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1.  Remodeling of Kv1.5 Channel in Right Atria from Han Chinese Patients with Atrial Fibrillation 
The incidence of atrial fibrillation (AF) in rheumatic heart diseases (RHD) is very high and increases with age. Occurrence and maintenance of AF are very complicated process accompanied by many different mechanisms. Ion-channel remodeling, including the voltage-gated potassium channel Kv1.5, plays an important role in the pathophysiology of AF. However, the changes of Kv1.5 channel expression in Han Chinese patients with RHD and AF remain poorly understood. The aim of the present study was to investigate whether the Kv1.5 channels of the right atria may be altered with RHD, age, and sex to contribute to AF.
Right atrial appendages were obtained from 20 patients with normal cardiac functions who had undergone surgery, and 26 patients with AF. Subjects were picked from 4 groups: adult and aged patients in normal sinus rhythm (SR) and AF. Patients were divided into non-RHD and RHD groups or men and women groups in normal SR and AF, respectively. The expression of Kv1.5 protein and messenger RNA (mRNA) were measured using Western blotting and polymerase chain reaction (PCR) method, respectively.
Compared with the SR group, the expression of Kv1.5 protein decreased significantly in the AF group. However, neither Kv1.5 protein nor KCNA5 mRNA had significant differences in adult and aged groups, non-RHD and RHD group, and men and women group of AF.
The expression of Kv1.5 channel protein changes with AF but not with age, RHD, and sex in AF.
PMCID: PMC4424910  PMID: 25918274
Aging; Atrial Fibrillation; Kv1.5 Potassium Channel; Rheumatic Heart Disease; Sex
2.  EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome 
BMC Medical Genetics  2015;16:23.
Waardenburg syndrome type I (WS1), an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1.
Case presentation
We reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature (83.5 cm (−5.8SD)). His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 (IGF-1) was 52.7 ng/ml, lower than the normal range (55 ~ 452 ng/ml) and the peak growth hormone level was 7.57 ng/ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone (rhGH) replacement therapy, showing a 9.2 cm/year growth rate and an improvement of 1 standard deviation (SD) of height after one year treatment. CMA test of patient’s DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 (hg19; chr2:221,234,146-225,697,363).
PAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.
PMCID: PMC4432946  PMID: 25928000
Chromosomal microarray; 2q35-q36.2; PAX3; Waardenburg syndrome; EPHA4; Short stature
3.  Clinical and molecular evaluations of siblings with “pure” 11q23.3-qter trisomy or reciprocal monosomy due to a familial translocation t (10;11) (q26;q23.3) 
11qter trisomy is rare, mostly occurs in combination with partial monosomy of a terminal segment of another chromosome due to unbalanced segregation of parental translocations. Pure 11qter trisomy is rarer, only five cases have so far been reported. Here we report a family with all four siblings affected with neurodevelopmental disorders and facial dysmorphism. Chromosomal microarray analysis (CMA) identified 11q23.3-qter (15.1 Mb) deletion in one and reciprocal duplication in the other three siblings. Both father and grandfather are balanced translocation (46, XY, t (10;11) (q26;q23)) carriers. The genetic material involved on chromosome 10 is very limited (270 kb). Thus, the pedigree presented rare cases with “pure” 11qter trisomy or reciprocal 11qter monosomy (Jacobsen syndrome), offering a unique opportunity to examine clinical presentations of multiple individuals with identical genomic imbalance.
The proband with 11qter monosomy presented with many features of Jacobsen syndrome. The three 11qter trisomy carriers presented with shared craniofacial features including brachycephaly and short philtrum. They are also significant for the following neurodevelopmental and neuropsychiatric defects: intellectual disability, expressive language deficiency, autistic features, auditory hallucination, self-talking and pain insensitivity. To our knowledge, this is the smallest “pure” trisomy 11qter so far reported and this is the first report to describe the neuropsychiatric features of patients with 11qter trisomy. Our observation also revealed dissimilar features in our patients compared with those of previously published trisomy 11qter cases. The pedigree also revealed phenotypic heterogeneity among siblings with identical genomic imbalance.
