Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Dronedarone and Amiodarone Induce Dyslipidemia and Thyroid Dysfunction in Rats.

BACKGROUND/AIMS: Amiodarone, a thyroid hormone-like molecule, can induce dyslipidemia and thyroid dysfunction. However, the effects of dronedarone on lipid metabolism and of both dronedarone and amiodarone on thyroid function and lipid metabolism remain unknown. METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups (10 in each group): normal control (NC), amiodarone-treated (AMT), dronedarone-treated (DRT), rats treated with amiodarone combined with polyene phosphatidylcholine (AC), and rats treated with dronedarone combined with polyene phosphatidylcholine (DC). Rats were given amiodarone (120 mg/kg/d), dronedarone (120 mg/kg/d), and polyene phosphatidylcholine (200 mg/kg/d) for 13 weeks. At the end of weeks 4, 8, 12, and 13, plasma-free triiodothyronine (FT3), free thyroxine (FT4), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were determined. At the end of this protocol, rats were sacrificed and the thyroid glands were isolated, weighed, and examined histopathologically. The protein expression of Bcl-2 was measured by immunochemical staining. The mRNA expression of thyroglobulin (Tg), type-1 deiodinase (D1), and thyroid peroxidase (TPO) were detected by polymerase chain reaction (PCR). RESULTS: Compared with the NC group, FT3 and FT4 levels in the DRT and DC groups significantly increased at week 4 but declined thereafter. The AMT and AC groups had lower FT3 levels but comparable FT4 levels. The levels of TG, LDL-c, and HDL-c in the NC group were lower than those in the other groups whereas the LDL-c/HDL-c ratio was lowest in the AMT group. Bcl-2 expression significantly increased in the DRT group. The mRNA expression of Tg increased whereas the mRNA expression of D1 decreased. Dronedarone induced hyperthyroidism at the early stage and hypothyroidism at the late stage whereas amiodarone only caused hypothyroidism. CONCLUSION: Both dronedarone and amiodarone can induce dyslipidemia and increase the levels of TC, LDL-c, and HDL-c, and these effects may be associated with thyroid dysfunction.

Population genomics reveals that a missense mutation in EDNRB2 contributes to white plumage color in pigeons.

Plumage color is an important economic trait for breed feature identification and consumer's requirements in pigeons. The domestic pigeon has multiple types of plumage color, thereby providing a unique opportunity to identify the genetic basis of plumage coloration. White feather color is common for meat and medicinal use. To investigate the genetic variation associated with white plumage color in pigeons, we use genome resequencing and population genomics to identify the genomic regions with strong selective signature between pigeons with brown and white plumage color. Meanwhile, we obtained some candidate genes with melanin or melanosome biosynthesis in selected regions. Finally, we identified a missense mutation p.E256K in the EDNRB2 completely associated with white plumage color. These findings provide a basis for genetic variation in pigeons with plumage color phenotype.

High endothelial venules proportion in tertiary lymphoid structure is a prognostic marker and correlated with anti-tumor immune microenvironment in colorectal cancer.

BACKGROUND: High endothelial venules (HEV) and tertiary lymphoid structures (TLS) are associated with clinical outcomes of patients with colorectal cancer (CRC). However, because HEV are components of TLS, there have been few studies of the role of the HEV proportion in TLS (HEV/TLS). This study investigated the role of the HEV/TLS and its relationship with the tumor immune microenvironment in CRC. METHODS: A retrospective analysis of 203 cases of tissue pathologically diagnosed as CRC after general surgery was performed at the First Affiliated Hospital of Jinan University from January 2014 to July 2017. Paraffin sections were obtained from the paracancerous intestinal mucosal tissues. The area of HEV and TLS and immune cells were detected by immunohistochemistry. We further divided the positive HEV expression group into the high HEV/TLS group and the low HEV/TLS group by the average area of HEV/TLS. After grouping, the data were also analyzed using the chi-square test, Kaplan-Meier method, and univariate and multivariate Cox proportional risk regression analyses. A correlation analysis of the HEV/TLS and immune cells as well as angiogenesis was performed. RESULTS: Patients with a high HEV/TLS in CRC tissue were associated with longer OS, DFS and lower TNM stage. Meanwhile, CRC tissue with a high HEV/TLS showed a greater ability to recruit the CD3+ T cells, CD8+ T cells and M1 macrophages and correlated with less angiogenesis. Conclusively, high HEV/TLS links to the favorable prognosis of CRC patients and correlated with anti-tumor immune microenvironment, which can be a potential biomarker for prognosis of CRC patients. CONCLUSION: A high HEV/TLS is associated with a favorable prognosis for CRC and is correlated with the anti-tumor immune microenvironment. Therefore, it is a potential biomarker of the CRC prognosis.KEY MESSAGESHigh HEV/TLS is associated with a favorable prognosis for CRC.High HEV/TLS correlated with the anti-tumor immune microenvironment of CRC and can serve as a novel prognostic biomarker.

