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Biomedical subjects

Yan Shen

Publications and source records attributed to Yan Shen.

At least 37 records · Page 2Linked to original sources

[Effects of ciclosporin and tacrolimus on replication of hepatitis B virus in vitro: a comparative study].

OBJECTIVE: To investigate the effects of ciclosporin (CsA) and tacrolimus (FK506) on replication of hepatitis B virus (HBV) in vitro. METHODS: HBV genome permanently transfected human liver cancer cells of the line HepG2.2.15 were cultured. CsA and FK506 at different concentrations were added into the culture fluid so as to identify the nontoxic concentrations by MTT method. Then the HepG2.2.15 cells were treated by CsA and FK506 at different nontoxic concentrations respectively for 4 days. ELISA was used to detect the HB surface antigen (HBsAg) and HB e antigen (HBeAg) in the supernatant. The relative replication level of HBV DNA was detected by slot blot analysis. RESULTS: MTT method confirmed that the nontoxic concentrations of CsA and FK506 were 0-40.0 microg/ml and 0-400 ng/ml respectively. After the treatment of CsA at the concentration of 1.3, 2.5, and 5.0 microg/ml, in comparison to the control group, the suppression rates of HBsAg expression in the HepG2.2.15 cells were 16.5% +/- 9.4%, 21.5% +/- 8.9%, and 33.1% +/- 5.3% respectively (all P < 0.05); the suppression rates of HBeAg expression in the HepG2.2.15 cells were 7.8% +/- 2.2%, 11.0% +/- 2.3%, and 20.8% +/- 1.5% respectively (all P < 0.05); and the HBV DNA replication levels were 56 +/- 16, 42 +/- 11, and 40 +/- 10 respectively (P > 0.05, P < 0.05, and P > 0.05). However, FK506 at different nontoxic concentrations showed no significant inhibitory effect on the levels of HBsAg, HBeAg, and HBV DNA. CONCLUSION: CsA dose-dependently inhibits the HBV replication in vitro, and FK506 does not exercise similar effects.

Cell Line, Tumor↗

Prevention of hepatitis B recurrence after liver transplantation using lamivudine or lamivudine combined with hepatitis B Immunoglobulin prophylaxis.

The aim of our study was to determine the outcomes of liver transplant recipients receiving either lamivudine (LAM) monotherapy or LAM combined with low-dose intramuscular (IM) hepatitis B Immunoglobulin (HBIG) therapy. We performed a retrospective review of the medical records of patients that had had liver transplantation in a single center for HBV-related liver diseases from December 1999 to June 2004. A total of 165 patients received LAM monotherapy (51 patients) or combined prophylaxis (114 patients) post-liver transplantation (LT) with a mean follow-up of 20.13 months. Hepatitis B relapsed in 21 patients of the hepatitis B surface antigen (HBsAg) carriers who received LAM monotherapy, with a 1- and 2-yr actuarial risk of 27.4% and 39.7%. Recurrence occurred in 16 patients of 114 patients receiving the combined prophylaxis, with a 1- and 2-yr recurrence rate of 13.5% and 15.2% (P = 0.024). A total of 25 cases (67.6%) with YMDD mutants were detected in all the 37 patients, 14 cases (66.7%) in the monotherapy group and 11 cases (68.8%) in the combination group. In conclusion, LAM and low-dose intramuscular HBIG treatment demonstrates a better result than LAM monotherapy, as prophylaxis against post-LT reinfection of the graft, but the safety and efficacy as a substitution for high-dose intravenous HBIG with LAM needs to be investigated further.

Adult↗

CACNA1I is not associated with childhood absence epilepsy in the Chinese Han population.

This study investigated whether the T-type calcium channel gene CACNA1I causes susceptibility in the Chinese Han population to childhood absence epilepsy, a form of idiopathic generalized seizure disorder. For this investigation, we searched for mutations in the 35 exons and exon-intron boundaries of the CACNA1I gene in 50 Han Chinese patients with childhood absence epilepsy. Seventeen single nucleotide polymorphisms were identified in the 35 exons. Using six single nucleotide polymorphisms as markers, the allele and genotype distributions of all of the identified single nucleotide polymorphisms were examined; there was no significant difference between the childhood absence epilepsy cases and the control groups. Thus, we do not consider the CACNA1I gene to be an important susceptibility gene for childhood absence epilepsy in the Chinese Han population.

Adolescent↗

Expression of BIRC7 protein and mRNA in non-Hodgkin's lymphoma.

Studies have shown that BIRC7, a new member of inhibitor of the apoptosis protein family, is expressed in fetal tissues and most solid tumors in humans. However, there are no reported data concerning BIRC7 expression in lymphomas. We investigated the expression of BIRC7, survivin, Bcl-2, Bax, p53 and p170 proteins in 167 cases of non-Hodgkin's lymphoma (NHL) and 10 cases of non-specific lymphadenitis by tissue microarray-based immunohistochemistry. BIRC7 mRNA in three cell lines and 16 cases of NHL were detected by reverse transcriptase-polymerase chain reaction. BIRC7 protein was exhibited in the cytoplasm of cells in 25 (31%) of 80 cases of B-NHLs, 32 (37%) of 87 cases of T-NHLs, and none in non-specific lymphadenitis. The positive rate of BIRC7 was lower than that of survivin in almost all types of NHL with no significant differences, and similar to that of Bcl-2, Bax or p53. There was no correlation of protein expression between BIRC7 and any other detected markers, except p170 in T-NHL (P < 0.001). BIRC7 expression did not correlate with clinic pathologic factors such as sex, age, stage and grade, but overexpression of BIRC7 was positively correlated with aggression of NHL cells (P < 0.05). BIRC7 mRNA expressed in six (38%) of 16 cases of NHLs. BIRC7 mRNA expression was approximately consistent with BIRC7 protein in NHL. Our results indicate that the BIRC7 gene might play a role in the development and aggression of NHL and that the inhibition of BIRC7 expression may be important in NHL treatment.

Adaptor Proteins, Signal Transducing↗

A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family.

OBJECTIVES/HYPOTHESIS: It is known that approximately 5% of congenital profound hearing impaired cases are inherited in X-linked inheritance. This study aimed at identifying its underlying molecular determinant(s) using a large, five-generation Chinese family with multiple familial cases. STUDY DESIGN: Model-based linkage analysis and positional cloning. METHODS: Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine disease locus. Mutation screening was performed within the family and unrelated population-based controls to establish molecular evidence as to what caused the specific X-linked inheritance pattern in the family. RESULTS: Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.I-Xq23 (maximum X-linkage logarithm of odds score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T>C) in the well-known deaf gene. POU3F4. Direct sequencing on 240 unrelated controls did not detect any mutation. CONCLUSIONS: Multiple analysis approaches demonstrated that these disorders in the family were caused by a founder mutation in the POU3F4 gene. Our findings provided confirmatory molecular evidence to support that development of congenital profound sensorineural hearing loss in the Chinese population results from a novel mutation in the same gene.

Adolescent↗

A novel recently evolved gene C19orf24 encodes a non-classical secreted protein.

Secreted proteins play important roles in many crucial biological processes, and can be new agents or targets for drug therapies. Here, we report on the isolation and characterization of a novel human non-classical secreted protein which is encoded by the hypothetical gene C19orf24 (chromosome 19 open reading frame 24). It has no signal peptide, but can still secrete extracellularly despite the presence of the inhibitor brefeldin A (BFA), proving its non-classical secreted protein status. Via subcellular localization using C19orf24 in vivo and transfected pEYFP-Golgi plasmid in Hela cells, C19orf24 was shown not to co-localize in the Golgi apparatus, which suggested that it secretes via a new and unknown pathway. Deglycosylation analysis with PNGase F verified that it has no N-glycosylation modification sites. Via the reverse transcription-PCR method, it was found to be expressed only in the human liver, and preferentially in normal tissue. In addition, C19orf24 was shown to be a recently evolved gene, found only in Homo sapiens and Pan troglodytes. By calculating its synonymous and non-synonymous substitution rate (d (S)/d (N)), we found that it experienced a purifying selection, which suggests that C19orf24 may have a special, irreplaceable biological function in the human organism.

Amino Acid Sequence↗

[An association study between paranoid schizophrenia and four genes involved in dopamine metabolism].

Schizophrenia is a complex disease caused by interactions among multiple genes. Reports of one of its susceptibility genes, ethyltracatechol-O-mnsferase (COMT) have been conflicting. In the present study on paranoid schizophrenia, we have performed a multilocus association study to analyze the interactions among 4 genes that are involved in dopamine metabolism. Result supports the hypothesis that COMT-136-BclI regulates Val108/158Met. When the genotype of the former is CC, Met (A) is the genotype of susceptibility allele Val108/158Met; and when the genotype of the former is GG, Val (G) is the genotype of susceptibility allele Val108/158Met. This new hypothesis may explain the conflicting results about Val108/158Met (COMT) obtained by single-locus analyses. It also illustrates that multilocus analysis is necessary for the research of complex diseases.

Adult↗

[Mutation analysis of SRD5A2 gene in patients with hypospadias].

OBJECTIVE: To explore possible molecular mechanism of hypospadias and relationship of the mutation of SRD5A2 gene to hypospadias. METHODS: 96 blood samples from the patients with hypospadias were obtained and DNA was extracted from blood leukocytes. Polymerase chain reaction and direct sequencing were performed to analyze the coding regions of SRD5A2 gene. RESULTS: 8 mutations were detected from 14 cases, including 5 missense mutations, 1 synonymous mutation, 1 nonsense mutation and 1 frameshift mutation. The mutations are in 1st, 4th and 5th exon. Gln6stop, His232His, Phe234Leu and frameshift mutations are novel. CONCLUSIONS: Exon 4 is a hot spot region of mutation within SRD5A2 gene, and about 10 percent of hypospadiac patients complicated with SRD5A2 dysfunction or deficiency.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Subcutaneous implantation of tissue-engineered heart valve leaflets in nude mice].

OBJECTIVE: To investigate the viability of tissue-engineered heart valve leaflets prepared with cell-polymer constructs in nude mice. METHODS: Sheep endothelial cells and smooth muscle cells/fibroblasts were seeded on patches of PHA and implanted subcutaneously in athymic mice (BALB/C). The cell-polymer constructs were harvested 12, 14, 21 and 28 days after implantation. RESULTS: Fourteen days after implantation, the cell-polymer constructs exhibited similar color with the autologous tissues, and HE staining showed more numerous cells in the implant. At 28 days following implantation, muscular fibers were formed in the cell-polymer constructs. V-G staining showed positive collagen staining in the implant at 12 days after implantation, while the control implants retrieved 28 days after implantation did not show extensive tissue formation or muscular fiber formation. CONCLUSION: The cell-polymer constructs can survive in vivo and has the potential to grow into autologous valve leaflets in the nude mice.

Animals↗

[The effect of CACNA1H gene G773D mutation on calcium channel function].

OBJECTIVE: To study the effect of CACNA1H gene mutation G773D on calcium channel function. METHODS: By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp technique, we studied the alterations of channel behavior in transfected HEK-293 cells. RESULTS: There were no difference in kinetics of activation and inactivation of calcium channel between wild type and mutant. However comparing with the wild-type Cav3.2 channel, G773D mutant could increase the calcium current density significantly. CONCLUSION: CACNA1H gene G773D mutation is able to increase calcium current and neuronal excitability.

Base Sequence↗

Diagnosis and treatment of solid-pseudopapillary tumor of the pancreas.

BACKGROUND: Solid-pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor. Despite the increasing recognition of the tumor in recent years, its pathogenesis and apparent therapeutic algorithm remain unclear. This study was designed to define the clinical, imaging, and pathologic features and to improve the diagnosis and treatment of this rare disease. METHOD: The clinical, imaging, and pathologic findings of 9 SPT patients managed in our hospital between 2001 and 2005 were retrospectively analyzed, and related literatures were reviewed. RESULTS: In the 9 patients aged from 14 to 68 years, 8 were female and 1 male. The mean age of these patients at diagnosis was 30 years. Initially, 8 patients complained of vague abdominal pain and one patient had pancreatic mass detected incidentally by abdominal CT. The levels of blood and urine amylase and tumor markers were all within the normal range. B-US, CT and MRI demonstrated that tumors were well encapsulated and contained some degree of internal hemorrhage or cystic degeneration. The mean transverse diameter of these tumors was 5.4 cm (range, 2-10.5 cm). The tumors were located at the head (2 patients), body (2), body and tail junction (4), and tail (1) of the pancreas. Surgical procedures included pancreaticoduodenectomy, distal pancreatectomy, distal pancreatectomy with splenectomy, and enucleation. Histological examination showed solidified cystic areas and papillary protrusions. Two malignant tumors demonstrated retroperitoneal metastases and vascular invasion. Follow-up for 2.5 years on average showed that one patient died of tumor recurrence at 10 months and the rest were alive. CONCLUSIONS: SPT exhibits unique clinical and pathologic features and is readily diagnosed by its characteristic imaging and histological appearance. Surgical resection of the primary tumor and metastases is the treatment of choice.

Adolescent↗

Common SNPs of APM1 gene are not associated with hypertension or obesity in Chinese population.

OBJECTIVE: To investigate whether the common variants 45T/G and 276G/T in APM1 gene were associated with hypertension combined with obesity (HO) and related clinical features in Chinese Han population. METHODS: A case-control study design was applied. Common polymorphisms of 45T/G and 276G/T were genotyped by PCR product sequencing in 484 cases with HO and 502 controls with normal blood presure and BMI < 25. RESULTS: The genotype and allele frequencies of 45T/G, 276G/T, and haplotype defined by the two variants in cases did not differ from those in controls. The means of blood pressure, BMI and waist-hip ratio did not differ among genotypes of the two polymorphisms and haplotypes. Among lipid profiles, only serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in T allele carriers than that in non-T carriers after adjusting possible confounding factors (1.21 vs 1.32 mmol/L, P=0.0001). CONCLUSION: Polymorphisms of 45T/G and 276G/T in APM1 gene are not associated with hypertension or obesity, or their clinical features in Chinese Han population. Common polymorphism of 45T/G might be associated with serum HDL-C levels in Chinese.

Adiponectin↗

A common profile for polymer-based controlled releases and its logical interpretation to general release process.

PURPOSE: The release of drug from a polymeric matrix is complicated. It often involves drug diffusion, interface movement and various interactions. It also shows a dependence on the length of polymer rod. With Lc as the 'critical length', three different phases can be distinguished from the kinetic process. Prior to reaching Lc, the interface movement plays a key role on determining the release. Otherwise, the drug diffusion can dominate the release process. Near Lc, however, both factors are involved. The rate of interface movement is closely associated with the time and position in the polymer rod. Taking these characters into account, a common model is presented in this article to be tentatively used to interpret the release process. These results provide preliminarily an insight into the understanding of controlled release process.

Chemistry, Pharmaceutical↗

[Clinical evaluation of emergency liver transplantation for patients with benign end-stage liver diseases].

OBJECTIVE: To evaluate the efficacy of emergency liver transplantation in treating patients with benign end-stage liver diseases and explore the possible prognostic factors. METHOD: The clinic data of 46 cases of recipients who underwent ELT were retrospectively analyzed. clinicopathological variables (including age, gender, etiology, serum creatinine, PT, INR, albumin, total bilirubin) were compared between the survival group (n = 32) and the dead group (n = 14). And the prognostic values of CTP and MELD score were analyzed. RESULTS: Higher serum creatinine level, MELD score and CTP score were found in the dead group, as compared to those in survival group. The survival rates among CTP or MELD categories showed significant difference. Three-and six months and one year survival rates of total recipients were 73.9% , 71.7% and 69.6% respectively. CONCLUSION: Emergency liver transplantation is an effective treatment to salvage patients in end-stage. Serum creatinine is the important prognostic factor to the posttransplant survival. MELD score system is more sensitive than CTP classification in predicting the prognosis.

Adult↗

Overexpression of the novel human gene, nuclear apoptosis-inducing factor 1, induces apoptosis.

Apoptosis is a genetically determined cell suicidal program that plays critical roles in many physiological and pathological processes. In this study, we report the cloning and characterization of a novel human gene, nuclear apoptosis-inducing factor 1 (NAIF1), overexpression of which induces apoptosis in cells. Human NAIF1 is located on chromosome 9q34.11 and encodes 327 amino acids with a homeodomain-like region and two nuclear localization signals at its N-terminal region. NAIF1 is conserved across diverse species, including human, mouse, crab-eating macaque, dog, chicken and frog, and shares no obvious homology to any known genes or proteins. Northern blot analysis revealed wide expression of NAIF1 mRNA throughout human tissues. NAIF1 was predominantly localized in the nucleus. Overexpression of NAIF1 inhibited cell growth and induced apoptosis. Furthermore, NAIF1 transfection caused both decreases in mitochondrial membrane potential and caspase-3 activation. In summary, NAIF1 is a nuclear protein that induces apoptosis when overexpressed.

Active Transport, Cell Nucleus↗

Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics.

There is accumulating evidence of altered antioxidant enzyme activities and increased levels of lipid peroxidation in schizophrenia. Free radical-mediated abnormalities may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. However, few studies have evaluated both antioxidant enzymes and lipid peroxidation in the same schizophrenic patient groups treated with typical or atypical antipsychotics. Plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 92 medicated schizophrenia including paranoid (n=34), disorganized (n=18) and residual subtypes (n=40), as well as in control subjects (n=50). The results showed that activities of SOD and GSH-Px were decreased but levels of MDA were elevated in patients with a chronic form of schizophrenia as compared with normal controls. SOD and GSH-Px activities were found to be significantly lower in paranoid and residual subtypes compared to both disorganized subtype and the control group. MDA levels were significantly higher in all subtypes compared to the control group. There were no significant differences in any parameters measured among all three subgroups treated with clozapine (n=44), risperidone (n=20) and typical antipsychotics (n=28). Additionally, a significantly higher MDA levels, but a significantly lower CAT activity was noted in female than male patients. These results suggest that oxidative stress may be implicated in the pathophysiology of all subtypes of schizophrenia, which may contribute to the increased membrane lipid peroxidation. Long-term treatments with typical and atypical antipsychotics may produce the similar effects on the antioxidant enzymes and lipid peroxidation.

Adult↗

Lack of GABABR1 gene variation (G1465A) in a Chinese population with temporal lobe epilepsy.

GABA(B) receptor1 (GABA(B)R1) gene is one of the susceptibility genes for temporal lobe epilepsy (TLE). Recently, it is reported that the GABA(B)R1 polymorphism (G1465A) conferred a highly increased susceptibility to TLE. We performed a case-control study to confirm the findings. The study included a total of 112 nonlesional TLE patients and 124 controls of Chinese ancestry. Our study did not show any polymorphism in this locus, and suggested this polymorphism may not be a strong susceptibility factor for TLE among Chinese population.

Adult↗

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery.

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.

DNA Transposable Elements↗