PMCID: PMC4314806  PMID: 25648949
Jacobsen syndrome; 11q23.3-qter trisomy; 11q23.3-qter monosomy; SNP array; Familial translocation
4.  Implant-Related Infection in the Tibia: Surgical Revision Strategy with Vancomycin Cement 
The Scientific World Journal  2014;2014:124864.
The development of a deep wound infection in the presence of internal hardware presents a clinical dilemma. The purpose of the present study was to evaluate the treatment outcomes of vancomycin cement with other advances of surgical techniques for implant-related infection (IRI) in the tibia. This study included 217 consecutive patients who had sustained IRI of the tibia. Of them, 152 patients had soft tissue defects and the internal hardware was exposed. Repeated debridement and negative pressure assisted closure were used. All the infected internal hardware was removed. External fixations and flaps were used. Custom-made vancomycin cement was inserted into the dead space of the wounds and left in site for a month. The follow-up was from 12 months to 108 months, averaging 37.5 months. For all the 217 patients, the general osteomyelitis healing rate and bone union rate were 86.6% and 97.2%, respectively. This study shows high rates of healing of IRI in the tibia if the new advances of surgery could be effectively combined into the treatment strategy with vancomycin cement as an important treatment.
PMCID: PMC4238266  PMID: 25431774
5.  Crystal structure of (Z)-2-hy­droxy-4-methyl-N′-(4-oxo-1,3-thia­zolidin-2-yl­idene)benzohydrazide trihydrate 
In the title compound, C11H11N3O3S·3H2O, the non-H atoms of the main mol­ecule are approximately planar, with an r.m.s. deviation of 0.030 Å. There is a bifurcated intra­molecular N—H⋯(O,S) hydrogen bond present forming S(6) and S(5) ring motifs. In the crystal, O—H⋯O and N—H⋯O hydrogen bonds link the molecules into a three-dimensional network.
PMCID: PMC4257310  PMID: 25484827
crystal structure; benzohydrazide; 1,3-thia­zol­idene; hydrogen bonding; biological activity
6.  A Rare Fungal Species, Quambalaria cyanescens, Isolated from a Patient after Augmentation Mammoplasty – Environmental Contaminant or Pathogen? 
PLoS ONE  2014;9(10):e106949.
Some emerging but less common human fungal pathogens are known environmental species and could be of low virulence. Meanwhile, some species have natural antifungal drug resistance, which may pose significant clinical diagnosis and treatment challenges. Implant breast augmentation is one of the most frequently performed surgical procedures in China, and fungal infection of breast implants is considered rare. Here we report the isolation of a rare human fungal species, Quambalaria cyanescens, from a female patient in China. The patient had undergone bilateral augmentation mammoplasty 11 years ago and was admitted to Peking Union Medical College Hospital on 15 September 2011 with primary diagnosis of breast infection. She underwent surgery to remove the implant and fully recovered thereafter. During surgery, implants and surrounding tissues were removed and sent for histopathology and microbiology examination. Our careful review showed that there was no solid histopathologic evidence of infection apart from inflammation. However, a fungal strain, which was initially misidentified as “Candida tropicalis” because of the similar appearance on CHROMagar Candida, was recovered. The organism was later on re-identified as Q. cyanescens, based on sequencing of the rDNA internal transcribed spacer region rather than the D1/D2 domain of 26S rDNA. It exhibited high MICs to 5-flucytosine and all echinocandins, but appeared more susceptible to amphotericin B and azoles tested. The possible pathogenic role of Q. cyanescens in breast implants is discussed in this case, and the increased potential for misidentification of the isolate is a cause for concern as it may lead to inappropriate antifungal treatment.
