Vitamin D 1,25-Dihydroxyvitamin D_(3) reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization

BACKGROUND Non-alcoholic fatty liver disease(NAFLD),which is a significant liver condition associated with metabolic syndrome,is the leading cause of liver diseases globally and its prevalence is on the rise in most nations.The protective impact of vitamin D on NAFLD and its specific mechanism remains unclear.AIM To examine the role of vitamin D in NAFLD and how vitamin D affects the polarization of hepatic macrophages in NAFLD through the vitamin D receptor(VDR)-peroxisome proliferator activated receptor(PPAR)γpathway.METHODS Wild-type C57BL/6 mice were provided with a high-fat diet to trigger NAFLD model and administered 1,25-dihydroxy-vitamin D[1,25(OH)_(2)D_(3)]supplementation.1,25(OH)_(2)D_(3) was given to RAW264.7 macrophages that had been treated with lipid,and a co-culture with AML12 hepatocytes was set up.Lipid accumulation,lipid metabolism enzymes,M1/M2 phenotype markers,proinflammatory cytokines and VDR-PPARγpathway were determined.RESULTS Supplementation with 1,25(OH)_(2)D_(3) relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD.Administration of 1,25(OH)_(2)D_(3) suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids,thereby directly relieving lipid accumulation and metabolism in hepatocytes.The VDR-PPARγpathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)_(2)D_(3).CONCLUSION Supplementation with 1,25(OH)_(2)D_(3) improved hepatic steatosis and lipid metabolism in NAFLD,linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages,partially by regulating the VDRPPARγpathway.The involvement of 1,25(OH)_(2)D_(3) in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.

Modelling smear effect of vertical drains using a diameter reduction method

Vertical drains are used to accelerate consolidation of clays in ground improvement projects.Smear zones exist around these drains,where permeability is reduced due to soil disturbance caused by the installation process.Hansbo solution is widely used in practice to consider the effects of drain discharge capacity and smear on the consolidation process.In this study,a computationally efficient diameter reduction method(DRM)obtained from the Hansbo solution is proposed to consider the smear effect without the need to model the smear zone physically.Validated by analytical and numerical results,a diameter reduction factor is analytically derived to reduce the diameter of the drain,while achieving similar solutions of pore pressure dissipation profile as the classical full model of the smear zone and drain.With the DRM,the excess pore pressure u obtained from the reduced drain in the original un-disturbed soil zone is accurate enough for practical applications in numerical models.Such performance of DRM is independent of soil material property.Results also show equally accurate performance of DRM under conditions of multi-layered soils and coupled radial-vertical groundwater flow.

Perceived Barriers to Cervical Cancer Screening Using Pap Smear Test among Women Attending Saad Abu Al Ella Hospital in Khartoum State, 2022

Background: Cervical cancer is the second common cancer among women worldwide. It is a preventable cancer, and early detection of precancerous conditions through the Papanicolaou cytology screening (Pap smear) is a key aspect of prevention;it is accepted worldwide as an efficient tool for secondary prevention. While the PS test is simple, inexpensive, and relatively reliable as a method of diagnosing cervical cancer, most women do not take the test. Therefore, this study is sought to describe the barriers to pap smear uptake among Sudanese women. Materials and Method: This total coverage observational, analytical and cross sectional, hospital-based study was conducted in Saad Abu El Ella Hospital in April 2022. The study was conducted using an anonymous questionnaire to assess the perceived barriers of 93 participants. All data were computerized using Microsoft Excel’17 and the data were described and analyzed using statistical package for social science (SPSS23). Results: The findings revealed that the mean age of the participants was 39.5 years and only 3.2% had ever undergone a pap smear test. Identified barriers were lack of information, not knowing where to go, and fear of pain. The majority, 72% are willing to routinely perform a pap smear test if well informed about it. The study also demonstrates that there is a significant correlation between perceived barriers score and willingness to perform the pap smear test (p value = 0.008), and between the perceived barriers score and the sociodemographic factors: Age (p value = 0.006), educational level (p value = 0.028) and occupation (p value = 0.040), but no association with the economic status was found (p value = 0.378). Conclusion: The detection rate is too low compared to the national target of over 70%. Therefore, more work is needed to reduce perceived barriers to cervical cancer screening by providing education/raising for popular awareness;addressing misconceptions and false beliefs;informing women about the necessity and importance of Pap smear;and health promotion using mass media such as national television, social media, radio, billboards, and newspapers and other print media.

