The Relationship between Scabies and Stroke: A Population-Based Nationwide Study.

BACKGROUND: Scabies is a commonly occurring infectious skin infestation that substantially impacts the quality of life, while stroke, which consists of a neurological deficit resulting from a lack of blood flow to the brain, carries sizable economic costs. The pathophysiologic mechanisms underlying both diseases involve inflammatory processes that are mediated by the immune system; however, no prior research has been conducted to explore the relationship between the two conditions. METHODS: This population-based nationwide study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan for a total of 6628 scabies patients, who comprised a scabies group, and a randomly selected cohort of 26,509 matching patients, who served as a control group. More specifically, the medical records for the patients in both groups were checked for seven years to identify any new cases of stroke within that seven-year follow-up period. The hazard ratio (HR) of stroke for the follow-up period was then calculated using Cox proportional hazards regressions, while comorbidities and demographic characteristics were likewise analyzed. RESULTS: During the follow-up period, 2892 patients, or 8.7%, of the overall total of 33,137 patients included in the study were newly diagnosed with a stroke. Of those newly diagnosed stroke patients, 833 were from the scabies group, and 2059 were from the control group, accounting for 12.6% and 7.8%, respectively, of the individuals in each group. With a crude hazard ratio of 1.67, the patients in the scabies group had a significantly higher risk of subsequent stroke than those in the control group, although the adjusted hazard ratio (aHR) for the scabies patients, which was determined by adjusting for covariates, was only 1.32 (95% confidence interval (CI): 1.21-1.43). CONCLUSIONS: The results of the study indicated an elevated risk of stroke among scabies patients, an association that might be contributed to by immunopathological factors. This information could serve as a reminder to clinicians to remain alert to any indications of neurological impairment in patients previously infected with scabies.

The homeobox transcription factor Irxl1 negatively regulates MyoD expression and myoblast differentiation.

Irxl1/Mkx (Iroquois homeobox-like 1/Mohawk) encodes a member of the TALE subfamily of homeodomain proteins. It is expressed in multiple mesoderm-derived tissues and has recently been shown to regulate tendon differentiation during mouse embryonic development. Previously we showed that knockdown of Irxl1 in zebrafish caused a deficit in neural crest cells which consequently resulted in deformation of craniofacial muscles and arch cartilages. Here, we further demonstrate that loss of Irxl1 function results in deformed somites with disordered muscle fibers and myotendinous junctions. Because expression of myoD is increased in the somites of Irxl1 knockdown morphants, we test whether Irxl1 negatively regulates myoD expression. When stable C2C12 myoblasts overexpressing Irxl1/Mkx were induced to differentiate, myotube formation was inhibited and protein levels of myoD and myosin heavy chain were decreased accordingly. A series of deletion constructs of myoD promoter fragments were tested by luciferase reporter assays, which identified a promoter fragment that is necessary and sufficient for Irxl1-mediated repression. Direct interaction of Irxl1 and myoD promoter was subsequently elucidated by yeast one-hybrid assays, electrophoretic mobility shift assays and chromatin immunoprecipitation analysis. Furthermore, mouse Mkx also binds to and represses myoD promoter. These results indicate that Irxl1/Mkx can repress myoD expression through direct binding to its promoter and may thus play a negative regulatory role in muscle differentiation.

The critical role of protein arginine methyltransferase prmt8 in zebrafish embryonic and neural development is non-redundant with its paralogue prmt1.

Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of PRMT1 with an extra N-terminal sequence and brain-specific expression. We use zebrafish (Danio rerio) as a vertebrate model to study PRMT8 function and putative redundancy with PRMT1. The transcripts of zebrafish prmt8 were specifically expressed in adult zebrafish brain and ubiquitously expressed from zygotic to early segmentation stage before the neuronal development. Whole-mount in situ hybridization revealed ubiquitous prmt8 expression pattern during early embryonic stages, similar to that of prmt1. Knockdown of prmt8 with antisense morpholino oligonucleotide phenocopied prmt1-knockdown, with convergence/extension defects at gastrulation. Other abnormalities observed later include short body axis, curled tails, small and malformed brain and eyes. Catalytically inactive prmt8 failed to complement the morphants, indicating the importance of methyltransferase activity. Full-length prmt8 but not prmt1 cRNA can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with the N-terminus of Prmt8 can rescue the prmt8 morphants. In contrast, N-terminus- deleted but not full-length prmt8 cRNA can rescue the prmt1 morphants as efficiently as prmt1 cRNA. Abnormal brain morphologies illustrated with brain markers and loss of fluorescent neurons in a transgenic fish upon prmt8 knockdown confirm the critical roles of prmt8 in neural development. In summery, our study is the first report showing the expression and function of prmt8 in early zebrafish embryogenesis. Our results indicate that prmt8 may play important roles non-overlapping with prmt1 in embryonic and neural development depending on its specific N-terminus.

Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones.

BACKGROUND/OBJECTIVES: Our aim was to investigate the calcium content of different gallstone compositions and the pathogenic mechanisms of calcium carbonate gallstones. METHODS: Between August 2001 and July 2007, gallstones from 481 patients, including 68 calcium carbonate gallstones, were analyzed for total calcium content. Gallbladder bile samples from 33 cases and six controls were analyzed for pH, carbonate anion level, free-ionized calcium concentration and saturation index for calcium carbonate. RESULTS: Total calcium content averaged 75.6 %, 11.8 %, and 4.2 % for calcium carbonate, calcium bilirubinate and cholesterol gallstones. In 29.4 % of patients, chronic and/or intermittent cystic duct obstructions were caused by polypoid lesions in the neck region and 70.6 % were caused by stones. A total of 82 % of patients had chronic low-grade inflammation of the gallbladder wall and 18.0 % had acute inflammatory exacerbations. In the bile, we found the mean pH, mean carbonate anion, free-ionized calcium concentrations, and mean saturation index for calcium carbonate to be elevated in comparison to controls. CONCLUSION: From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO(3) from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate.

Long tract of untranslated CAG repeats is deleterious in transgenic mice.

The most frequent trinucleotide repeat found in human disorders is the CAG sequence. Expansion of CAG repeats is mostly found in coding regions and is thought to cause diseases through a protein mechanism. Recently, expanded CAG repeats were shown to induce toxicity at the RNA level in Drosophila and C. elegans. These findings raise the possibility that CAG repeats may trigger RNA-mediated pathogenesis in mammals. Here, we demonstrate that transgenic mice expressing EGFP transcripts with long CAG repeats in the 3' untranslated region develop pathogenic features. Expression of the transgene was directed to the muscle in order to compare the resulting phenotype to that caused by the CUG expansion, as occurs in myotonic dystrophy. Transgenic mice expressing 200, but not those expressing 0 or 23 CAG repeats, showed alterations in muscle morphology, histochemistry and electrophysiology, as well as abnormal behavioral phenotypes. Expression of the expanded CAG repeats in testes resulted in reduced fertility due to defective sperm motility. The production of EGFP protein was significantly reduced by the 200 CAG repeats, and no polyglutamine-containing product was detected, which argues against a protein mechanism. Moreover, nuclear RNA foci were detected for the long CAG repeats. These data support the notion that expanded CAG repeat RNA can cause deleterious effects in mammals. They also suggest the possible involvement of an RNA mechanism in human diseases with long CAG repeats.

The predominant protein arginine methyltransferase PRMT1 is critical for zebrafish convergence and extension during gastrulation.