Effectiveness of Trimetazidine in Patients with Chronic Heart Failure Stratified by the Expression of Soluble Suppression of Tumorigenicity-2 (sST2): A Prospective Cohort Study.

INTRODUCTION: Trimetazidine has been reported to have potential benefits in patients with chronic heart failure (CHF). Soluble suppression of tumorigenicity-2 (sST2) was shown to worsen CHF and, hence, has a diagnostic value in heart failure. The aim of the present study was to evaluate the effectiveness of trimetazidine in patients expressing high and low levels of sST2 compared with their matched placebo. METHODS: In this prospective cohort study, 170 patients were enrolled. Patients expressing more than 35 ng/mL sST2 (S+) were split into a trimetazidine group (group A) and placebo group (group B). Likewise, patients expressing 35 ng/mL or less of sST2 (S-) were divided into a trimetazidine (group C) and placebo group (group D). Patients in both the trimetazidine groups were administered 20-mg twice-a-day doses of trimetazidine. Trimetazidine effectiveness was determined in terms of changes in cardiac function, motor function, and mental status at 1, 3, 6, and 12 months from baseline among the four groups. RESULTS: A total of 158 patients were included for final data analysis (group A, n = 50; group B, n = 57; group C, n = 27; group D, n = 24). On comparing different outcomes between the four groups and across the time points, significant difference was observed between the groups in ejection fraction (EF; P < 0.001), cardiac index (CI; P < 0.001), New York Heart Association score (P < 0.001), 6-min walk test (P < 0.001), Veterans Specific Activity Questionnaire (VSAQ; P < 0.001), Minnesota Living with Heart Failure Questionnaire (MLHFQ; P < 0.001), hospital anxiety and depression scores (P < 0.001), and Copenhagen Burnout Inventory (P < 0.001). Significant difference in systolic blood pressure (P < 0.001), heart rate (P < 0.001), EF (P < 0.001), CI (P < 0.001), VSAQ (P = 0.017), and MLHFQ (P < 0.001) was observed. CONCLUSION: Trimetazidine demonstrated an overall improvement in cardiac function, motor function, quality of life (QoL), and mental status in both S+ and S- patients. Among patients administered trimetazidine, significant changes in maximum outcomes were observed among those expressing higher levels of sST2 compared with placebo.

Regulation of acyl-coenzyme A: cholesterol acyltransferase 2 expression by saturated fatty acids.

OBJECTIVE: To verify the regulation of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT 2), which is associated with cholesterol metabolism, by saturated fatty acids (SFAs). METHODS: Palmitic acid (PA), the most abundant saturated fatty acid in plasma, and oleic acid (OA), a widely distributed unsaturated fatty acid, were used to treat hepatic cells HepG2, HuH7, and mouse primary hepatocytes. In addition, PA at different concentrations and PA treatment at different durations were applied in HepG2 cells. In in vivo experiment, three-month male C57/BL6 mice were fed with control diet and SFA diet containing hydrogenated coconut oil rich of SFAs. The mRNA level of ACAT2 in those hepatic cells and the mouse livers was detected with real-time polymerase chain reaction (PCR). RESULTS: In the three types of hepatic cells treated with PA, that SFA induced significant increase of ACAT2 expression (Pü0.01), whereas treatment with OA showed no significant effect. That effect of PA was noticed gradually rising along with the increase of PA concentration and the extension of PA treatment duration (both Pü0.05). SFA diet feeding in mice resulted in a short-term and transient increase of ACAT2 expression in vivo, with a peak level appearing in the mice fed with SFA diet for two days (Pü0.05). CONCLUSION: SFA may regulate ACAT2 expression in human and mouse hepatic cells and in mouse livers.

Applied anatomy of the lower cervical pedicle screw insertion.