MayGAN:Mayfly Optimization with Generative Adversarial Network-Based Deep Learning Method to Classify Leukemia Form Blood Smear Images

Leukemia,often called blood cancer,is a disease that primarily affects white blood cells(WBCs),which harms a person’s tissues and plasma.This condition may be fatal when if it is not diagnosed and recognized at an early stage.The physical technique and lab procedures for Leukaemia identification are considered time-consuming.It is crucial to use a quick and unexpected way to identify different forms of Leukaemia.Timely screening of the morphologies of immature cells is essential for reducing the severity of the disease and reducing the number of people who require treatment.Various deep-learning(DL)model-based segmentation and categorization techniques have already been introduced,although they still have certain drawbacks.In order to enhance feature extraction and classification in such a practical way,Mayfly optimization with Generative Adversarial Network(MayGAN)is introduced in this research.Furthermore,Generative Adversarial System(GAS)is integrated with Principal Component Analysis(PCA)in the feature-extracted model to classify the type of blood cancer in the data.The semantic technique and morphological procedures using geometric features are used to segment the cells that makeup Leukaemia.Acute lymphocytic Leukaemia(ALL),acute myelogenous Leukaemia(AML),chronic lymphocytic Leukaemia(CLL),chronic myelogenous Leukaemia(CML),and aberrant White Blood Cancers(WBCs)are all successfully classified by the proposed MayGAN model.The proposed MayGAN identifies the abnormal activity in the WBC,considering the geometric features.Compared with the state-of-the-art methods,the proposed MayGAN achieves 99.8%accuracy,98.5%precision,99.7%recall,97.4%F1-score,and 98.5%Dice similarity coefficient(DSC).

Histogram-Based Decision Support System for Extraction and Classification of Leukemia in Blood Smear Images

An abnormality that develops in white blood cells is called leukemia.The diagnosis of leukemia is made possible by microscopic investigation of the smear in the periphery.Prior training is necessary to complete the morphological examination of the blood smear for leukemia diagnosis.This paper proposes a Histogram Threshold Segmentation Classifier(HTsC)for a decision support system.The proposed HTsC is evaluated based on the color and brightness variation in the dataset of blood smear images.Arithmetic operations are used to crop the nucleus based on automated approximation.White Blood Cell(WBC)segmentation is calculated using the active contour model to determine the contrast between image regions using the color transfer approach.Through entropy-adaptive mask generation,WBCs accurately detect the circularity region for identification of the nucleus.The proposed HTsC addressed the cytoplasm region based on variations in size and shape concerning addition and rotation operations.Variation in WBC imaging characteristics depends on the cytoplasmic and nuclear regions.The computation of the variation between image features in the cytoplasm and nuclei regions of the WBCs is used to classify blood smear images.The classification of the blood smear is performed with conventional machine-learning techniques integrated with the features of the deep-learning regression classifier.The designed HTsC classifier comprises the binary classifier with the classification of the lymphocytes,monocytes,neutrophils,eosinophils,and abnormalities in the WBCs.The proposed HTsC identifies the abnormal activity in the WBC,considering the color and shape features.It exhibits a higher classification accuracy value of 99.6%when combined with the other classifiers.The comparative analysis expressed that the proposed HTsC model exhibits an overall accuracy value of 98%,which is approximately 3%–12%higher than the conventional technique.

Dexamethasone potentiates the insulin-induced Srebp-1c expression in primary rat hepatocytes

The impacts of dexamethasone(Dex)and thyroid hormone T3 on the insulin-stimulated Srebp-1c expression were studied in primary rat hepatocytes. Primary hepatocytes from Sprague-Dawley rats were isolated, cultured and treated with insulin in the presence or absence of the indicated reagents over time. The mRNA levels of indicated genes were determined using real-time PCR. Insulin treatment induced the Srebp-1c expression and suppressed the Pck1 expression in a time-dependent manner. Dex treatment alone reduced the Srebp-1c expression, whereas potentiated the insulin-induced its expression, which reached to a level that was higher than the insulin alone group. On the other hand, insulin treatment completely suppressed the Dex-induced Pck1 expression in the same cells. T3 treatment did not affect the expressions of Srebp-1c and Pck1 alone or in the presence of absence of insulin or Dex. Interestingly, insulin treatment induced the Rxrg m RNA expression level in the absence or presence of T0901317, a specific agonist for the liver X receptor. Dex and insulin mutually affect each other's ability to regulate the expression levels of hepatic genes involved in glucose and fatty acid metabolism. Insulin induced Rxrg expression in primary hepatocytes, which may contribute to the induction of Srebp-1c expression in the same cells.