Protein arginine methyltransferase (PRMT)1 is the predominant type I methyltransferase in mammals. In the present study, we used zebrafish (Danio rerio) as the model system to elucidate PRMT1 expression and function during embryogenesis. Zebrafish prmt1 transcripts were detected from the zygote period to the early larva stage. Knockdown of prmt1 by antisense morpholino oligo (AMO) resulted in delayed growth, shortened body-length, curled tails and cardiac edema. PRMT1 protein level, type I protein arginine methyltransferase activity, specific asymmetric protein arginine methylation and histone H4 R3 methylation all decreased in the AMO-injected morphants. The morphants showed defective convergence and extension and the abnormalities were more severe at the posterior than the anterior parts. Cell migration defects suggested by the phenotypes were not only observed in the morphant embryos, but also in a cellular prmt1 small-interfering RNA knockdown model. Rescue of the phenotypes by co-injection of wild-type but not catalytic defective prmt1 mRNA confirmed the specificity of the AMO and the requirement of methyltransferase activity in early development. The results obtained in the present study demonstrate a direct link of early development with protein arginine methylation catalyzed by PRMT1.

Muscleblind participates in RNA toxicity of expanded CAG and CUG repeats in Caenorhabditis elegans.

We have utilized Caenorhabditis elegans as a model to investigate the toxicity and underlying mechanism of untranslated CAG repeats in comparison to CUG repeats. Our results indicate that CAG repeats can be toxic at the RNA level in a length-dependent manner, similar to that of CUG repeats. Both CAG and CUG repeats of toxic length form nuclear foci and co-localize with C. elegans muscleblind (CeMBL), implying that CeMBL may play a role in repeat RNA toxicity. Consistently, the phenotypes of worms expressing toxic CAG and CUG repeats, including shortened life span and reduced motility rate, were partially reversed by CeMbl over-expression. These results provide the first experimental evidence to show that the RNA toxicity induced by expanded CAG and CUG repeats can be mediated, at least in part, through the functional alteration of muscleblind in worms.

Overcoming the difficulties in laparoscopic management of contracted gallbladders with gallstones: possible role of fundus-down approach.

BACKGROUND: The aim of this study is to compare efficacy and complications between fundus-down and conventional laparoscopic cholecystectomy (LC) in treating contracted gallbladders with gallstones. METHODS: Between January 1999 and May 2008, 64 patients with contracted gallbladders and gallstones were included in the study. Main outcome measures included conversion rate, complication rate, bile duct injury rate, operation time, and postoperative stay. RESULTS: The average postoperative hospital stay for fundus-down technique was 5 ± 3 days, and 7 ± 3 days for conventional technique (P = 0.003). The conversion rate and complication rate were 0% (0/33) and 3.00% (1/33) for fundus-down technique, and 32.3% (10/31) and 22.6% (7/31) for conventional technique (P = 0.0009 and 0.02, respectively). In subgroup analysis, fundus-down LC seemed to lower the bile duct injury rate from 2/31 (6.5%) to 0/33 (0%) compared with 6/1,468 (0.4%) (P = 0.01 between 6.5% and 0.4% vs. P = 1.00 between 0% and 0.4%). CONCLUSIONS: It appears that fundus-down laparoscopic cholecystectomy is associated with lower conversion and complication rates and shorter postoperative hospital stay as compared with conventional laparoscopic cholecystectomy when used to treat patients with contracted gallbladders and gallstones.

Pathophysiological significance of gallbladder volume changes in gallstone diseases.

AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients. METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student's t tests were used. P < 0.05 was deemed statistically significant. RESULTS: The fasting GBV was larger in late stage than in early/second stage acute cholecystitis gallbladders (84.66 +/- 26.32 cm(3), n = 12, vs 53.19 +/- 33.80 cm(3), n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 +/- 15.00 cm(3) vs 6.77 +/- 15.75 cm(3), P < 0.0001)/(34.6% +/- 10.6%, n = 65, vs 53.3% +/- 24.9%, n = 53, P < 0.0001). CONCLUSION: GBV increases as acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones.

Laparoscopic primary closure of common bile duct combined with percutaneous cholangiographic drainage for treating choledocholithiasis.

