical stimulation of a cell expressing a NpHR ion pump. The method includes the step of providing a sequence of stimuli to the cell. Each stimulus increases the probability of depolarization events occurring in the cell. Light is provided to the cell to activate the expressed NpHR ion pump, thereby decreasing the probability of depolarization events occurring in the cell.

Optical tissue interface method and apparatus for stimulating cells

Abstract: In one example, a system electrically stimulates target cells of a living animal using an elongated structure, a modulation circuit and a light pathway such as provided by an optical fiber arrangement. The elongated structure is for insertion into a narrow passageway in the animal such that an end of the elongated structure is sufficiently near the target cells to deliver stimulation thereto. The modulation circuit is for modulating the target cells while the elongated structure is in the narrow passageway, where the modulation circuit is adapted to deliver viral vectors through the elongated structure for expressing light responsive proteins in the target cells. The light pathway is used for stimulating the target cells by delivering light to the light-responsive proteins in the target cells.

Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function

Abstract: Background: Regeneration of the myocardium and improved ventricular function have been demonstrated in patients with acute myocardial infarction (MI) treated by intracoronary delivery of autologous bone marrow mononuclear cells (BMC) a few days after successful myocardial reperfusion by percutaneous coronary intervention (PCI); however, the effects of intracoronary cell infusion in chronic MI patients are still unknown. Aims: To investigate whether intracoronary infusion of BMC into the infarct-related artery in patients with healed MI could lead to improvement in left ventricular (LV) function. Methods: Among 47 patients with stable ischaemic heart disease due to a previous MI (13 (SD 8) months previously), 24 were randomised to intracoronary infusion of BMC (BMC group) and 23 to a saline infusion (control group) into the target vessel after successful PCI within 12 hours after chest pain occurred. LV systolic and diastolic function, infarct size and myocardial perfusion defect were assessed with the use of echocardiography, magnetic resonance imaging (MRI) or 201 Tl single-photonemission computed tomography (SPECT) at baseline and repeated at the 6-month follow-up examination. Results: BMC treatment did not result in a significant increase in LV ejection fraction in any of the groups by any of the methods used, and the apparent tendency of an improvement was not statistically different between the two groups. The two groups also did not differ significantly in changes of LV end-diastolic and systolic volume, infarct size or myocardial perfusion. However, there was an overall effect of BMC transfer compared with the control group with respect to early/late (E/A) (p,0.001), early diastolic velocity/late diastolic (Aa) velocity (Ea/Aa) ratio (p = 0.002) and isovolumetric relaxation time (p = 0.038) after 6 months, as evaluated by tissue Doppler echocardiography. We noted no complications associated with BMS transfer. Conclusion: Intracoronary transfer of autologous BMC in patients with healed MI did not lead to significant improvement of cardiac systolic function, infarct size or myocardial perfusion, but did lead to improvement in diastolic function.

Fabrication of One-Dimensional Iron Oxide/Silica Nanostructures with High Magnetic Sensitivity by Dipole-Directed Self-Assembly

Abstract: Weakly ferromagnetic iron oxide nanoparticles with narrow size distribution were prepared by a high-temperature hydrolysis reaction. The magnetic nanoparticles can self-assemble into one-dimensional particle chains on substrates as well as in colloid dispersion through magnetic dipolar interaction without the help of an applied magnetic field. The 1D assemblies were further harnessed to prepare 1D nanostructures with aligned magnetic nanoparticle inclusions and a continuous silica shell. One-dimensional iron oxide/silica nanostructures were prepared through chainlike self-assembly of the magnetic nanoparticles in a mixture of ethanol, ammonia, and water followed by a sol−gel process of TEOS at the surface of the assemblies. The length of the nanostructures can be controlled by the amplitude of ultrasonication, and the thickness of the silica coating can be tuned by the dosage of TEOS. The 1D nanostructures exhibit highly magnetic sensitivity. In the presence of an applied magnetic field, the nanostructure...

Dentine bond strength and microleakage of flowable composite, compomer and glass ionomer cement.