Qualitative Abnormalities of Peripheral Blood Smear Images Using Deep Learning Techniques

In recent years,Peripheral blood smear is a generic analysis to assess the person’s health status.Manual testing of Peripheral blood smear images are difficult,time-consuming and is subject to human intervention and visual error.This method encouraged for researchers to present algorithms and techniques to perform the peripheral blood smear analysis with the help of computer-assisted and decision-making techniques.Existing CAD based methods are lacks in attaining the accurate detection of abnormalities present in the images.In order to mitigate this issue Deep Convolution Neural Network(DCNN)based automatic classification technique is introduced with the classification of eight groups of peripheral blood cells such as basophil,eosinophil,lymphocyte,monocyte,neutrophil,erythroblast,platelet,myocyte,promyocyte and metamyocyte.The proposed DCNN model employs transfer learning approach and additionally it carries three stages such as pre-processing,feature extraction and classification.Initially the pre-processing steps are incorporated to eliminate noisy contents present in the image by using Histogram Equalization(HE).It is enclosed to improve an image contrast.In order to distinguish the dissimilar class and segmentation approach is carried out with the help of Fuzzy C-Means(FCM)model whereas its centroid point optimality method with Slap Swarm based optimization strategy.Moreover some specific set of Gray Level Co-occurrence Matrix(GLCM)features of the segmented images are extracted to augment the performance of proposed detection algorithm.Finally the extracted features are recorded by DCNN and the proposed classifier has the capability to extract their own features.Based on this the diverse set of classes are classified and distinguished from qualitative abnormalities found in the image.

Cyclic feeding regime may delay aging in animals by enhancing the hepatocytes nuclei structure

Background:The liver is fundamental for keeping up the entire body’s homeostasis.The liver hepatocytes have been shown to undergo genomic instability with aging.The stability of the hepatocytes depends on its nuclear architecture.Calorie restriction has been shown to extend life-span favorably and this may be through the reorganization of the nuclear structure.Objective:To study the effect of cyclic feeding regime on the chromatin assembly anchored to the nuclear membrane scaffold of rat models hepatocytes nuclei.Method:Rats models underwent cyclic feeding regime,after which nuclei were isolated;then,we investigated the chromatin decondensation and nuclear membrane disintegration of the hepatocytes using fluorescence imaging methods.Results:In 60 seconds,protease decondensed the chromatin and disintegrated the nuclear membrane structure of controls.After the first fasting,the time increased to 145 seconds in 3-month-old rats.The first refeeding increased the time to 156 seconds with a further rise to 340 seconds following the second fasting,then dropped to 116 seconds by the second refeeding.20 months old rats showed 186 seconds increase in the time of chromatin decondensation and nuclear membrane disintegration after the first fasting,with a decrease to 140 seconds observed after first refeeding.The second fasting increased the time to 165 seconds,which then slightly decreased to 163 seconds after the second refeeding.Conclusion:These results show that intermittent fasting may have acted on chromatin histone interactions and the structural lamin networks of the nuclear membranes in bringing about nuclear stability,which is essential for normal cellular function.

An online identity authentication method for blood smear

Blood smear test is the basic method of blood cytology and is also a standard medical test that can help diagnose various conditions and diseases.Morphological examination is the gold stan-dard to determine pathological changes in blood cell morphology.In the biology and medicine automation trend,blood smears'automated management and analysis is very necessary.An online blood smear automatic microscopic image detection system has been constructed.It includes an online blood smear automatic producing part and a blood smear automatic micro-scopic image detection part.Online identity authentication is at the core of the system.The identifiers printed online always present dot matrix digit code(DMDC)whose stroke is not continuous.Considering the particularities of DMDC and the complexities of online application environment,an online identity authentication method for blood smear with heterological theory is proposed.By synthesizing the certain regional features according to the heterological theory,high identification accuracy and high speed have been guaranteed with few features required.In the experiment,the suficient correct matches bet ween the tube barcode and the identification result verified its feasibility and validity.

Reversible immortalization of human hepatocytes mediated by retroviral transfer and site-specific recombination

AIM: To establish a method for the reversible immortalization of human hepatocytes, which may offer a good and safe source of hepatocytes for practical applications.

Effects of Fluoride on Lipid Peroxidation, DNA Damage and Apoptosis in Human Embryo Hepatocytes

Objective To investigate the effects of fluoride on lipid peroxidation, DNA damage and apoptosis in human embryo hepatocyte L-02 cells. Methods Lipid peroxide (LPO) level, reduced glutathione (GSH) content, DNA damage, apoptosis, and cell cycle analysis were measured after in vitro cultured L-02 cells were exposed to sodium fluoride at different doses (40 μg/mL, 80 μg/mL, and 160 μg/mL) for 24 hours. Results Fluoride caused an increase of LPO levels and a decrease of GSH content in L-02 cells. There appeared to be an obvious dose-effect relationship between the fluoride concentration and the observed changes. Fluoride also caused DNA damage and apoptosis and increased the cell number in S phase of cell cycle in the cells tested. There was a statistically significant difference in DNA damage and apoptosis when comparing the high dose of fluoride treated cells with the low dose of fluoride treated cells. Conclusion Fluoride can cause lipid peroxidation, DNA damage, and apoptosis in the L-02 cell experimental model and there is a significant positive correlation between fluoride concentration and these pathological changes.