The aim of this study was to compare the efficacy and safety of laparoscopic primary closure of the common bile duct (CBD) combined with percutaneous transhepatic cholangiographic drainage (PTCD) and laparoscopic choledocholithotomy with T-tube placement for the treatment of CBD stones. Between January 1991 and July 2002, 50 patients with choledocholithiasis and a CBD diameter larger than or equal to 1 cm underwent laparoscopic CBD explorations. The study group consisted of 10 patients undergoing laparoscopic primary closure of the CBD combined with PTCD. The control group consisted of 40 patients undergoing laparoscopic choledocholithotomy with T-tube placement. Parameters were compared statistically. The study group showed higher female/male ratio (6/4 vs. 8/32, P = 0.02), less stone numbers (1.90 +/- 0.88 vs. 3.40 +/- 1.65, P = 0.0078), shorter operation time (138 +/- 37 minutes vs. 191 +/- 75 minutes, P = 0.014), and shorter postoperative stays (7 +/- 3 days vs. 10 +/- 3 days, P = 0.0013). It seems that laparoscopic primary closure of the CBD combined with PTCD can shorten the operation time and postoperative stays as compared with laparoscopic choledocholithotomy with T-tube placement for the treatment of CBD stones.

The zebrafish homeobox gene irxl1 is required for brain and pharyngeal arch morphogenesis.

Iroquois homeobox-like 1 (irxl1) is a novel member of the TALE superfamily of homeobox genes that is most closely related to the Iroquois class. We have identified the zebrafish irxl1 gene and characterized its structure. The protein contains a homeodomain that shares 100% sequence identity with other vertebrate orthologs. During embryogenesis, irxl1 is expressed from 18 hours postfertilization onward and prominent expression is detected in the pharyngeal arches. Knockdown of irxl1 by morpholinos results in malformed brain and arch structures, which can be partially rescued by cRNA injection. The heads of the morphants become small and flat, and extensions along the anterior-posterior/dorso-ventral axes are reduced without affecting regional specification. Loss of irxl1 function also causes deficit in neural crest cells which consequently results in partial loss of craniofacial muscles and severe deformation of arch cartilages. These observations suggest that irxl1 may regulate factors involved in brain and pharyngeal arch development.

Zebrafish muscleblind-like genes: identification, structural features and expression.

Muscleblind-like (MBNL) proteins are a family of RNA-binding proteins that participate in the regulation of tissue-specific alternative splicing. Misregulation of MBNL activity in humans leads to pathogenesis. Here, we report upon the identification and characterization of three muscleblind-like genes in zebrafish (zmbnl1, zmbnl2 and zmbnl3). Alternative splicing of the three zmbnl primary transcripts gives rise to at least four protein isoforms for zmbnl1, four for zmbnl2 and five for zmbnl3, respectively. All of the zmbnl proteins contain the characteristic CCCH zinc fingers required for RNA binding. In addition, several structural motifs, including a C-terminal Ser/Thr-rich region, are conserved among Mbnl orthologs in vertebrates, but not invertebrates. These genes are broadly expressed in most adult tissues. However, the relative expression levels of specific spliceforms vary across different tissues. During embryogenesis, zmbnl1 and zmbnl2 are both maternally and zygotically expressed. In contrast, zmbnl3 transcripts are not detected until the late pharyngula stage. Our results reveal the expression pattern of various mbnl spliceforms for the first time and suggest that they may play specific roles during fish development.

Growth-dependent effect of muscleblind knockdown on Caenorhabditis elegans.

The muscleblind-like (MBNL) proteins are tissue-specific alternative splicing regulators. Dysfunction of MBNL has been implicated in the pathogenesis of expanded CUG repeats-associated myotonic dystrophy (DM). In this study, we describe the identification and functional characterization of a Caenorhabditis elegans muscleblind (CeMbl) gene. CeMbl is a single gene alternatively spliced to generate two isoforms (CeMBL-A and CeMBL-B). It displays a high homology with human MBNL1 in the C3H1 zinc finger domains. CeMbl transcripts are detected in larval and adult stages. However, inactivation of CeMbl by RNA-mediated interference results in muscle phenotype only at adulthood. Immunofluorescence staining using anti-vinculin antibody reveals that the organization of dense body is disrupted in affected worms. Our results demonstrate a growth-dependent requirement of CeMbl on muscle structure and function. They also provide a possible molecular basis for the developmentally regulated toxicity of expanded CUG repeats.