PMCID: PMC4203675  PMID: 25330078
7.  Crystal structure of (Z)-2-hy­droxy-N′-(4-oxo-1,3-thia­zolidin-2-yl­idene)benzohydrazide 
In the title compound, C10H9N3O3S, the five-membered ring adopts a slightly twisted conformation about the Cm—S (m = methyl­ene) bond. The dihedral angle between this ring and the benzene ring is 7.99 (9)°. A bifurcated intra­molecular N—H⋯(O,S) hydrogen bond helps to establish the near planar conformation of the mol­ecule. In the crystal, mol­ecules are linked by N—H⋯O and O—H⋯O hydrogen bonds to generate (001) sheets.
PMCID: PMC4257235  PMID: 25484807
crystal structure; benzohydrazide; 4-thia­zolidinone derivatives; biological activity; hydrogen bonding
8.  Sortase A Induces Th17-Mediated and Antibody-Independent Immunity to Heterologous Serotypes of Group A Streptococci 
PLoS ONE  2014;9(9):e107638.
Group A streptococci (GAS) are associated with a variety of mucosal and invasive human infections. Recurrent infections by highly heterologous serotypes indicate that cross-serotype immunity is critical for prevention of GAS infections; however, mechanisms underlying serotype-independent protection are poorly understood. Here we report that intranasal vaccination of mice with Sortase A (SrtA), a conserved cell wall bound protein, reduced colonization of nasal-associated lymphoid tissue (NALT) by heterologous serotypes of GAS. Vaccination significantly increased CD4+ IL-17A+ cells in NALT and depletion of IL-17A by neutralizing antibody prevented GAS clearance from NALT which was dependent on immunization with SrtA. Vaccination also induced high levels of SrtA-specific antibodies; however, immunized, B cell-deficient mice cleared streptococcal challenges as efficiently as wild type mice, indicating that the cross-serotype protection is Th17-biased and antibody-independent. Furthermore, efficient GAS clearance from NALT was associated with a rapid neutrophil influx into NALT of immunized mice. These results suggest that serotype independent immune protection against GAS mucosal infection can be achieved by intranasal vaccination with SrtA and enhanced neutrophil function is critical for anti-GAS defense and might be a target for prevention of GAS infections.
PMCID: PMC4169422  PMID: 25232948
9.  A universal electromagnetic energy conversion adapter based on a metamaterial absorber 
Scientific Reports  2014;4:6301.
On the heels of metamaterial absorbers (MAs) which produce near perfect electromagnetic (EM) absorption and emission, we propose a universal electromagnetic energy conversion adapter (UEECA) based on MA. By choosing the appropriate energy converting sensors, the UEECA is able to achieve near 100% signal transfer ratio between EM energy and various forms of energy such as thermal, DC electric, or higher harmonic EM energy. The inherited subwavelength dimension and the EM field intensity enhancement can further empower UEECA in many critical applications such as energy harvesting, photoconductive antennas, and nonlinear optics. The principle of UEECA is understood with a transmission line model, which further provides a design strategy that can incorporate a variety of energy conversion devices. The concept is experimentally validated at a microwave frequency with a signal transfer ratio of 96% by choosing an RF diode as the energy converting sensor.
PMCID: PMC4158331  PMID: 25200005
10.  Diagnostic Accuracy of Intracellular Mycobacterium tuberculosis Detection for Tuberculous Meningitis 
Rationale: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity.
Objectives: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis.
Methods: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6–expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients’ final diagnosis.
Measurements and Main Results: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6–6.7%), compared with 82.9% (95% confidence interval, 77.4–87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8–80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4–93.8%) and 90.0% (95% confidence interval, 75.4–96.7%), respectively.
Conclusions: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.
PMCID: PMC3977721  PMID: 24450377
tuberculosis; central nervous system; cerebrospinal fluid; diagnosis
11.  Yeast Identification Algorithm Based on Use of the Vitek MS System Selectively Supplemented with Ribosomal DNA Sequencing: Proposal of a Reference Assay for Invasive Fungal Surveillance Programs in China 
Journal of Clinical Microbiology  2014;52(2):572-577.