OBJECTIVE: To ascertain an accurate approach to inserting the pedicle screw into C3-C7 segments of the cervical vertebra. METHODS: Anatomic morphology of lateral mass and pedicle, and their anatomic relationship with the adjacent tissue were observed on C3-C7 segments of 25 adult embalmed cadavers (50 sides). RESULTS: 1) The inferior edge of the base of the posterior tubercle of the transverse process and the inferior edge of the pedicle were connected with each other on 25 adult embalmed cadavers (50 sides). The transverse section which passed through the median point between the superior edge and the inferior edge of the base of the posterior tubercle of the transverse process, and the transverse section which passed through the central axis between the superior edge and the inferior edge of the pedicle, were in the same horizontal plane. The superior and inferior position of placing the pedicle screw was determined by this transverse section, which passed through the median point between the superior and the inferior edge of the base of the posterior tubercle of the transverse process. 2) There was a directed internal-downwards "triangular sulcule" between the base of the posterior tubercle of the transverse process and the anterolateral edge of the inferior articular process. The anterior wall of the triangular sulcule was the base of the posterior tubercle of the transverse process, the posterior wall was the anterolateral edge of the inferior articular process, and the bottom of the sulcule was connected with the interior edge of the pedicle. The vertical length between the top of triangle and the planes of inferior edge of the pedicle was (2.78+/-1.71) mm. The inferior edge of the cervical pedicle could be detected using a blunt probe along the "triangular sulcule" between the base of the posterior tubercle of the transverse process and the anterolateral edge of the inferior articular process in surgical operation. 3) The lateral fovea of the articular process was observed on all lateral masses (50 sides). The internal and external position of the entrance point could depend on anatomic landmarks: the lateral edge of the lateral fovea of the articular process. The horizontal length between the lateral fovea of the articular process and the entrance point was (3.14+/-1.45) mm. 4) The diameter of pedicle screw, about (2.78+/-1.71) mm, was the transverse diameter of the cancellous bone of the greatest narrow part of the cervical pedicle. CONCLUSIONS: The median point between the superior edge and the inferior edge of the base of the posterior tubercle of the transverse process, the lateral fovea of the articular process, and the triangular sulcule between the base of the posterior tubercle of the transverse process and the anterolateral edge of inferior articular process, are easy to be exposed and identified in surgical operation. The pedicle screw can be precisely inserted through this method.

Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells.

OBJECTIVE: Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of microRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. METHODS: Here we first used a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. RESULTS: We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the viability and proliferation of HCC cells, and promot the migration and invasion of HCC cells. CONCLUSIONS: miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC.

Changes of Plasma Tumor Necrosis Factor α and C-Reactive Protein Levels in Patients with Hypertension Accompanied by Impaired Glucose Tolerance and their Clinical Significance.

BACKGROUND: Chronic inflammation could affect the occurrence and development of malignant tumors. To explore the levels of tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) in patients accompanied by impaired glucose tolerance (IGT) and their clinical significance. MATERIALS AND METHODS: A total of 210 patients hospitalized in Affiliated Hospital of Taishan Medical University from Jun., 2013 to Dec., 2014 were selected, in which 92 cases were accompanied by IGT. Meanwhile, 80 randomly-selected healthy people by physical examination were as the control. The levels of routine biochemical indexes, plasma TNF-α and CRP in all subjects were measured. RESULTS: Both systolic and diastolic pressures in hypertension group and hypertension plus IGT group were significantly higher than in control group (p<0.01), but there was no statistical significance between these two groups (p>0.05). The levels of fasting plasma glucose (FPG) and blood glucose 2 h after taking glucose in hypertension plus IGT group were markedly higher than other groups (p<0.01). Homeostasis model assessment-insulin resistance (HOMA-IR), TNF-α and CRP contents were on the progressive increase in control, hypertension and hypertension plus IGT groups, but significant differences were presented among each group (P<0.01). Hypertension accompanied by IGT had a significantly-positive association with CRP, TNF-α, FPG and blood glucose 2h after taking glucose. CONCLUSIONS: The levels of plasma TNF-α and CPR in patients with hypertension accompanied by IGT increase significantly, indicating that inflammatory reaction in these patient increases, thus suggesting that these patients should be focused regarding cancer prevention.