Effects of Fuzhenghuayu decoction on collagen synthesis of cultured hepatic stellate cells,hepatocytes and fibroblasts in rats

AIM To study the mechanism of Fuzhenghuayu (FZHY) decoction on anti liver fibrosis. METHODS FZHY 10% decoction sera was incubated with rat normal subcultured hepatic stellate cells (HSC) and fibrotic primarily cultured HSC, normal and fibrotic hepatocytes and subcultured skin fibroblasts separately. Cell intracellular and extracellular collagen synthesis rates were measured by the method of Proline impulse and collagenase digestion. RESULTS For primarily cultured HSC and hepatocytes, both of intracellular and extracellular collagen synthesis rates decreased in the drug sera group. For the normal subcultured HSC and primarily cultured hepatocytes, the extracellular collagen secretion was decreased obviously by the drug sera, and intracellular collagen synthesis rates were inhibited to some extents. For fibroblasts, both intracellular and extracellular collagen synthesis rates were inhibited some what, but no significant differences were found. CONCLUSION The mechanism of FZHY decoction on anti liver fibrosis may be associated with inhibition of liver collagen production.

Assessing the anti-estrogenic activity of sodium pentachlorophenol in primary cultures of juvenile goldfish (Carassius auratus) hepatocytes using vitellogenin as a biomarker

Both pentachlorophenol and 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） had been studied widely because of their probable anti-estrogenic activity. Sodium pentachlorophenol （PCP-Na）, as a industrial product used in many fields, usually contains a trace of TCDD. The aim of this study was to assess the anti-estrogenic effect of PCP-Na in juvenile goldfish （Gurassius auratus） hepatocyte cultures using vitellogenin （VTG） as the biomarker. The ID50 of PCP-Na was investigated and then a series of concentrations （0.001 0.5 μg/ml） of PCP-Na were evaluated to estimate the anti-estrogenic activity. Results showed that PCP-Na was cytotoxic for hepatocytes even at very low concentration 〈1.21 μg/ml, and it could not induce VTG at any concentrations tested. Since it failed to stimulate VTG production, the possibility of its anti-estrogenic effect was tested, and a well-known anti-estrogenic compound-tamoxifen was used as positive control. PCP-Na caused a reduction in VTG synthesis in juvenile goldfish （Carassius auratus） hepatocytes at concentrations 〉0.1μg/ml when co-exposure with 1μg/ml 17β-estradiol （E2）, making its anti-estrogenic activity approximately as potent as tamoxifen. Our results indicate that PCP-Na can act as negative modulators of estrogenic function in juvenile goldfish （Carassius auratus） hepatocytes.

Primary porcine hepatocytes with portal vein serum cultured on microcarriers or in spheroidal aggregates

AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with collagenase.In culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)respectively.Inspheroidal aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/mL.RESULTS In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being inoculated.Typical multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere cultured.The morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture system.In spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μm.The relationship among thehepatocytes resembled that in the liver in vivo.Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytescultured on monolayers.CONCLUSION As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.

Prostaglandin E1 protects hepatocytes against endoplasmic reticulum stress-induced apoptosis via protein kinase A-dependent induction of glucose-regulated protein 78 expression

AIM To investigate the protective effect of prostaglandin E1(PGE1) against endoplasmic reticulum(ER) stressinduced hepatocyte apoptosis, and to explore its underlying mechanisms.METHODS Thapsigargin(TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinomaderived cell line Hep G2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RTPCR. Apoptotic index and cell viability of L02 cells and Hep G2 cells were determined with flow cytometry and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium] assay. RESULTS Pretreatment with 1 μmol/L PGE1 protected against TG-induced apoptosis in both L02 cells and Hep G2 cells. PGE1 enhanced the TG-induced expression of C/EBP homologous protein(CHOP), glucose-regulated protein(GRP) 78 and spliced X box-binding protein 1 at 6 h. However, it attenuated their expressions after 24 h. PGE1 alone induced protein and m RNA expressions of GRP78; PGE1 also induced protein expression of DNA damage-inducible gene 34 and inhibited the expressions of phospho-PKR-like ER kinase, phosphoeukaryotic initiation factor 2α and CHOP. Treatment with protein kinase A(PKA)-inhibitor H89 or KT5720 blocked PGE1-induced up-regulation of GRP78. Further, the cytoprotective effect of PGE1 on hepatocytes was not observed after blockade of GRP78 expression by H89 or small interfering RNA specifically targeted against human GRP78.CONCLUSION Our study demonstrates that PGE1 protects against ER stress-induced hepatocyte apoptosis via PKA pathwaydependent induction of GRP78 expression.