Sequence analysis of the internal transcribed spacer (ITS) region was employed as the gold standard method for yeast identification in the China Hospital Invasive Fungal Surveillance Net (CHIF-NET). It has subsequently been found that matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is potentially a more practical approach for this purpose. In the present study, the performance of the Vitek MS v2.0 system for the identification of yeast isolates collected from patients with invasive fungal infections in the 2011 CHIF-NET was evaluated. A total of 1,243 isolates representing 31 yeast species were analyzed, and the identification results by the Vitek MS v2.0 system were compared to those obtained by ITS sequence analysis. By the Vitek MS v2.0 system, 96.7% (n = 1,202) of the isolates were correctly assigned to the species level and 0.2% (n = 2) of the isolates were identified to the genus level, while 2.4% (n = 30) and 0.7% (n = 9) of the isolates were unidentified and misidentified, respectively. After retesting of the unidentified and misidentified strains, 97.3% (n = 1,209) of the isolates were correctly identified to the species level. Based on these results, a testing algorithm that combines the use of the Vitek MS system with selected supplementary ribosomal DNA (rDNA) sequencing was developed and validated for yeast identification purposes. By employing this algorithm, 99.7% (1,240/1,243) of the study isolates were accurately identified with the exception of two isolates of Candida fermentati and one isolate of Cryptococcus gattii. In conclusion, the proposed identification algorithm could be practically implemented in strategic programs of fungal infection surveillance.
PMCID: PMC3911352  PMID: 24478490
12.  Sero-Survey of Polio Antibodies during Wild Poliovirus Outbreak in Southern Xinjiang Uygur Autonomous Region, China 
PLoS ONE  2014;9(7):e80069.
After being polio free for more than 10 years, an outbreak following importation of wild poliovirus (WPV) was confirmed in Xinjiang Uygur Autonomous Region, China, in 2011.
A cross-sectional study was conducted prior to supplementary immunization activities (SIAs), immediately after the confirmation of the WPV outbreak. In selected prefectures, participants aged ≤60 years old who visited hospitals at county-level or above to have their blood drawn for reasons not related to the study, were invited to participate in our study. Antibody titers ≥8 were considered positive.
Among the 2,611 participants enrolled, 2,253 (86.3%), 2,283 (87.4%), and 1,989 (76.2%) were seropositive to P1, P2 and P3 respectively, and 1744 (66.8%) participants were seropositive to all the three serotypes. Lower antibody seropositivities and geometric mean titers were observed in children <1 year of age and in adults aged 15–39 years.
Serosurveys to estimate population immunity in districts at high risk of polio importation might be useful to gauge underlying population immunity gaps to polio and possibly to guide preparedness and response planning. Consideration should be given to older children and adults during polio risk assessment planning and outbreak response.
PMCID: PMC4081020  PMID: 24991811
13.  Dominance of CTX-M-Type Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli Isolated from Patients with Community-Onset and Hospital-Onset Infection in China 
PLoS ONE  2014;9(7):e100707.
To investigate CTX-M genotypes among extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) isolated from patients with community-onset and hospital-onset infections in China, their clonality and the distribution of CTX-M variants in different specimens of community-onset and hospital-onset infections.
ESBL-EC isolates were collected from general hospitals from 2011 to 2012 in China. Broth microdilution method antimicrobial susceptibility testing of 16 antibiotics was performed. Clinical data from community-onset and hospital-onset infections due to ESBL-EC were analyzed. ESBL-encoding genes were amplified by PCR and sequenced, and multilocus sequence typing (MLST) was performed for a random selection of predominant CTX-M type strains identified.