Abstract: Background: To assess in vitro the dentine bond strength and microleakage of three Class V restorations viz. flowable composite, compomer and glass ionomer cement. Methods: Eighteen dentine specimens were prepared and randomly distributed among three groups. Three kinds of restoration materials were each bonded on prepared dentine surfaces in three groups as per the manufacturers’ instructions. Group Aelite: Tyrian SPE (a no-rinse, self-priming etchant) + One Step Plus (an universal dental adhesive) + Aeliteflo (a flowable composite); Group Dyract: Prime & Bond NT (a no-rinse, self-priming dental adhesive) + Dyract AP (a compomer); Group GlasIonomer: GlasIonomer Type II (a self-cured restorative glass ionomer). Fifteen dentine/restoration microtensile bond test specimens were prepared from each group and were subjected to microtensile bond strength testing. The bond interfaces were observed morphologically using a scanning electron microscope (SEM). Twenty-four cervical cavities of 4.0 mm mesiodistal length, 2.0 mm occlusogingival height and 1.5 mm depth were prepared at the cemento-enamel junction (CEJ) on both buccal and lingual surfaces of each tooth. The cavities were each filled with flowable composite (Group Aelite), compomer (Group Dyract) and glass ionomer cement (Group GlasIonomer) using the same material and methods as for the microtensile bond tests. Microleakage of each restoration was evaluated by the ratio of the length of methylene blue penetration along the tooth-restoration interface and the total length of the dentine cavity wall on the cut surface. Results: One-way ANOVA and least significant difference (LSD) tests revealed statistically significant differences among the dentine bond strength for Group Aelite (28.4 MPa), Group Dyract (15.1 MPa) and Group GlasIonomer (2.5 MPa). SEM images showed intimate adaptation in the restoration/dentine interfaces of Group Aelite and Group Dyract. All of the systems tested in this study presented microleakage. However, both Group Aelite (0.808) and Group Dyract (0.863) had significantly less microleakage than Group GlasIonomer (0.964). There were no statistically significant microleakage differences between Group Aelite and Group Dyract, and no statistically significant microleakage differences between the occlusal margin and gingival margin. Conclusions: None of the systems tested in this study completely eliminated microleakage. However, both the flowable composite and compomer provided stronger dentine bond strengths and better margin sealing than the conventional glass ionomer cement. Occlusal forces exerted the same effects on microleakage of the occlusal margin and gingival margin in cervical cavities.

A frequent partial AZFc deletion does not render an increased risk of spermatogenic impairment in East Asians.

Abstract: Summary The gene families in the AZFc region of the Y chromosome have been shown to be functionally important in human spermatogenesis. The gr/gr deletion, a partial AZFc deletion that reduces the copy numbers of all the AZFc gene families, was identified as a significant risk factor for spermatogenic impairment in Dutch, Spanish and Italians. However, the presence of this deletion in healthy French and Germans questioned its importance in male infertility. In this study, we have shown that the gr/gr deletion does not render an increased risk in Han Chinese. In fact, the gr/gr deletion is frequent (about 8%) in our survey of 886 East Asians from 8 ethnic groups. Furthermore, the DAZ1/DAZ2 deletion has been detected as the primary subtype of the gr/gr deletion in East Asians, though this doublet has been considered as crucial for normal spermatogenesis in Europeans. The different spermatogenic effects of various types of the partial AZFc deletion suggest that the functional difference between AZFc gene copies is a likely cause of inconsistent associations of the gr/gr deletion with spermatogenic impairment across populations.

A spatial analysis of genetic structure of human populations in China reveals distinct difference between maternal and paternal lineages.

Abstract: Analyses of archeological, anatomical, linguistic, and genetic data suggested consistently the presence of a significant boundary between the populations of north and south in China. However, the exact location and the strength of this boundary have remained controversial. In this study, we systematically explored the spatial genetic structure and the boundary of north-south division of human populations using mtDNA data in 91 populations and Y-chromosome data in 143 populations. Our results highlight a distinct difference between spatial genetic structures of maternal and paternal lineages. A substantial genetic differentiation between northern and southern populations is the characteristic of maternal structure, with a significant uninterrupted genetic boundary extending approximately along the Huai River and Qin Mountains north to Yangtze River. On the paternal side, however, no obvious genetic differentiation between northern and southern populations is revealed.

