Survey on the Construction Status of Forensic Virtual Autopsy Laboratory and the Applicability of Laboratory Accreditation.

OBJECTIVES: To survey the development status and actual needs of virtual autopsy technology in China and to clarify the applicability of forensic virtual autopsy laboratory accreditation. METHODS: The questionnaire was set up included three aspects：(1) the current status of virtual autopsy technology development; (2) the accreditation elements such as personnel, equipment, entrustment and acceptance, methods, environmental facilities; (3) the needs and suggestions of practicing institutions. A total of 130 forensic pathology institutions were surveyed by online participation through the Questionnaire Star platform. RESULTS: Among the 130 institutions, 43.08% were familiar with the characteristics of virtual autopsy technology, 35.38% conducted or received training in virtual autopsy, and 70.77% have establishment needs (including maintenance). Relevant elements were suitable for laboratory accreditation. CONCLUSIONS: Virtual autopsy identification has gained social recognition. There is a demand for accreditation of forensic virtual autopsy laboratory. After the preliminary assessment, considering the characteristics and current situation of this technology, China National Accreditation Service for Conformity Assessment (CNAS) can first carry out the accreditation pilot of virtual autopsy project at large comprehensive forensic institutions with higher identification capability, and then CNAS can popularize the accreditation in a wide range when the conditions are suitable.

The Predictive Potential of Altered Voxel-Based Morphometry in Severely Obese Patients With Meibomian Gland Dysfunction.

Objective: To investigate voxel-based morphometry (VBM) by using magnetic resonance imaging (MRI) in meibomian gland dysfunction patients with severe obesity (PATs) and to explore the application of VBM in the early diagnosis, prevention of cognitive impairment and targeted treatment of this disease. Methods: Sixteen PATs and 12 healthy controls (HCs) were enrolled and underwent MRI. Whole-head images were analyzed using VBM and data were compared between groups using an independent samples t-test. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic value of this approach. Mini-mental state examination (MMSE) scores were used to assess cognitive impairment and were analyzed using an independent samples t-test. Results: Compared with HCs, the VBM values in PATs were reduced in the left cerebellum and right thalamus but increased in the right brainstem, right precuneus and right paracentral lobule. The results of ROC curve analysis indicated that VBM may be useful in meibomian gland disease diagnosis. Comparison of MMSE scores between groups showed mild cognitive impairment in PATs. Conclusion: PATs showed altered VBM values in some brain areas. These findings may provide information about the pathophysiology of meibomian gland dysfunction and may help to explain the underlying mechanisms of clinical manifestations in PATs, such as cognitive impairment. Abnormal VBM values in these brain areas may serve as predictive factors for development of meibomian gland disease in severely obese people and as indicators for individualized treatment.

Identification of Haplotype Tag Single-Nucleotide Polymorphisms within the PPAR Family Genes and Their Clinical Relevance in Patients with Major Trauma.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) play important roles in the development of inflammatory diseases and sepsis. Recently, genetic variants of PPARs genes have been widely studied in some inflammatory diseases. However, the association between PPAR family of genes polymorphisms and sepsis risk in trauma patients was little known. METHODS: SNPs were selected from the PPARs genes through constructing haplotype blocks and genotyped by the improved multiplex ligation detection reaction (iMLDR) method. The association between the selected SNPs and the risk of sepsis and multiple organ dysfunction (MOD) scores was evaluated in 734 trauma patients. In addition, tumor necrosis factor α (TNFα) production of peripheral blood leukocytes was also analyzed after lipopolysaccharide (LPS) stimulation. RESULTS: Our results revealed that there were significant associations between the rs10865710 polymorphism and the risk of sepsis and MOD scores in Chinese Han trauma patients. Further, we found that the level of TNFα production was higher in patients with the rs10865710 G allele compared to those with the variant C allele. CONCLUSIONS: The rs10865710 polymorphism in the PPARγ gene might be used to assess the risk of sepsis and multiple organ dysfunction syndrome (MODS) in trauma patients.

The Penumbra System for the Treatment of Acute Ischemic Stroke: Report of Two Cases.