A total of 1,168 ESBL-EC isolates were obtained from various clinical specimens, 41.7% of which were responsible for causing community-onset infections. The presence of urinary calculi was higher in community-onset infections, whereas malignancy, cardiovascular and cerebrovascular diseases, dementia, chronic renal disease, diabetes mellitus and surgical treatment were found to have higher proportions in hospital-onset infections. There was no significant difference in trauma between community-onset and hospital-onset infections. 96.2% of the isolates were detected to harbor blaCTX-M genes. blaCTX-M-1 group and blaCTX-M-9 group were detected at 40.7% and 48.7% respectively, and both positive group accounted for 10.6%. blaCTX-M-55 (24.8%) and blaCTX-M-15 (18.2%) were the major genotypes in blaCTX-M-1 group while blaCTX-M-14 (46.8%) was predominant in blaCTX-M-9 group. A comparison of blaCTX-M distribution in different specimens between ESBL-EC causing community-onset and hospital-onset infection showed no significant difference. A total of 229 isolates were tested for MLST. ST131 (14%) was the predominant type. ST648, ST405 and ST1193 were also detected.
Community-onset ESBL-EC has emerged as a common pathogen in China. CTX-M-14 is the most commonly encountered, CTX-M-55 and CTX-M-15 have spread rapidly. ST131 is the predominant clonal group, and the great diversity of CTX-M-producing isolates of E. coli has emerged in China.
PMCID: PMC4077569  PMID: 24983621
14.  Beclin 1 Deficiency Correlated with Lymph Node Metastasis, Predicts a Distinct Outcome in Intrahepatic and Extrahepatic Cholangiocarcinoma 
PLoS ONE  2013;8(11):e80317.
Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC.
PMCID: PMC3841169  PMID: 24303007
15.  A practical guide to treatment of infantile hemangiomas of the head and neck 
Infantile hemangiomas are the most common benign vascular tumors in infancy and childhood. As hemangioma could regress spontaneously, it generally does not require treatment unless proliferation interferes with normal function or gives rise to risk of serious disfigurement and complications unlikely to resolve without treatment. Various methods for treating infant hemangiomas have been documented, including wait and see policy, laser therapy, drug therapy, sclerotherapy, radiotherapy, surgery and so on, but none of these therapies can be used for all hemangiomas. To obtain the best treatment outcomes, the treatment protocol should be individualized and comprehensive as well as sequential. Based on published literature and clinical experiences, we established a treatment guideline in order to provide criteria for the management of head and neck hemangiomas. This protocol will be renewed and updated to include and reflect any cutting-edge medical knowledge, and provide the newest treatment modalities which will benefit our patients.
PMCID: PMC3832322  PMID: 24260591
Hemangiomas; treatment; head and neck; sclerotherapy; drug therapy
16.  Distinctive disruption patterns of white matter tracts in Alzheimer’s disease with full diffusion tensor characterization 
Neurobiology of Aging  2011;33(9):2029-2045.
To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with four metrics derived from DTI, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association and projection tracts, include white matter tracts of similar functions. DTI data were acquired from 61 subjects (26 AD, 11 subjects with amnestic mild cognitive impairment or aMCI, 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association and projection tract groups between control and AD subjects. Specifically, FA, MD and RD of limbic tracts, FA, MD, AxD and RD of commissural tracts, MD, AxD and RD of association tracts and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between MCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage.
PMCID: PMC3227739  PMID: 21872362
Alzheimer’s disease; atlas; DTI; white matter tract; tract group; biomarker
17.  Decreases in Electrocardiographic R-Wave Amplitude and QT Interval Predict Myocardial Ischemic Infarction in Rhesus Monkeys with Left Anterior Descending Artery Ligation 
PLoS ONE  2013;8(8):e71876.