Comparison of Population-Based Association Study Methods Correcting for Population Stratification

Abstract: Population stratification can cause spurious associations in population–based association studies. Several statistical methods have been proposed to reduce the impact of population stratification on population–based association studies. We simulated a set of stratified populations based on the real haplotype data from the HapMap ENCODE project, and compared the relative power, type I error rates, accuracy and positive prediction value of four prevailing population–based association study methods: traditional case-control tests, structured association (SA), genomic control (GC) and principal components analysis (PCA) under various population stratification levels. Additionally, we evaluated the effects of sample sizes and frequencies of disease susceptible allele on the performance of the four analytical methods in the presence of population stratification. We found that the performance of PCA was very stable under various scenarios. Our comparison results suggest that SA and PCA have comparable performance, if sufficient ancestral informative markers are used in SA analysis. GC appeared to be strongly conservative in significantly stratified populations. It may be better to apply GC in the stratified populations with low stratification level. Our study intends to provide a practical guideline for researchers to select proper study methods and make appropriate inference of the results in population-based association studies.

Myocardial bridging detection by non-invasive multislice spiral computed tomography: comparison with intravascular ultrasound.

Abstract: BACKGROUND Invasive intravascular ultrasound (IVUS) is current diagnostic standard for myocardial bridging (MB) Non-invasive multislice computerized tomography coronary angiography (MSCT) technique has provided a good anatomical view of the tunnel artery now METHODS A total of 51 consecutive patients with atypical or typical angina scheduled for IVUS were enrolled in this study and MSCT was performed 7 days before IVUS Coronary imaging was quantified using IVUS and MSCT Four main vessels (left main artery (LMA), left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA)) were examined RESULTS Forty-one out of 51 (80%) patients received metaprolol (25 mg) before the MSCT scan and 25 of them were current beta-blocker users The mean heart rate was (64 +/- 3) beats per minute A total of 51 patients underwent IVUS examination (30 with MB and 21 without MB) were chosen for this study Twenty-eight out of 30 MB cases were correctly diagnosed by MSCT and 2 patients with MB were not detected Comparison with IVUS, the sensitivity of detection by MSCT was 93%, specificity was 100% The lumen diameter of the tunnel artery derived from MSCT and IVUS significantly decreased from (29 +/- 03) mm to (24 +/- 04) mm (P < 0001) and from (33 +/- 03) mm to (26 +/- 05) mm (P < 0001), respectively Minimal and maximal diameters of MB derived from MSCT were significantly smaller than those from IVUS ((24 +/- 04) mm vs (26 +/- 05) mm, P < 005 and (29 +/- 03) mm vs (33 +/- 03) mm, P < 005), respectively CONCLUSIONS MSCT offers a reliable non-invasive method for MB in LAD and atherosclerosis diagnosis with diagnostic accuracy comparable with invasive IVUS

A whole genome linkage scan for QTLs underlying peak bone mineral density.

Abstract: We conducted a whole genome linkage scan for quantitative trait loci (QTLs) underlying peak bone mineral density (PBMD). Our efforts identified several potential genomic regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation. Peak bone mineral density (PBMD) is an important clinical risk predictor of osteoporosis and explains a large part of bone mineral density (BMD) variation. To detect susceptive quantitative trait loci (QTLs) for PBMD variation including consideration of epistatic and sex-specific effects, we conducted a whole genome linkage scan (WGLS) for PBMD using 2,200 Caucasians from 207 pedigrees, aged 20–50 years. All the individuals were genotyped with 410 microsatellite markers. In addition to WGLS in the total combined sample of males and females, we conducted epistatic interaction analyses, and sex-specific subgroup linkage analyses. We identified several potential genomic regions that met the criteria for suggestive linkage. The most impressing region is 12p12 for hip PBMD (LOD = 2.79) in the total sample. Epistatic interaction analyses found a significant epistatic interaction between 12p12 and 22q13 (p = 0.0021) for hip PBMD. Additionally, we detected suggestive linkage evidence at 15q26 (LOD = 2.93), 2p13 (LOD = 2.64), and Xq27 (LOD = 2.64). Sex-specific analyses suggested the presence of sex-specific QTLs for PBMD variation. Our efforts identified several potential regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.