Functional studies of the effect of NO donor on human CLCN1 polymorphism/mutants expressed in Xenopus laevis oocytes.

In this study, we investigated the effect of NO donor, diethylamine/nitric oxide (DEA/NO), on the electrophysiological behavior of human skeletal muscle chloride channel (CLCN1). The wild-type and variants of CLCN1, including one polymorphism (P727L) and four mutants (T631I, D644G, G482R, and S471F), were expressed in Xenopus oocytes and the ionic current was measured by two-electrode voltage-clamp method. Our results revealed that there is no significant difference in the current-voltage relationships and half-voltage values of open probability between wild-type and variants of CLCN1 except for G482R. Application of the DEA-NO (0.1mM) significantly increases the channel conductance of wild-type, T631I, D644G, and S471F, but not P727L. This indicates that P727L polymorphism causes loss of sensitivity of CLCN1 to the DEA/NO treatment, which could be due to a conformational change caused by proline substitution. The data suggest that the polymorphic changes may affect the function of CLCN1 in response to the treatment of chemical compounds.

Length-dependent toxicity of untranslated CUG repeats on Caenorhabditis elegans.

Expansion of CTG repeat within the 3'-untranslated region of the DMPK gene causes the most common neuromuscular disorder, myotonic dystrophy type 1 (DM1), through a RNA trans-dominant mechanism. Here, we explore Caenorhabditis elegans as a model system to investigate the repeat size-dependent toxic effect by expression of green fluorescent protein (GFP) transcripts with various lengths of untranslatable CUG repeats (CUG5, CUG30, CUG83, CUG125, and CUG213) in body wall muscles. CUG213 animals died during embryogenesis or showed retarded growth at larval stages due to defective muscle development. CUG125 animals, although can produce offspring, exhibited uncoordinated muscle function, deviated electropharyngeogram, and an age-dependent abnormality in muscle structure. Most CUG83 animals had normal muscle structure and function as those expressing 30 and shorter repeats. Our results demonstrate for the first time that the in vivo toxicity of CUG repeats is repeat length- and growth-regulated and suggest that expanded CUG repeats are sufficient to cause congenital-like phenotypes in living organisms.

Functional characterization of CLCN1 mutations in Taiwanese patients with myotonia congenita via heterologous expression.

Mutations in the CLCN1 gene frequently associate with myotonia congenita (MC). We have recently reported several CLCN1 mutants in Taiwanese patients. To further elucidate the correlation between the genotypes and phenotypes, in this study, we used Xenopus oocyte as a system to investigate the functional effects of these mutants. The fs793X and G482R mutants, which were suggested to have a dual inheritance pattern, were found to cause a functional loss of CLCN1 channels. While co-expression of fs793X and wild-type (WT) showed a reduction of chloride conductance by about half of WT channels, the activation curve of voltage-dependence was not shifted. A compound heterozygous mutant, P575S/D644G, was found in a patient. When both mutants were co-expressed in oocytes, they caused a shift of the voltage-dependence of activation curve to more positive values than individual mutant. This indicates that both P575S and D644G mutants may contribute cooperatively to change the gating property of CLCN1 channel. Interestingly, the S471F mutant did not cause significant alternation of functional properties. Consistent with the fact that T631I mutant was found in three asymptomatic individuals, the electrophysiological parameters of T631I were similar to those of WT CLCN1 channels, suggesting that T631I is a neutral mutation. These results further clarify the correlation between the mutations and their functional implications of CLCN1 channels.

Novel CLCN1 mutations in Taiwanese patients with myotonia congenita.