Clinical studies have demonstrated the predictive values of changes in electrocardiographic (ECG) parameters for the preexisting myocardial ischemic infarction. However, a simple and early predictor for the subsequent development of myocardial infarction during the ischemic phase is of significant value for the identification of ischemic patients at high risk. The present study was undertaken by using non-human primate model of myocardial ischemic infarction to fulfill this gap. Twenty male Rhesus monkeys at age of 2–3 years old were subjected to left anterior descending artery ligation. This ligation was performed at varying position along the artery so that it produced varying sizes of myocardial infarction at the late stage. The ECG recording was undertaken before the surgical procedure, at 2 h after the ligation, and 8 weeks after the surgery for each animal. The correlation of the changes in the ECG waves in the early or the late stage with the myocardial infarction size was analyzed. The R wave depression and the QT shortening in the early ischemic stage were found to have an inverse correlation with the myocardial infarction size. At the late stage, the R wave depression, the QT prolongation, the QRS score, and the ST segment elevation were all closely correlated with the developed infarction size. The poor R wave progression was identified at both the early ischemic and the late infarction stages. Therefore, the present study using non-human primate model of myocardial ischemic infarction identified the decreases in the R wave and the QT interval as early predictors of myocardial infarction. Validation of these parameters in clinical studies would greatly help identifying patients with myocardial ischemia at high risk for the subsequent development of myocardial infarction.
PMCID: PMC3742514  PMID: 23967258
18.  Guidelines for the treatment of head and neck venous malformations 
Venous malformation is one of the most common benign vascular lesions, with approximately 40% of cases appearing in the head and neck. They can affect a patient’s appearance and functionality and even cause life-threatening bleeding or respiratory tract obstruction. The current methods of treatment include surgery, laser therapy, sclerotherapy, or a combined. The treatment of small and superficial venous malformations is relatively simple and effective; however, the treatment of deep and extensive lesions involving multiple anatomical sites remains a challenge for the physicians. For complex cases, the outcomes achieved with one single treatment approach are poor; therefore, individualized treatment modalities must be formulated based on the patient’s condition and the techniques available. Comprehensive multidisciplinary treatments have been adapted to achieve the most effective results. In this paper, based on the national and international literature, we formulated the treatment guidelines for head and neck venous malformations to standardize clinical practice. The guideline will be renewed and updated in a timely manner to reflect cutting-edge knowledge and to provide the best treatment modalities for patients.
PMCID: PMC3664006  PMID: 23724158
Head and neck; venous malformation; treatment guidelines
19.  Application of liposomes in drug development — focus on gastroenterological targets 
Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer.
PMCID: PMC3623572  PMID: 23630417
liposome; colorectal cancer; inflammatory bowel disease; drug delivery
20.  A Preliminary Investigation of Corpus Callosum and Anterior Commissure Aberrations in Aggressive Youth with Bipolar Disorders 
Although behavioral deficits in bipolar disorder (BPD) are well described, the specific brain white matter (WM) disruptions have not been completely characterized, and neural mechanisms underlying dysfunction in BPD are not well established, particularly for youth with BPD and aggression. This preliminary study utilized diffusion tensor imaging (DTI) to investigate commissural tracts (corpus callosum [CC] and anterior commissure [AC]) in youth with BPD, because disruption of interhemispheric communication may contribute to the emotional deficits that are characteristic of the illness.
DTI was used to investigate WM in 10 youth (7–17 years of age) with BPD and 10 typically developing age-matched controls. Tract-based spatial statistics voxel-wise analysis was used to compare fractional anisotropy (FA) of the two groups. We specifically focused on five subdivisions of the midsagittal CC as well as on the decussation of AC, which connects the temporal lobes. Exploratory correlations between FA values and life history of aggression scores were calculated for the BPD group.
Youth with BPD had significantly lower FA values in the callosal genu and AC. FA values in the AC were negatively correlated with a life history of aggression in the BPD group.
These results contribute to a growing literature implicating a role for the genu of the CC in BPD and are the first to report WM variations in the AC of children with BPD. Taken together with the correlational data for aggression and the role of the AC in emotional processing, our data provide preliminary evidence for a possible association between the structural integrity of the WM of the AC and aggression in pediatric BPD.