Inhibition mechanism of a newly cloned candidate tumor suppressor gene JST during hepatocarcinogenesis and its abnormal expression in human hepatocellular carcinoma from Qidong liver cancer risk area, China.

BACKGROUND/AIMS: To study inhibition effect of a newly cloned candidate tumor suppressor gene (JST) during hepatocarcinogenesis and its normal expression in human hepatocellular carcinoma from Qidong liver cancer risk area, China. METHODOLOGY: By preparing rabbit anti-human JST polyclonal antibody, constructing of JST frameshift mutant and exploring RT-PCR, in situ hybridization, immunohistochemistry, Western blot, Northern blot, cDNA expression microarray, co-immunoprecipitation and the tumorigenicity assay in vivo and in vitro, gene treatment, etc, JST gene expression and inhibition tumor growth effects were analyzed, including 150 pairs of HCC specimens and their adjacent para-cancerous tissues, 8 cases of normal liver tissues and QGY7701, HepG2, Hep3B cell line. Its relationship with the invasiveness of HCC from Qidong was also investigated. RESULTS: Our results showed that there is expression difference for JST between liver cancer and para-cancerous tissue and the results of RT-PCR, in situ hybridization, immunohistochemistry, Western blot, Northern blot suggested that it is a down-regulation gene. The labeling index (LI) of cancer tissue and para-cancerous tissue was (70.2+/-8.7) and (9.4+/-2.8) respectively (p<0.01), lower LI was closely related with invasiveness of HCC, decreased expression of JST was also shown by Western blotting. Results of RT-PCR showed the JST gene expression index (EI) of HCCs was lower than that of para-cancerous tissue and normal liver tissue and there are some sequence differences between cancer and para-cancerous tissues. Northern blot showed JST having down-regulation expression among 92.20% (138/150) of patients. Using in situ hybridization, the signal corresponding to JST mRNA was particularly weak in cytoplasm of HCC when compared with those of para-cancerous and normal liver tissues. Less expression of JST was also found to be correlated with high metastasis potentiality of HCC. JST overexpression inhibits DNA synthesis and apoptosis in QGY7701 cells. QGY7701 cell transfected with JST is more inhibited in soft agar than that of vector transfected control cells (p<0.01) or QGY7701 cells stably transfected with the JST frameshift mutant. The tumor formation is more inhibited in the QGY7701-pcDNA3.1-JST group than that in the QGY7701-pcDNA3.1, QGY7701-pcDNA3.1-JST frameshift mutant group. cDNA expression microarray showed expression differences of 10% (20/200,18 up-regulation; 2 up-regulation) tumor genes were considered significant between QGY7701-pcDNA3.1-JST and QGY7701-pcDNA3.1. Using a co-immunoprecipitation approach, intracellular binding of JST and p53 was found. Higher levels of p53 were detected following infection with pcDNA3.1-JST when compared with pcDNA3.1. Induction of FasL could be demonstrated in Hep3B and in HepG2 cells following transfection pcDNA3.1-JST, but not following transfection pcDNA3.1. CONCLUSIONS: JST is a putative tumor suppressor gene. Overexpression of JST gene may contribute to inhibiting the occurrence, advancement and invasiveness of HCC from Qidong, a high risk area in China.

Predictive value of left ventricular remodeling by area strain based on three-dimensional wall-motion tracking after PCI in patients with recent NSTEMI.

We aimed to explore whether a novel left ventricular performance index, area strain (AS), based on three-dimensional wall-motion tracking (3-D-WMT) done before and after percutaneous coronary intervention (PCI) could predict left ventricular (LV) remodeling in patients with recent non-ST elevation myocardial infarction (NSTEMI). Sixty-one patients (53.6 ± 8.8 years) with recent NSTEMI were enrolled. Coronary angiography and PCI were undertaken for reperfusion. Parameters of myocardial deformation (including LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, LV global and regional peak area strain) were measured by 3-D-WMT before and 1 week after reperfusion therapy. Six months after reperfusion, LV negative remodeling was defined as lack of improvement in LV function, with increase in LV end-diastolic volume ≥15%. Patients were subdivided into remodeled group (n = 25) and non-remodeled group (n = 36) at follow-up. Patients with negative LV remodeling had significantly higher cardiac troponin I (cTnI) levels at baseline (21.21 ± 12.22 vs. 15.56 ± 8.91 ng/mL; p = 0.0357), higher B-type natriuretic peptide (BNP) level (247.56 ± 177.39 vs. 170.53 ± 97.89 pg/mL; p = 0.0336) and reduced global AS (-27.9 ± 4.6% vs. -31.9 ± 4.3%; p = 0.001) than those without remodeling. Global AS at baseline had a significantly close correlation with cTnI level 36 h after MI (r = 0.71, p < 0.001). Moreover, a weak relationship was found between LV global AS at baseline and BNP level 24 h after myocardial infarction (r = 0.423, p < 0.001). By multivariate logistic regression analysis, lack of improvement of global AS 1 week after PCI was found to be a powerful independent predictor of negative LV remodeling at follow-up (OR = 1.41, 95% CI 1.28-3.27, p = 0.003). In particular, a global AS ≤32% (absolute value) showed a sensitivity and a specificity of 86.1% and 68.0% in predicting negative LV remodeling. These data suggest that AS could be used to assess myocardial global and regional LV function with good feasibility and repeatability. Global AS 1 week after PCI is a good independent predictor of negative LV remodeling after 6-month follow-up.