Mortality associated with the occlusion of large vessels in acute ischemic stroke is particularly high despite best available medical therapy. Early and safe revascularization of the primary occlusion is correlated with good clinical result. We report two patients with acute ischemic stroke in whom the mechanical device Penumbra System was used for thrombolysis and embolectomy. The Penumbra System provided the revascularization of the primary occlusion site in the two patients and complete revascularization was obtained. Improvement was observed in both cases on the National Institutes of Health Stroke Scale and on modified Rankin scale scores at 1 and 30 days post-procedure. Neither of the patients had intracranial hemorrhage. The Penumbra System is a valuable device as a treatment for acute ischemic stroke secondary to large vessel occlusion.

Association between the TLR2 Arg753Gln polymorphism and the risk of sepsis: a meta-analysis.

INTRODUCTION: Recently, researchers in a number of studies have explored the association between the Toll-like receptor 2 (TLR2) Arg753Gln polymorphism and sepsis risk. However, the results were conflicting. In this meta-analysis, we aimed to confirm the effect of the TLR2 Arg753Gln polymorphism on sepsis risk. METHODS: Relevant records up to 1 June 2015 were retrieved from the PubMed, Embase, and Web of Knowledge databases. The odds ratios with their corresponding 95 % confidence intervals were used to assess the association between the TLR2 Arg753Gln polymorphism and sepsis risk. The selection of a fixed or random effects model was made according to a heterogeneity test in total and subgroup analyses. Sensitivity analysis and publication bias test were performed to ensure the reliability of our results. RESULTS: A total of 12 studies with aggregate totals of 898 cases and 1517 controls met our inclusion criteria for meta-analysis. There were significant associations between the TLR2 Arg753Gln polymorphism and sepsis risk in overall analyses under two genetic models (the allele comparison and the dominant model). In addition, subgroup analyses based on age group, ethnicity, sepsis type, and source of control also showed a significant effect of the TLR2 Arg753Gln polymorphism on sepsis risk. CONCLUSIONS: Our present meta-analysis supports a direct effect of the TLR2 Arg753Gln polymorphism on sepsis risk, especially in Europeans. The TLR2 Arg753Gln polymorphism might be used as a relevant risk estimate for the development of sepsis. Studies with larger sample sizes and homogeneous groups of patients with sepsis are required for further analysis.

Identification of haplotype tag single nucleotide polymorphisms within the nuclear factor-κB family genes and their clinical relevance in patients with major trauma.

INTRODUCTION: Nuclear factor-κB (NF-κB) family plays an important role in the development of sepsis in critically ill patients. Although several single nucleotide polymorphisms (SNPs) have been identified in the NF-κB family genes, only a few SNPs have been studied. METHODS: A total of 753 patients with major blunt trauma were included in this study. Tag SNPs (tSNPs) were selected from the NF-κB family genes (NFKB1, NFKB2, RELA, RELB and REL) through construction of haplotype blocks. The SNPs selected from genes within the canonical NF-κB pathway (including NFKB1, RELA and REL), which played a critical role in innate immune responses were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and multiple organ dysfunction (MOD) syndrome. Moreover, the rs842647 polymorphism was analyzed in relation to tumor necrosis factor α (TNF-α) production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. RESULTS: Eight SNPs (rs28362491, rs3774932, rs4648068, rs7119750, rs4803789, rs12609547, rs1560725 and rs842647) were selected from the NF-κB family genes. All of them were shown to be high-frequency SNPs in this study cohort. Four SNPs (rs28362491, rs4648068, rs7119750 and rs842647) within the canonical NF-κB pathway were genotyped, and rs842647 was associated with sepsis morbidity rate and MOD scores. An association was also observed between the rs842647 A allele and lower TNF-α production. CONCLUSIONS: rs842647 polymorphism might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.

Association between IL-6-174G/C polymorphism and the risk of sepsis and mortality: a systematic review and meta-analysis.