We have performed genetic screening on the skeletal muscle chloride channel gene (CLCN1) in Taiwanese population. A total of four patients with myotonia congenita (MC) together with 106 normal individuals were examined. All 23 exons of the CLCN1 gene were analysed by direct sequencing of PCR products to detect the nucleotide changes. Five mutations and three polymorphisms were identified in this study. Among these, three missense mutations (S471F, P575S, D644G) and one polymorphism (T736I) are novel and could be unique to the Taiwanese. In addition, a previously documented recessive G482R mutation was identified in a heterozygous patient and his nonsymptomatic father, indicating that this mutation might indeed function recessively or dominantly with incomplete penetrance. In conclusion, this is the first report of MC in Taiwan with proven CLCN1 gene mutations and showing high molecular heterogeneity in Taiwanese MC patients.

Cloning and developmental expression of p73 cDNA in zebrafish.

p73 is one of the p53 family members which are transcription factors involved in the regulation of cell proliferation, apoptosis, and differentiation. In this study, we cloned the p73 cDNA from zebrafish ovary RNA. The consensus open reading frame (1923bp) encodes a polypeptide of 640 amino acids which shares 70-95% identity to the p73 of other vertebrates. Expression of zebrafish p73 mRNA is restricted to tissues such as skin, fin, brain, ovary, and testis, in contrast to the ubiquitous expression of zebrafish p53 and p63. During embryonic development, p73 transcripts are detected from the zygote period to the early larva stage. Whole-mount in situ hybridization reveals that p73 expression is in the brain, including olfactory bulbs, telencephalon, and hypothalamus, as well as in the pharyngeal arches and the nose. Moreover, p73 protein is found in the ovary and testis sections by immunohistochemical staining.

Increased (CTG/CAG)(n) lengths in myotonic dystrophy type 1 and Machado-Joseph disease genes in idiopathic azoospermia patients.

BACKGROUND: An increase in CAG trinucleotide repeat length in the androgen receptor (AR) gene has been linked to idiopathic azoospermia. METHODS: In order to test whether other (CAG/CTG)(n) loci are also affected, the (CAG/CTG)(n) frequency distribution at myotonic dystrophy type 1 (DM1), Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 8 (SCA8) loci, in addition to the AR gene, was investigated in 48 azoospermia patients and 47 controls. RESULTS: The median CAG repeat length in the AR gene was significantly longer in azoospermia patients than in controls (23 versus 21, P < 0.001). Significant differences were also noted in the upper tails of trinucleotide repeat length distributions at both DM1 and MJD loci between the two populations. At the DM1 locus, alleles of more than 18 repeats were observed only in azoospermia patients, and not in controls (P = 0.014). At the MJD locus, the frequency of normal alleles (ANs) with 29 or more CAG repeats was also much higher in azoospermia patients (29.2 versus 7.4%; P = 0.0001). However, the repeat length distribution at DRPLA and SCA8 loci did not differ in the two groups. CONCLUSIONS: These data indicated that, at least in a subset of azoospermia patients, there was an increase in the number of trinucleotide repeats in some disease loci. Thus, it is noteworthy to evaluate whether offspring of these azoospermia patients, if born by assisted reproductive technologies, have an increased risk of trinucleotide repeat diseases.

Overexpression but lack of mutation and methylation of p73 in hepatocellular carcinoma.

p73 is one of the family proteins that share structural and functional homologies with the tumor suppressor p53. To analyze the status of p73 in hepatocellular carcinoma (HCC), the allelic loss, allelic expression, mutation and methylation status of the p73 gene were examined in 18 paired HCC and normal tissues. No allelic loss was found. All heterozygous individuals contained RNA of both alleles, indicating that p73 was biallelically expressed in the liver. Notably, semiquantitative reverse transcriptase polymerase chain reaction analysis showed that p73 was consistently overexpressed in the cancerous tissues. Single-stranded conformation polymorphism and sequencing analysis revealed several polymorphisms, but no mutations were found in the entire coding sequence. Finally, the methylation patterns in the promoter and exon 1 regions of p73 were not altered in the cancerous tissues. These results do not support p73 as a tumor suppressor in HCC, but suggest that overexpression of p73 may in some way be associated with the pathogenesis of HCC.