Controlling Neuronal Activity

Abstract: With a new technology called optogenetics, it is possible to turn neuronal activity on and off in distinct neuronal populations, using cell-type specific, optically-sensitive, molecular, neuronal activity "switches." These "switches" are microbial, light-sensitive ion conductance-regulating proteins, exemplified by channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR). They are individually introduced into neuronal populations in the brain and become part of the cellular machinery. Ion flux-regulating activity of these “switches” can be controlled externally with light pulses. ChR2 is a cation channel that allows sodium ions to pass into a neuron after it has been activated by approximately 470 nm blue light (thereby increasing activity of the neuron and increasing action potentials). NpHR is a chloride pump that transfers chloride anions into the neuron after it has been activated by approximately 580 nm yellow light (thereby increasing accumulation of negative charge inside the cell and suppressing activity of the neuron). For application of this technology, light of the proper wavelength is delivered to the brain region of interest using a fiberoptic-based system or a light-emitting diode (LED). ChR2 and NpHR can be controlled independently to either increase action-potential firing of specific target neurons or to suppress neural activity, respectively, in intact tissue. In animal experiments, the LED or fiberoptic can be tethered to an external power source with lightweight flexible connectors, allowing stimulation during normal, freely moving behavior. The genes encoding these proteins are introduced into the brain with viral vectors and are expressed in distinct populations of neurons in vivo using specific DNA promoters fused to the gene, thereby guiding expression only in the cell type of choice.

The clinical spectrum associated with a chromosome 17 short arm proximal duplication (dup 17p11.2) in three patients.

Abstract: The p11.2-p12 region of human chromosome 17 is gene rich and composed of at least two genomically unstable domains: the Smith-Magenis syndrome region (17p11.2) and the Charcot-Marie-Tooth region (17p12), both of which are flanked by several low-copy repeat sequences. Homologous recombination between these flanking repeats results in either deletion- or duplication-associated phenotypes caused by a gene dosage effect. We report on the clinical phenotype of three patients presenting with either a 17p11.2 or 17p11.2p12 duplication, revealed by chromosome analysis and confirmed by fluorescent in situ hybridization analysis, high resolution genomic analysis of the 17p region using oligonucleotide array comparative genomic hybridization, and molecular studies with microsatellite markers. Two patients carry the 17p11.2 duplication, while the third one shows a larger duplication including the 17p12 region. The facial features observed in our patients include triangular face, full cheeks, smooth philtrum, thin upper lip, dental malocclusion, irregular eyebrows, and sparse hair, all of which are consistent with the pure proximal dup 17p phenotype. The patients' other clinical features are compared with previously published cases.

A more than 2-year follow-up of incomplete apposition after drug-eluting stent implantation.

Abstract: Background Incomplete stent apposition (ISA) has been demonstrated to be more common after drug-eluting stent (DES) implantation than after bare metal stent (BMS) implantation. Clinical outcomes of ISA remain controversial and the predictive accuracy of previous studies was limited by the short follow-up period of only 12-18 months. In the present study, we present the outcomes of a more than 2-year follow-up in patients with ISA after DES implantation. Methods From the clinical and core intravascular ultrasound (IVUS) database of the hospital, we identified 76 patients who had undergone DES implantation in de novo lesions between January 2004 and June 2005 and had received IVUS examination at a scheduled 6-month follow-up. A total of 13 (17.1%) patients had documented ISA at the follow-up by IVUS. Clinical follow-up was available up to 41 months after DES implantation and up to 33 months after identification of ISA. Results Over a mean follow-up of (34+/-5) months (range 24-41 months), 3 of the 13 patients (23.1%) suffered from ST elevated myocardial infarction with one death. Angiography confirmed the very late stent thrombosis (ST) in the area with ISA. All the 3 patients were implanted with sirolimus eluting stents in left anterior descending artery (LAD) and the very late ST occurred at 29, 31 and 32 months after DES implantation, and separately at 20, 23 and 23 months after the identification of ISA. All of the 3 patients had antiplatelet therapy continued before suffering from ST, and had been apparently stable on antiplatelet monotherapy with aspirin for a long period following dual antiplatelet therapy with aspirin and clopidogrel for more than 12 months. Conclusion ISA of DES may be associated with a high incidence of very late stent thrombosis, even in clinically stable patients with dual antiplatelet therapy of at least 12 months after the procedure.