BACKGROUND: Recent studies have reported the association between IL-6-174G/C polymorphism and sepsis. However, the results are inconclusive and conflicting. To better understand the role of IL-6-174G/C polymorphism in sepsis, we conducted a comprehensive meta-analysis. METHODOLOGY: Literature search was conducted through PubMed, Embase, Web of Knowledge databases until July 29, 2013. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effect model based on heterogeneity test in total and subgroup analyses. RESULTS: Twenty studies on the risk of sepsis and seven studies on sepsis mortality were included. None of the results showed evidence of a significant association between IL-6-174G/C polymorphism and sepsis risk in overall analysis or subgroup analyses based on sepsis type, ethnicity, source of control and age under any genetic model (the allele comparison, the codominant, the recessive or the dominant model). Although there was a statistically significant association between IL-6-174 G/C polymorphism and sepsis-related mortality under the recessive model, the significance did not exist after Bonferroni's correction. CONCLUSIONS: Current evidence does not support a direct effect of IL-6-174 G/C polymorphism on the risk of sepsis. In addition, there was no association between IL-6-174 G/C polymorphism and sepsis mortality after Bonferroni's correction. Further analyses of gene-environment interactions and more studies based on larger sample size and homogeneous sepsis patients are required.

A deeper understanding of the association between CTLA4 +49A/G and acute rejection in renal transplantation: an updated meta-analysis.

To reevaluate the association between the costimulatory molecule cytotoxic T lymphocyte-associated antigen4 (CTLA4) single nucleotide polymorphism (SNP) +49A/G and acute rejection (AR) in renal transplantation, nine studies published before June 2013 were analyzed. Meta-analysis and cumulative meta-analysis (metacum) were performed for each genotype in a random/fixed effect model. The combined odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. In the sensitivity analysis, a single study involved in the meta-analysis was deleted each time to investigate the influence of the individual data sets on the pooled ORs. Meta-analysis regression was used for some influence factors, such as year of publication, total number in each group (AR group and control group), ethnicity, the ratio of GG to GA + AA, the ratio of G to A in CTLA4 +49A/G. Overall, a significant correlation was noted between the CTLA4 SNP (+49A/G) and the risk of AR (for GG vs. AG + AA: OR = 1.35, 95% CI = 1.05-1.73, p = 0.02; for G vs. A: OR = 1.21, 95% CI = 1.03-1.42, p = 0.02), especially in the Asian subgroup (for GG vs. AG + AA: OR = 1.79, 95% CI = 1.15-2.78, p = 0.009; for G vs. A: OR = 1.47, 95% CI = 1.04-2.07, p = 0.03). Of the influence factors, the ratio of GG to GA+AA (p = 0.046) and the ratio of G to A (p = 0.017) were significant factors. In conclusion, our results suggest that CTLA4 +49A/G contribute to the risk of AR following renal transplantation.

Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis.

BACKGROUND: Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. METHODS: Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. RESULTS: Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). CONCLUSIONS: Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings.

[Multiple mechanisms of depression].

Depression is a grievous mental disease with an increasing high morbidity year by year and a serious social harm. The pathogenesises of depression is complicated and involves with multi-mechanisms and multi-organs. Recent studies demondtrate that in the nerval system and endocrine system there are many types of neurotransmitters and hormones, as well as their receptors, involved in depression. This paper reviews the research progress of depression in recent years.

The impact of sulfonylureas on tacrolimus apparent clearance revealed by a population pharmacokinetics analysis in Chinese adult liver-transplant patients.

AIMS: The aims of this study were to determine the population pharmacokinetics of tacrolimus in Chinese adult liver-transplant recipients and to identify factors that may account for this variability. METHODS: Tacrolimus dose and blood concentrations, along with clinical data, were collected retrospectively from 262 liver-transplant recipients. Data were analyzed using a nonlinear mixed-effects modeling method. A 1-compartment model with first-order absorption and elimination was selected as the base model. The influence of the following parameters were explored: (1) demographic characteristics, (2) biochemical and hematological laboratory test results, (3) surgery parameters, and (4) commonly used comedications. RESULTS: The typical values (interindividual variability percent coefficient of variation) for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 20.9 L h (23.8%) and 808 l (70.4%), respectively. The residual variability was 33.6%. Finally, the 4 covariates that showed a strong correlation with CL/F in this study were daily dose, hematocrit, total plasma protein, and the coadministration of sulfonylureas. CL/F was reduced significantly with sulfonylureas cotherapy, higher hematocrit levels, and elevated total protein. Moreover, CL/F increased nonlinearly with larger daily doses of tacrolimus. CONCLUSIONS: Concurrent therapy with sulfonylureas influenced tacrolimus CL/F in liver transplantation patients. These results and model will help clinicians to optimize tacrolimus regimens in Chinese liver transplantation patients.

Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients.

Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A, rs3087243G/A) on the early acute rejection (AR) of Chinese deceased donor renal transplantation recipients. Genotyping of the CTLA4 SNPs was performed in 167 deceased donor renal transplantation recipients. Each patient underwent a 6-month follow-up observation for AR. The incidence of AR during the 6 months post-transplantation was 26.9% (45 out of 167 patients). Patients experiencing AR were found to have a higher frequency of the rs733618TT genotype and T allele (p=0.000 and p=0.002, respectively). While the haplotype CACAG was merely observed in non-AR group (corrected p=0.000), the frequency of haplotype TACGG was significantly higher in AR group than in non-AR group even after 50,000 permutation tests (corrected p=0.018). In conclusion, these polymorphisms statistically significantly associated with acute renal allograft rejection may be considered as a risk factor of AR in Chinese renal transplantation recipients except for haplotype CACAG as a protective one.

Hypoxia-induced up-regulation of aquaporin-1 protein in prostate cancer cells in a p38-dependent manner.

BACKGROUND/AIMS: Aquaporin-1 (AQP1) is a glycoprotein that mediates osmotic water transport, its expression has been found to correlate with tumour stage in some tumours. However, the mechanism by which AQP1 protein expression is regulated in tumor cells remains to be fully elucidated. We hypothesized that hypoxia might play an important role in AQP1 induction during tumorigenesis and at the late stages of tumor development. METHODS: Isotonic and serum-free hypoxic models were used to investigate AQP1 expression in PC-3M human prostate cancer cells. RESULTS: AQP1 expression was up-regulated by density-induced pericellular hypoxia and cobalt(II) chloride (CoCl(2))-induced hypoxia at the transcriptional level. Moreover, phosphorylation of p38 mitogen-activated protein kinase (MAPK) was induced by density-induced pericellular hypoxia and CoCl(2)-induced hypoxia, specific inhibitors of p38 MAPK could concentration-dependently block those effects of hypoxia on AQP1 expression. Intracellular calcium ion (Ca(2+)) and protein kinase C (PKC) were shown to be responsible for the activation of p38 MAPK pathway. In addition, AQP1 induction in dense cultures was dependent on lowered oxygen (O(2)) tension. In high cell density culture, certain secretory proteins might induce AQP1 expression indirectly. CONCLUSION: These findings suggest that AQP1 could be induced by hypoxia at transcription level, and the regulation of AQP1 in PC-3M cells is dependent on calcium, PKC and p38 MAPK, as well as low oxygen tension.

[Isolating sperm cells by laser capture microdissection technique from mixture sample].

OBJECTIVE: To assess the application value of laser capture microdissection (LCM) technique for isolating a small number of sperm cells from mixture sample. METHODS: Mixture samples were prepared with sperm cells and vaginal epithelia at different concentrations. Both LCM technique and the differential lysis method were employed to obtain sperm cells from the mixture samples, and DNA was extracted by magnetic beads method. STR genotyping was determined using Identifiler kit. RESULTS: The successful STR genotype rate of sperm cells isolated from mixture samples with LCM technique was 92.86% (13/14). The rate of differential lysis method was 7.14% (1/14). The successful rates between the two methods were statistically different (P < 0.05). CONCLUSION: LCM technique can effectively exclude the interference of female cell component and isolate a small number of sperm cells to obtain a single male STR genotyping. LCM technique is obviously better than the differential lysis method.

Simultaneous determination of mycophenolic acid and its metabolites by HPLC and pharmacokinetic studies in rat plasma and bile.