PMCID: PMC3362324  PMID: 22375854
22.  Delayed liver laceration following transjugular intrahepatic portosystemic shunt for portal hypertension 
The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. Delayed liver laceration is a rare complication of the TIPS procedure. We describe a patient with portal hypertension due to liver cirrhosis, who suddenly presented with abdominal hemorrhage and liver laceration 8 d after TIPS. Few reports have described complications after TIPS placement. To the best of our knowledge, this is the first report describing delayed liver laceration. This potential and serious complication appears to be specific and fatal for TIPS in portal hypertension. We advocate careful attention to the technique to avoid this complication, and timely treatment is extremely important.
PMCID: PMC3544050  PMID: 23326153
Transjugular intrahepatic portosystemic shunt; Portal hypertension; Liver cirrhosis; Postoperative complications; Hemorrhage
23.  Significance of decoy receptor 3 (Dcr3) and external-signal regulated kinase 1/2 (Erk1/2) in gastric cancer 
BMC Immunology  2012;13:28.
Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is associated with anti-tumor immunity suppression. It is highly expressed in many tumors, and its expression can be regulated by the MAPK/MEK/ERK signaling pathway. The MAPK/MEK/ERK pathway has been reported to be a regulator in tumor occurrence, development and clonal expansion. External-signal regulated kinase (ERK) is a vital member of this pathway.
The expression of DcR3 and ERK1/2 in tumor tissues of gastric cancer patients was significantly higher than the non-cancerous group (P < 0.05). There was no statistical difference among tumor tissues from patients with different ages or gender, and even of different differentiation (P > 0.05). However, in patients with stage I gastric cancer, the DcR3 and ERK1/2 levels were significantly lower than patients with more advanced stages.
DcR3 and ERK1/2 play a vital role in the development of gastric cancer, and they may be new markers for indicating the efficiency of gastric cancer treatment in the future.
PMCID: PMC3459731  PMID: 22672288
24.  Autologous Transplantation of Lentivector/Acid Ceramidase–Transduced Hematopoietic Cells in Nonhuman Primates 
Human Gene Therapy  2011;22(6):679-687.
Farber disease is a rare lysosomal storage disorder (LSD) that manifests due to acid ceramidase (AC) deficiencies and ceramide accumulation. We present a preclinical gene therapy study for Farber disease employing a lentiviral vector (LV-huAC/huCD25) in three enzymatically normal nonhuman primates. Autologous, mobilized peripheral blood (PB) cells were transduced and infused into fully myelo-ablated recipients with tracking for at least 1 year. Outcomes were assessed by measuring the AC specific activity, ceramide levels, vector persistence/integration, and safety parameters. We observed no hematological, biochemical, radiological, or pathological abnormalities. Hematological recovery occurred by approximately 3 weeks. Vector persistence was observed in PB and bone marrow (BM) cells by qualitative and quantitative PCR. We did not observe any clonal proliferation of PB and BM cells. Importantly, AC-specific activity was detected above normal levels in PB and BM cells analyzed post-transplantation and in spleens and livers at the endpoint of the study. Decreases of ceramide in PB cells as well as in spleen and liver tissues were seen. We expect that this study will provide a roadmap for implementation of clinical gene therapy protocols targeting hematopoietic cells for Farber disease and other LSDs.
Farber disease is a rare autosomal recessive condition resulting from reduced or absent acid ceramidase (AC; EC activity. In this study, Neschadim et al. present results from a preclinical study wherein autologous lentivector/AC–transduced hematopoietic cells were infused into enzymatically normal nonhuman primates. Animals were tracked for 1 year, and no hematological, biochemical, radiological, or pathological abnormalities were observed. Importantly, AC-specific activity was detected above normal levels in peripheral blood and bone marrow cells analyzed post transplantation and in spleens and livers at the endpoint of the study.
PMCID: PMC3155125  PMID: 21280983
25.  Benzene-1,3,5-tricarbonyl trichloride 
In the title molecule, C9H3Cl3O3, there are three short interactions involving the benzene H atoms and the chloro­formyl Cl atoms. In the crystal, mol­ecules stack along the a axis with no significant non-bonded inter­actions.
PMCID: PMC3344186  PMID: 22606189

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