Regulation of nitric oxide generation by up-regulated arginase I in rat spinal cord injury.

Recently, arginase is suggested to regulate nitric oxide production by competing with nitric oxide synthase for the same substrate, L-arginine, in experimental asthma. We investigated the role of arginase and its relationship to nitric oxide production after spinal cord injury. Rats were subjected to laminectomy and complete transection of their spinal cords (injury group) or laminectomy only (sham group). In the injury group, arginase I was increased in the macrophages at the transection edge, and the peak was observed 48 h after spinal cord injury. However, nitric oxide production decreased significantly in the injury group despite increased nitric oxide synthase2 mRNA expression compared with the sham group. We also demonstrated the reduction in L-arginine concentrations, which was inversely associated with changes in arginase activity. Therefore, arginase appeared to regulate nitric oxide production by consuming L-arginine. The regulation of arginase activity and L-arginine levels may improve nitroxidative stress and reduce tissue damage in spinal cord injury.

Plasma 249Ser p53 mutation in patients with hepatocellular carcinoma residing in a high risk area.

OBJECTIVE: To investigate plasma p53 mutation in hepatocellular carcinoma (HCC) patients from Qidong and to define its significance. METHODS: Blood samples from 25 hepatocellular carcinoma patients, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 microl of plasma from each sample. The 249(Ser) p53 mutation was detected by restriction digestion analysis and by direct sequencing of exon-7 PCR products. RESULTS: G-->T transversion at the third base of 249 codon resulting in 249(Arg)-->249(Ser) mutation in exon 7 of p53 gene were found in 11/25(44%) hepatocellular carcinoma cases, 4/20 (20%) cirrhotics, and 2/30 (7%) healthy controls (p<0.01). CONCLUSIONS: These data show that the 249(Ser) p53 mutation in plasma is strongly associated with hepatocellular carcinoma patients in Qidong area and the mutation should be screened as a new early diagnostic marker for HCC.

Expression and significance of new tumor suppressor gene PTEN in primary liver cancer.

OBJECTIVE: To investigate expression and significance of PTEN gene in primary hepatocellular carcinoma (HCC). METHODS: Immunohistochemical peroxidase-conjugated streptavidin (SP) method was used to detect expression of PTEN gene in 120 cases of primary HCC and its adjacent tissue 10 cases of normal liver tissue. The relationship between expression of tumor suppressor gene of PTEN and the percentage of lymph node metastasis of HCC was analyzed. RESULTS: It was shown that PTEN gene was expressed in all 10 cases of normal liver tissues and paracancerous liver tissues. The staining was localized mainly in cytoplasm. Expression of PTEN in 120 cases of HCC were as follows: 12.5% were negative, 17.5% were weak positive, and 70% were strong positive. At time of diagnosis, 33/120 (27.5%) presented lymph node metastasis. Lymph node metastases were present in 80% (12 out of 15) PTEN negative HCC, 57.14% (12 out of 21) PTEN weak positive HCC and only 10.71% (9 out of 84) PTEN intense positive HCC, (P<0.05). Therefore, PTEN tumor suppressor gene malfunction seems to be involved in metastasing capacity of HCC. CONCLUSION: This study suggests that PTEN gene was deleted or weakly expressed in primary hepatocellular carcinoma, which is probably related to its tumorigenesis.