In this study, we determined the pharmacokinetics of mycophenolic acid (MPA) and its metabolites mycophenolic acid glucuronide (MPAG) and acyl glucuronide (AcMPAG) in rat plasma and bile, using a newly developed HPLC method. Protein precipitation and liquid-liquid extraction were employed in sample preparation of plasma and bile, respectively. The HPLC methods included a gradient elution consisting of acetonitrile and phosphate buffer at a flow rate of 1.2 mL/min, with UV detection at 254 nm. The HPLC method was found to be sensitive and linear (r(2) ≥ 0.9991, 1.0-128.0 and 0.25-32.0 mg/L for MPA; 1.0-128.0 and 0.5-64.0 mg/L for MPAG; 0.25-32.0 and 1.0-128.0 mg/L for AcMPAG in rat plasma and bile, respectively), precise (both the intra- and inter-day variability were ≤ 6.8%), and accurate (both the intra- and inter-day accuracy were between 92.2% and 105.4%). The average extraction efficiencies for MPA, MPAG and AcMPAG were 85.3%, 100.1%, and 94.7% in plasma, and 88.0%, 67.3%, and 68.3% in bile, respectively. The method was successfully employed for pharmacokinetic studies in plasma and bile after oral administration of mycophenolate mofetil (prodrug of MPA) in rats.

Population pharmacokinetic study of cyclosporine based on NONMEM in Chinese liver transplant recipients.

A population pharmacokinetic study of cyclosporine (CsA) was performed in liver transplant recipients. A total of 3731 retrospective drug monitoring data points at predose (C0) and 2 hours postdose (C2) were collected from 124 liver transplant recipients receiving CsA microemulsion. Population pharmacokinetic analysis was performed using the program NONMEM (nonlinear mixed-effect modeling). Various covariates potentially related to CsA pharmacokinetics were explored, and the final model was validated by a bootstrap method and by assessing the predictive performance using empiric Bayesian estimates. A one-compartment model with first-order absorption was considered. Population parameters of apparent clearance (CL/F) and volume of distribution were estimated as 23.1 L/h and 105 L, respectively. CL/F was influenced by four covariates: duration of CsA therapy (DT), hematocrit (HCT), and concurrent prednisone dose (PR). The final model for CL/F was fitted as follows: CL/F = 23.1 + 0.5 × (DT/200) - 0.07 × HCT + 0.04 × PR. The interindividual variability in CL/F, volume of distribution, and Ka calculated as coefficient of variation were 15.1%, 9.3%, and 66.0%, respectively. The intraindividual variability was 18.6%. The model fitted well with the observed data, and the bootstrap method guaranteed robustness of the population pharmacokinetic study model. Model validation was performed by a visual predictive check. Moreover, simulation was conducted to facilitate the individualized treatment based on patient information and the final model. The model to characterize population pharmacokinetic study of CsA provided better clinical individualization of CsA dosing in liver transplant recipients based on patient information and to assess patients' suitability for CsA therapy.

[Study on the distribution of sub-genotype B on hepatitis B virus in patients with chronic HBV infection from 4 cities of China].

OBJECTIVE: To investigate the distribution of sub-genotype B on hepatitis B virus (HBV) in patients with HBV chronic infection from 4 cities (Beijing, Shijiazhuang, Wenzhou and Shenzhen) of China. METHODS: A type-specific nested polymerase chain reaction(PCR) with multiplex pairs of primers was used for HBV genotyping,and Ba and Bj sub-genotypes were identified by a PCR-restriction fragment length polymorphism (PCR-RFLP) method. A total of 101 serum samples collected from patients with chronic HBV/B infection were detected. Among them, 18 were collected from Beijing, 22 from Shijiazhuang, 34 from Wenzhou and 27 from Shenzhen. Thirty from the 101 serum samples were randomly selected and analyzed by PCR product sequencing. RESULTS: All of the 101 serum samples were identified as sub-genotype Ba,and none of them was sub-genotype Bj. CONCLUSION: Sub-genotype Ba was a predominant strain of HBV/B in patients with chronic HBV infection from these 4 cities.

[Establishment of a semi-nested PCR for identifying the sub-genotypes (Ba and Bj) of hepatitis B virus of genotype B].

OBJECTIVE: To establish a sensitive, specific, simple and practicable method for identifying the two sub-genotypes (Ba and Bj) of genotype B isolates of hepatitis B virus (HBV) (HBV/ B). METHODS: The entire nucleotide sequences of HBV/B and HBV/C were obtained from GenBank, compared and analyzed with DNAStar software. The specific primers for HBV/B (HB) and Ba (BA), Bj (BJ) were designed respectively. HB as HBV/B specific primer (sense) and HBAS-4V (designed by Japanese scientists Sugauchi et al) as a universal outer primer (antisense) were used in the first-round PCR. In the second-round PCR, HB was also used as sense primer while BA and BJ as inner primers (antisense) and they were added into a single tube for PCR reaction. The two sub-genotypes of HBV/B were identified according to the length of the PCR products. A total of 71 HBV DNA-positive serum samples were selected randomly from our laboratory, including 56 HBV/B samples identified by type-specified PCR method and 15 HBV/C samples identified by direct sequencing in preS and S Region (preS/S). All the 71 samples were detected with this semi-nested PCR method. A plasmid containing full length genomic DNA of HBV/Bj, was presented by Professor Kenji Abe as positive control of Bj. Then, the first-round PCR products of 15 HBV/B were randomly selected and sequenced directly, and their sequences were compared phylogenetically with the above known Ba and Bj sequences using Blast and DNAStar softwares to confirm the results of semi-nested PCR. RESULTS: 56 HBV/B samples were all identified as HBV/Ba by our semi-nested PCR method. 15 randomly selected PCR products were all sequenced as HBV/Ba. All of the 15 HBV/C samples were negative. CONCLUSION: A simple, rapid, sensitive and specific method for identifying sub-genotypes Ba and Bj was established with might be used for large-scale clinical and epidemiological studies.

[Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B virus infection among 12 cities in China].

OBJECTIVE: To investigate the distribution of hepatitis B virus (HBV) genotypes in patients with chronic HBV infection among 11 cities of China. METHODS: A total of 1214 serum samples from patients with chronic HBV infection were collected in 11 cities of China, including Beijing, Qingyuan, Shenzhen, Shijiazhuang, Hanchuan, Nanjing, Changchun, Liaocheng, Jinan, Ningbo and Wenzhou. Genotypes of the 1214 HBV strains were identified by PCR method with type specific primers. Parts of the results were confirmed by direct sequencing analysis of PCR products. RESULTS: Among the 1214 patients with chronic HBV infection, 0.7% (9/1214)were genotype A, 28.4% (345/1214)genotype B, 58.4% (709/1214) genotype C, and 12.4% (151/1214) genotype B and genotype C mixed infection. No other genotypes were found. Genotype C was predominant in the northern part of China, such as Changchun, Beijing, Shijiazhuang,while genotype B was more commonly seen in south of China. 71.4% (20/28) for patients from Qingyuan and 63.6% (70/110) from Shenzhen were infected with genotype B. CONCLUSION: HBV genotypes had distinct geographic distribution. Genotype B and C the predominant strains in patients with chronic HBV infection in China. Genotype C was predominantly identified in the northern part of China versus genotype B the south.

Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis.

AIM: To study effects of acetazolamide on aquaporin-1 (AQP(1)) protein expression and angiogenesis. METHODS: Establishing Lewis-lung-carcinoma model, the localization of AQP(1) in tumor tissues was investigated by immunohistochemical methods; The biological activity of acetazolamide was detected by endothelial cells proliferation test (MTT) assay and chorioallantoic membrane (CAM) vascular inhibition test. RESULTS: Immunohistochemical localization of AQP(1) in mice tumor was labeled in capillaries, post capillary venules endothelial cells. After being treated with acetazolamide, the number of capillaries and post capillary venules was significantly decreased in tumor tissue. Acetazolamide showed significant inhibitory effect on angiogenesis in CAM and endothelial cell proliferation. CONCLUSION: Acetazolamide might be identified and developed as one of potential lead compounds for a new therapeutic intervention in inhibiting cancer angiogenesis.