HAPSIMU: a genetic simulation platform for population-based association studies

Abstract: Background Population structure is an important cause leading to inconsistent results in population-based association studies (PBAS) of human diseases. Various statistical methods have been proposed to reduce the negative impact of population structure on PBAS. Due to lack of structural information in real populations, it is difficult to evaluate the impact of population structure on PBAS in real populations.

Liver Transplantation for Erythropoietic Protoporphyria With Hepatic Failure: A Case Report

Abstract: Erythropoietic protoporphyria (EPP) is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excessive production and biliary excretion of protoporphyrin. The main clinical features—photosensitivity and hepatobiliary disease that may progress to liver failure—are caused by the toxicity of protoporphyrin. Orthotopic liver transplantation is an effective treatment of liver failure caused by EPP. In this report we have described an EPP Chinese man with end-stage liver disease. He was successfully transplanted. A 3-year follow-up study of protoporphyrin levels, liver tests, and liver biopsies showed no EPP recurrence after liver transplantation.

Comparison of intravascular ultrasonic imaging with versus without incomplete stent apposition at follow-up after drug-eluting stent implantation

Abstract: Background Incomplete stent apposition (ISA) at follow-up has been reported to be more common after drug-eluting stent (DES) implantation than after bare-metal stent (BMS) implantation. The aim of this study was to use intravascular ultrasound (IVUS) to evaluate the coronary characteristics after drug-eluting stent implantation in patients with ISA at follow-up. Methods From the IVUS database of our institute, a total of 89 patients with 125 native lesions who underwent DES implantation into de novo lesions with IVUS imaging at 6-month follow-up were identified, and 15 (16.9%) patients had documented ISA at follow-up by IVUS. The ISA group was compared with a matched control group of patients (n = 30) who had no evidence of ISA at follow-up. Results Of the 15 documented ISA at follow-up after DES implantation, two located at the edge (within 5 mm from stent margin) while 13 in the body of the stent. The maximum area and arc of ISA measured 5.3 ± 2.2 mm2 and 163 ± 67°, respectively. In patients with ISA, the maximum EEM area of stent segment with ISA was significantly larger than the adjacent stent segment without ISA (24.1 ± 3.3 vs. 20.1 ± 3.1 mm2, P = 0.002), while stent area, plaque plus media (P&M) area and intrastent lumen area were comparable (P > 0.05). Compared to the matched control cohort without ISA at follow-up, the maximum EEM area was also significantly larger (24.1 ± 3.3 vs. 18.8 ± 4.2 mm2, P 0.05). Conclusion ISA at follow-up after DES implantation for de novo coronary lesions was associated with a larger EEM area.

Coexistent in-stent restenosis, late incomplete stent apposition and mural thrombus in a zotarolimus-eluting stent.

Abstract: Drug-eluting stents (DES) have been demonstrated to dramatically reduce the rate of in-stent restenosis (ISR). However, some studies found an increased rate of late incomplete stent apposition (ISA) and late stent thrombosis (ST) in DES compared to traditional bare-metal stents (BMS). Endeavor stent, a new cobalt-alloy DES coated with phosphorylcholine and zotarolimus, has been reported to have a very favorable safety profile with few documented late-acquired ISA and late ST. In the present report, we described an interesting case with coexistent ISR, late ISA and mural thrombus in an Endeavor zotarolimus-eluting stent 8 months after primary percutaneous coronary intervention.

Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension.

Abstract: Portopulmonary hypertension (PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension, with or without advanced hepatic disease. Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state. Similar signs of advanced liver disease can be observed in severe PPH, with ascites and lower extremity edema. Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation (LT). We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis. Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years, it was necessary to send him to the intensive care unit after operation. Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality.