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Yan-Ping Zhang

Publications and source records attributed to Yan-Ping Zhang.

17 recordsLinked to original sources

Optical induction of synaptic plasticity using a light-sensitive channel.

We have combined millisecond activation of channelrhodopsin-2 (ChR2), a light-gated ion channel, with two-photon calcium imaging to investigate active synaptic contacts in rat hippocampal slice cultures. Calcium influx was larger during light-induced action potentials than during action potentials induced by somatic current injection, leading to highly reproducible synaptic transmission. Pairing of light stimulation with postsynaptic depolarization induced long-term potentiation, making this technique ideal for genetic and pharmacological dissection of synaptic plasticity.

Action Potentials↗

Differential compartmentalization and distinct functions of GABAB receptor variants.

GABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). Molecular diversity in the GABAB system arises from the GABAB1a and GABAB1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeats that is unique to GABAB1a. Using a combined genetic, physiological, and morphological approach, we now demonstrate that GABAB1 isoforms localize to distinct synaptic sites and convey separate functions in vivo. At hippocampal CA3-to-CA1 synapses, GABAB1a assembles heteroreceptors inhibiting glutamate release, while predominantly GABAB1b mediates postsynaptic inhibition. Electron microscopy reveals a synaptic distribution of GABAB1 isoforms that agrees with the observed functional differences. Transfected CA3 neurons selectively express GABAB1a in distal axons, suggesting that the sushi repeats, a conserved protein interaction motif, specify heteroreceptor localization. The constitutive absence of GABAB1a but not GABAB1b results in impaired synaptic plasticity and hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions.

Animals↗

Anti-tumor efficacy of a transcriptional replication-competent adenovirus, Ad-OC-E1a, for osteosarcoma pulmonary metastasis.

BACKGROUND: Osteosarcoma (OSA) is the most frequent type of primary malignant bone tumor and is apt to occur in children and young adults. Pulmonary metastasis (OSPM) is the major reason for its fatal outcome. Osteocalcin (OC) is a major noncollagenous bone protein whose expression is limited almost exclusively to bone marrow and osteotropic tumors. OC is also known to express in cell lines with bone metastasis feathers. Gene therapy strategies with the OC promoter directing the replication of adenovirus in a tumor-specific manner are a potential modality for OSPM therapy. METHODS: We detected OC mRNA expression by RNA in situ hybridization in OSA and OSPM samples from patients, and tested OC promoter transcriptional activity in OSA and non-OSA cell lines. Then we used a transcriptional replication-competent adenovirus, Ad-OC-E1a, to treat OSPM, and evaluated its tumor-specific replication and killing activities in vitro as well as anti-OSPM efficacy in vivo via systemic delivery. RESULTS: OC mRNA was detected in all types of OSA tissues, including OSPM tissues. The transcriptional activity of the OC promoter was much higher in a OSPM cell line SAOS-2LM7 and primary OSA cell line MG63 than in non-OSA cell lines, including cell lines from breast cancer, colon cancer, and liver cancer. Ad-OC-E1a expressed E1a protein only in MG63 and SAOS-2LM7, which indicated that adenovirus E1a was under strict control by the OC promoter. Ad-OC-E1a demonstrated killing and viral replication activity close to wild-type adenovirus levels in MG63 and SAOS-2LM7, but the killing and viral replication activities were attenuated significantly in cells expressing low OC transcriptional activity. To test whether Ad-OC-E1a could be used to target human OSPM in vivo, SAOS-2LM7 pulmonary metastasis models in nude mice were induced and treated by tail-vein injection with Ad-OC-E1a. Compared to tumor nodules in the lung in groups treated with PBS or control virus, the quantity of metastasized tumor nodules decreased significantly. Adenovirus-infected cells were stained immunohistochemically only inside and around the OSPM nodules but spared normal lung tissue and other organs. CONCLUSIONS: These data demonstrated that OC promoter could direct adenovirus replication by controlling the E1a gene to target human OSPM in a tumor-specific manner, providing an efficient tool to develop a feasible therapeutic modality for OSPM.

Adenoviridae↗

Combination therapy of androgen-independent prostate cancer using a prostate restricted replicative adenovirus and a replication-defective adenovirus encoding human endostatin-angiostatin fusion gene.

Although prostate-restricted replicative adenovirus has exhibited significant antitumor efficacy in preclinical studies, it is necessary to develop more potent adenoviruses for prostate cancer gene therapy. We evaluated the synergistic killing effect of prostate-restricted replicative adenovirus and AdEndoAngio, a replication-defective adenovirus expressing the endostatin-angiostatin fusion protein (EndoAngio). When coadministered with AdEndoAngio, prostate-restricted replicative adenovirus significantly elevated EndoAngio expression, suggesting that AdEndoAngio coreplicates with prostate-restricted replicative adenovirus. Conditioned medium from prostate cancer cells infected by prostate-restricted replicative adenovirus plus AdEndoAngio inhibited the growth, tubular network formation, and migration of human umbilical vein endothelial cells better than conditioned medium from prostate cancer cells infected by AdEndoAngio alone. Furthermore, in vivo animal studies showed that the coadministration of prostate-restricted replicative adenovirus plus AdEndoAngio resulted in the complete regression of seven out of eight treated androgen-independent CWR22rv tumors, with a tumor nodule maintaining a small size for 14 weeks. The residual single tumor exhibited extreme pathologic features together with more endostatin-reactive antibody-labeled tumor cells and fewer CD31-reactive antibody-labeled capillaries than the AdEndoAngio-treated tumors. These results show that combination therapy using prostate-restricted replicative adenovirus together with antiangiogenic therapy has more potent antitumor effects and advantages than single prostate-restricted replicative adenovirus and deserves more extensive investigation.

Adenoviridae↗

[Association between vitamin D receptor gene polymorphism and vitamin D deficiency rickets].

OBJECTIVE: To explore the genetic susceptibility of children to vitamin D deficiency rickets through studying the association between Vitamin D receptor (VDR) gene polymorphism and vitamin D deficiency rickets. METHODS: One hundred and fifty-nine children (100 boys and 59 girls, aged 0 to 2 years), with new-onset vitamin D deficiency rickets were enrolled. The patients sampled from a community of Jiamusi City, Heilongjiang Province. Seventy-eight healthy age-matched children (46 boys and 32 girls) were used as the controls. VDR gene polymorphism (cleaved by restriction endonuclease Fok I) was analyzed by polymerase chase reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the VDR genotype and allele were compared between the two groups. RESULTS: The frequencies of FF, Ff and ff genotypes were 37%, 51% and 12% in the Rickets group, and 18%, 55% and 27% in the Control group. A significant difference was found in the frequency distribution of the VDR genotype between the two groups (chi(2)(0.01(2))=9.210, chi(2)=13.3880, P < 0.01). In the Rickets group, f allele frequency was lower (37% vs 54%), while the F allele was more common than the Control group (63% vs 46%). CONCLUSIONS: There is an association between the VDR gene Fok I polymorphism and vitamin D deficiency rickets. The individuals with the F allele are more susceptible to vitamin D deficiency rickets.

Female↗

[Levels of serum brain natriuretic peptide in children with congestive heart failure or with severe pneumonia].

OBJECTIVE: Some research has shown that B-type brain natriuretic peptide (BNF) is helpful in differentiating cardiac from pulmonary etiologies of dyspnea in adults. This study was designed to investigate whether BNP concentration could be similarly applied in children presenting with dyspnea. METHODS: Blood samples were collected from 65 children presenting with dyspnea, due to congestive heart failure (CHF, n=24), pneumonia (n=23) or pneumonia together with CHF (n=18). The samples from 15 healthy children were used as the controls. There were no significant differences in age among the four groups. Serum BNP levels were measured using ELISA. RESULTS: Serum BNP levels in the CHF group (141.55 +/- 75.99 pg/mL) were significantly higher than those in the Pneumonia group (26.00 +/- 14.57 pg/mL; P < 0.01), and the Pneumonia together with CHF group (113.73 +/- 87.05 pg/mL; P < 0.05), as well as the Control group (19.31 +/- 10.30 pg/mL; P < 0.01). The patients with pneumonia together with CHF had significantly higher serum BNP levels than those of the Pneumonia and the Control groups (P < 0.01). There were no significant differences in BNP levels between the Pneumonia and the Control groups. The area under the receive operator characteristic (ROC) curve, which demonstrated the diagnostic utility of BNP in differentiating CHF from pneumonia, was 0.978 (P < 0.01). At a cut-off of 49 pg/mL, BNP had a sensitivity of 87.5% and a specificity of 95.8% for differentiating CHF from pneumonia. In the 18 patients who were diagnosed with pneumonia together with CHF, 11 had BNP levels above 49 pg/mL. The mean levels of BNP of the 11 patients were significantly higher than those of the patients with pneumonia (172.08 +/- 56.47 pg/mL vs 25.00 +/- 14.57 pg/mL; P < 0.01) but were significantly decreased after treatment (26.12 +/- 15.71 pg/mL; P < 0.01). CONCLUSIONS: BNP level is of value in differentiating cardiac from pulmonary causes of dyspnea in children. BNP level is also helpful in assessing whether or not severe pneumonia couples with heart failure in children.

Child, Preschool↗

[Molecular background of weak D type 15 as the predominant weak D type found in Chinese population].

This study was aimed to investigate the molecular genetic basis and serological phenotype of Rh weak D type 15 individuals. Samples were identified by serological tests and genotyped by sequence specific primer-PCR (SSP-PCR), and were sequenced to detect the changes of all ten RHD exons. The number of gene RHD was detected through SSP-PCR. The results showed that in tested individuals of weak D type confirmed by the IAT, 18 cases (56% in weak D) were weak D type 15. Rh factors found in 2 weak D type 15 individuals (11%) were C+c+E+e; Rh factors found in 2 weak D type 15 individuals (11%) were C+c+E-e+; others (78%) were c-c+E+e+. The results by serological tests were consistent with the results genotyped by PCR-SSP method. In all 18 samples, the sequencing result revealed a gene mutation 845G > A at the exon 6 of the RHD and the point mutation changed amino acid G282D of the RhD polypeptide. The zygosity test demonstrated that 2 out of 18 weak D type 15 individuals were RHD(+)/RHD(+) homozygous (two DCe/DcE), 16 cases were RHD(+)/RHD(-) heterozygous (two DCe/dce and fourteen DcE/dce). It is concluded that Weak D type 15 is predominant in weak D individuals of Chinese Han Nationality, and most of them are heterozygous with various RH haplotypes.

Asian People↗

Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer.

PSES is a chimeric enhancer containing enhancer elements from prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) genes that are prevalently expressed in androgen-independent prostate cancers. PSES shows strong activity equivalent to cytomegalovirus (CMV) promoter, specifically in PSA/PSMA-positive prostate cancer cells, the major cell types in prostate cancer in the absence of androgen. We developed a recombinant adenovirus (AdE4PSESE1a) by placing adenoviral E1a and E4 genes under the control of the bidirectional enhancer PSES and enhanced green fluorescent protein gene for the purpose of intratumoral virus tracking under the control of CMV promoter. Because of PSES being very weak in nonprostatic cells, including HEK293 and HER911 that are frequently used to produce recombinant adenovirus, AdE4PSESE1a can only be produced in the HER911E4 cell line which expresses both E1 and E4 genes. AdE4PSESE1a showed similar viral replication and tumor cell killing activities to wild-type adenovirus in PSA/PSMA-positive prostate cancer cells. The viral replication and tumor cell killing activities were dramatically attenuated in PSA/PSMA-negative cells. To test whether AdE4PSESE1a could be used to target prostate tumors in vivo, CWR22rv s.c. tumors were induced in nude mice and treated with AdE4PSESE1a via intratumoral and tail vein injection. Compared to tumors treated with control virus, the growth of CWR22rv tumors was dramatically inhibited by AdE4PSESE1a via tail vein injection or intratumoral injection. These data show that adenoviral replication can be tightly controlled in a novel fashion by controlling adenoviral E1a and E4 genes simultaneously with a single enhancer.

Adenoviridae↗

Effect of the 1,450 nm diode non-ablative laser on collagen expression in an artificial skin model.

BACKGROUND AND OBJECTIVE: The 1,450-nm Smoothbeam Laser is a diode laser equipped with a cryogen cooling spray. Primary objectives were to evaluate the effects of this non-ablative laser on Apligraf (bioengineered skin-substitute) and to document its use as a model for non-ablative procedures. We also measured the effects of laser fluence levels on collagen and elastin expression. STUDY DESIGN/MATERIALS AND METHODS: Three sheets of Apligraf were used for this study. Each received six separate laser applications at 4J, 6J, 8J, 10 J, 12J, and 14J. The sheets were then incubated with 10% CO(2) at 37 degrees C and samples were collected and analyzed 3 days later, using RT-PCR and immunofluorescent staining. RESULTS: Collagen III expressions significantly increased in both mRNA and protein levels at approximately 12 J. CONCLUSIONS: There appears to be a threshold effect where there is very little increased collagen III mRNA and protein expression until the laser fluence reaches around 12J.

Collagen↗

Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by alpha-lactalbumin promoter.

The breast-specific antigen alpha-lactalbumin is expressed in >60% of breast cancer tissues. To evaluate the effect of gene therapy for breast cancer by controlling adenovirus replication with human alpha-lactalbumin promoter, we investigated the activity of a 762-bp human alpha-lactalbumin promoter. Alpha-lactalbumin promoter showed significantly higher activity in MDA-MB-435S and T47D breast cancer cells than in normal breast cell lines or other tumor cell lines. We then developed two novel breast cancer-restricted replicative adenoviruses, AdALAE1a and AdE1aALAE1b. In AdALAE1a, expression of adenoviral E1a gene is under the control of alpha-lactalbumin promoter, and in AdE1aALAE1b, expression of both E1a and E1b genes is under the control of a single alpha-lactalbumin promoter. Both breast cancer-restricted replicative adenoviruses showed viral replication efficiency and tumor cell-killing capability similar to wild-type adenovirus in MDA-MB-435S and T47D cells. The replication efficiency and tumor cell-killing capability of both viruses were attenuated significantly in cells that did not support alpha-lactalbumin promoter. AdE1aALAE1b showed better breast cancer-restricted replication than AdALAE1a, suggesting that a transcriptional targeting modality with alpha-lactalbumin promoter controlling both E1a and E1b gene expression is superior to alpha-lactalbumin promoter controlling only E1a gene expression. Importantly, we found that AdE1aALAE1b could be used to target hormone-independent breast tumors in vivo by inhibiting the growth of MDA-MB-435S s.c. tumors. These data showed that alpha-lactalbumin promoter could regulate the replication of adenovirus to target hormone-independent breast cancers, suggesting that alpha-lactalbumin promoter can be used to develop a novel therapeutic modality for hormone-independent breast cancer.

Adenoviridae↗

[Analysis of genetic polymorphism in randomized donor's HPA 1-16 antigens and establishment of typed platelet donor data bank].

To study the genetic polymorphism of HPA 1-16 platelet antigen alleles among unrelated volunteer donors and establish a typed platelet donor panel in Handan, typing was perfomed by polymerase chain reaction using sequence-specific primers (SSP-PCR); 148 random unrelated blood donors in Handan were genotyped for each of the HPA 1-16 antigen. The gene frequencies were analyzed and the genetype frequencies were determined by direct counting, and these data were compared with HPA distribution among various population by the chi-square test. The results indicated that HPA-1a, 2a, 4a-14a, 16a genes were found among the 16 HPAs in every sample tested. Monomorphic HPA-4a, 7a-14a, 16a were found in the samples. For HPA-1, 2, 5 and 6, a/a homozygosity was predominant with frequencies of 0.9595, 0.8108, 0.9865, 0.9797, respectively, and none of HPA b/b was found in the samples. HPA-1b, 2b, 5b, 6b were rarely found among subjects. HPA-15 had the greatest heterozygosity with a gene frequency of 0.2230, 0.5270, 0.2500 for HPA15a/15a, HPA15a/15b, HPA15b/15b, respectively. HPA-3 showed the second greatest heterozygosity with a gene frequency of 0.3851, 0.5135, 0.1014 for HPA3a/3a, HPA3a/3b, HPA3b/3b, respectively. HPA genotype frequencies showed a good fit to Hardy-Weinberg equilibrium. HPA1-5 gene frequencies for Chinese people in Handan were consistent with those of Chinese people in Shijiazhuang (P > 0.05). Among the HPA1-13, -15, the frequencies of HPA-1, -2, -6 for Chinese people in Handan differed appreciably from those for Chinese people in Taiwan (P < 0.05), others were similar to those of Chinese people in Taiwan. Among the HPA 1 - 8, a similarity was noted between Chinese people in Handan and Koreans (P > 0.05), except for HPA-3. Frequencies of HPA-1, -2, -5 significantly were differed from those in African Americans, as compared with HPA 1-5 (P < 0.05). Comparison of gene frequencies from HPA-1 and -5 showed significant differences between Chinese people in Handan and people in UK (P < 0.05). It is concluded that HPA-2, -3, -5, -15 of people in Western region of China have polymorphism, incompatible frequency of HPA antigen distribution is higher, which inevitably results in the increase of immunologic exposure, therefore attention must be paid to the importance of HPA-2, -3, -5, -15 in clinical disorders. This study for the first time completely analyses HPA1-16 gene frequencies in China, and provides data for establishing a typed platelet donor panel in Handan, China.

Antigens, Human Platelet↗

Understanding the unique characteristics of suicide in China: national psychological autopsy study.

OBJECTIVE: To compare the characteristics of suicides in the four main demographic groups: urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China. METHODS: A detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country. RESULTS: Pesticide ingestion accounted for 58% (519) of all suicides and 61% (318/519) of deaths were due to unsuccessful medical resuscitation. A substantial proportion (37%) of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% (76/563) received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion (79%), the lowest prevalence of mental illness (39%), and the highest acute stress from precipitating life events just prior to the suicide. CONCLUSION: Many suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.

Adolescent↗

[Rescue operations of the recurrent nasal and paranasal sinus neoplasms].

OBJECTIVE: To investigate the symptoms, factors relating to recurrences, the styles of the rescue operation and the reconstructive methods of the surgical defects in patients with recurrent nasal and paranasal sinus neoplasms. METHODS: Excluding the primary neoplasm, only patients with recurrent tumors and suitable for rescue operations entered the group. Kaplan-Meier method was used to estimate the survival probability. RESULTS: Twenty-five patients receiving rescue operations from 1993 to 2002 who met the above inclusion criteria were reviewed. The age ranged from 13 - 66 years. All the patients had once surgery or radiation therapy at least. The time between the last treatments and the recurrences ranged from 2 weeks to 46 months. 80 per cent of the recurrences were within the first 2 years after the last therapy. The recurrent symptoms included headache (10 patients), eminences in or around the operation fields (9 patients), diminution of vision (7 patients), and so on. The patients were followed 1 to 65 months. There were no patients died during the rescue operations. Five patients were alive without recurrences and 3 alive with local or regional recurrences. Thirteen died of local recurrences and 1 died of metastasis to lung. The one-year, 2-year and 3-year survival rate were 62.5%, 43.7% and 29.1%, respectively. The median survival time was 18 months. Complications included cerebrospinal rhinorrhea (3 patients), central diabetes insipidus (1 patient) and necrosis of part of the flap (1 patient). CONCLUSIONS: Most of the local recurrences occur within 2 years after the last therapies. The recurrent symptoms are commonly headache and eminences in or around the operation fields. The recurrences are closely related to pathological types and differential degrees of the neoplasms. The reasonable and timely combined treatment may help to decrease the frequencies of the recurrences. The rescue operations with effective methods can improved the patients' life qualities and lengthen their life spans. The main complications are cerebrospinal rhinorrhea most of which can be cured by conservative treatment.

Adolescent↗

Laminin-10 is crucial for hair morphogenesis.

The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (alpha5beta1gamma1) in hair follicle development. Laminin-10 was present in the basement membrane of elongating hair germs, when other laminins were downregulated, suggesting a role for laminin-10 in hair development. Treatment of human scalp xenografts with antibodies to laminin-10, or its receptor beta1 integrin, produced alopecia. E16.5 Lama5 -/- mouse skin, lacking laminin-10, contained fewer hair germs compared with controls, and after transplantation, Lama5 -/- skin showed a failure of hair germ elongation followed by complete hair follicle regression. Lama5 -/- skin showed defective basement membrane assembly, without measurable increases in anoikis. Instead, Lama5 -/- skin showed decreased expression of early hair markers including sonic hedgehog and Gli1, implicating laminin-10 in developmental signaling. Intriguingly, treatment of Lama5 -/- skin with purified laminin-10 corrected basement membrane defects and restored hair follicle development. We conclude that laminin-10 is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect.

Alopecia↗

Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix.

Angiogenesis is critical to wound repair. Newly formed blood vessels participate in provisional granulation tissue formation and provide nutrition and oxygen to growing tissues. In addition, inflammatory cells require the interaction with and transmigration through the endothelial basement membrane to enter the site of injury. Angiogenesis, in response to tissue injury, is a dynamic process that is highly regulated by signals from both serum and the surrounding extracellular matrix (ECM) environment. Vascular endothelial growth factor, angiopoietin, fibroblast growth factor, and transforming growth factor beta are among those most potent angiogenic cytokines in wound angiogenesis. The cooperative regulation of them is essential for wound repair. Migration of endothelial cells and development of new capillary vessels during wound repair is dependent on not only the cells and cytokines present but also the production and organization of ECM components both in granulation tissue and in endothelial basement membrane. The ECM regulates angiogenesis by providing scaffold support and signaling roles. They also serve as a reservoir and modulator for growth factors. Laminins are the major noncollagenous ECM of endothelial basement membrane. Two newly recognized laminins, 8 and 10, are the major laminins produced by human dermal microvascular endothelial cells. Laminin 10 is highly expressed in blood vessels around skin wounds. Laminin 8 promotes dermal endothelial cell attachment, migration, and tubule formation. Integrins with either beta 1 or alpha v subunits are the major cellular surface receptors for ECM molecules and mediate the interactions between cells and ECM during wound angiogenesis.

Cytokines↗

[Evaluation on the accuracy of reported suicides in the Chinese population].

OBJECTIVE: To evaluate the accuracy of reports of suicide in the national death registry systems and to estimate a more accurate suicide rate. METHODS: Twenty-three sites from the Disease Surveillance Points Network-one of the national death registry systems-were selected and 1 932 of the deaths that occurred at these sites from August 1995 through August 2000 in which the official cause was classified as "accidental" or "mental illness" were selected for detailed household surveys focusing on reassessing the cause of death. Valid interviews were completed in 1 653 of these cases. The original cause of death recorded on the death certificate was compared with the finding of the detailed household survey and the result was used to adjust the suicide rate. RESULTS: After detailed investigation, 16 of the 857 (1.87%) deaths reported on the death certificate as suicide were considered accidental deaths, 39 of the 721 (5.41%) accidental deaths were considered suicide, 17 of the 35 (48.57%) cases reported as undetermined accidents were considered suicide, and 6 of the 40 (15.00%) cases in which mental illness was the recorded cause of death were considered suicide. After adjustments for errors in the reported cause of death and for missing deaths, the reported crude suicide rate of 13.65/100 000 in China was adjusted to 22.99/100 000 (95% CI: 21.78/100 000 - 24.25/100 000). CONCLUSION: After adjustments the actual suicide rate for China was higher than the reported rate indicating that suicide was an increasingly important public health problem for China.

China↗

Replication efficiency and sequence analysis of full-length hepatitis B virus isolates from hepatocellular carcinoma tissues.

Prolonged replication of hepatitis B virus (HBV) in liver tissues of hepatitis B patients has been considered as an important risk factor for the development of malignancy. Few studies on full-length HBV sequencing in association with the replication efficiency of isolates from HCC tissues have been reported. To study the structural and functional genomics of HBV isolates from Chinese hepatocellular carcinoma (HCC) patients, full-length HBV genomes were amplified from 6 HBV-marker positive HCC tissues and used to transfect HepG2 cells. Five of 6 isolates showed high replicative efficiency. All isolates were of genotype C and "hot-spots" mutations were detected in the B cell and T helper (Th) cell epitopes of the envelope and the core region. In addition, the X region of 2 isolates contained a stop-codon mutation that was predicted to result in a truncated X protein. High replicative HBV immune escape mutants that persist in infected hepatocytes could be 1 of the important factors to initiate pathological processes for the development of HCC in Chinese patients.

Base Sequence↗