How hepatitis C virus invades hepatocytes: The mystery of viral entry

Hepatitis C virus(HCV)infection is a global health problem,with an estimated 170 million people being chronically infected.HCV cell entry is a complex multi-step process,involving several cellular factors that trigger virus uptake into the hepatocytes.The high-density lipoprotein receptor scavenger receptor class B type I,tetraspanin CD81,tight junction protein claudin-1,and occludin are the main receptors that mediate the initial step of HCV infection.In addition,the virus uses cell receptor tyrosine kinases as entry regulators,such as epidermal growth factor receptor and ephrin receptor A2.This review summarizes the current understanding about how cell surface molecules are involved in HCV attachment,internalization,and membrane fusion,and how host cell kinases regulate virus entry.The advances of the potential antiviral agents targeting this process are introduced.

Isolation and primary culture of rat hepatocytes

Objective: To find out an optimal condition for isola-tion and primary culture of hepatocytes.Method: Rat hepatocytes were isolated by a two-stepcollagenase perfusion, and cultured in hepatozyme-SFM. The reduction of MTT to formazan salt was ex-amined. Supernatant medium was collected for analy-sis of alanine aminotransferase（ALT） and ureagene-sis.Results: The two-step collagenase perfusion yielded39±12×10;cells/g liver tissue with a viability of88%±2%. Fine morphology and stable urea synthesisfor one week could be achieved when hepatocytes werecultured in Hepatozyme-SFM.Conclusion: High yield of hepatocytes can be isolatedwith two-step collagenese perfusion. Hepatozyme-SFM is suitable for sustained growth of hepatocytes.

Induction of Heme Oxygenase-1 in Human Hepatocytes to Protect Them From Ethanol-induced Cytotoxicity

Background/Aim We investigated the relationship between ethanol exposure and heme oxygenase (HO-1) in human hepatocytes in order to ascertain if induction of HO-1 can prevent ethanol induced cellular damage. Methods Dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) ethanol exposure were used in the present study. HO-1 mRNA and protein expression were detected by PT-PCR and Western blot respectively. HO-1 activity was indicated by bilirubin and Fe2+ formation. Cytotoxicity was investigated by means of lactate dehydrogenate (LDH) and aspartate transaminase (AST) level in culture supernatants, as well as the intracellular formation of malondialdehyde (MDA), cellular glutathione (GSH) status and CYP 2E1 activity. Results We first demonstrated a dose-dependent response between ethanol exposure and HO-1 mRNA and protein expression in human hepatocytes. We further observed a time-dependent increase of HO-1 mRNA expression using 100 mmol/L ethanol starting 30 minutes after ethanol exposure, reaching its maximum between 3 h and 9 h. Being similar to what had been demonstrated with the mRNA level, increased protein expression started at 6 h after ethanol exposure, and kept continuous elevated over 18 h. In addition, we found that ethanol exposure to hepatocytes markedly increased HO-1 enzyme activity in a time-dependent manner measured as bilirubin and Fe2+ formation in human hepatocytes. Our results clearly showed that ethanol exposure caused a significant increase of LDH, AST, and MDA levels, while the antioxidant GSH was time-dependently reduced. Furthermore, we demonstrated that pre-administration of cobalt protoporphyrin (CoPP) induced HO-1 in human hepatocytes, and prevented an increase of MDA and a decrease of GSH. These effects could be partially reversed by zinc protoporphyrin (ZnPP), an antagonist of HO-1 induction. Conclusion HO-1 expression in cells or organs could lead to new strategies for better prevention and treatment of ethanol-induced oxidative damage in human liver.

Study on liver targeting and hepatocytes permeable valaciclovir polybutylcyanoacrylate nanoparticles *

AIM To prepare valaciclovir polybutylcyan_ oacrylate nanoparticles (VACV PBCA NP) with liver targeting and hepatocyte permeable characteristics. METHODS Emulsion polymerization method was employed to prepare VACV PBCA NP. The formula and preparation conditions were optimized by using the uniform design. The organ distribution of the intravenously injected VACV PBCA NP and VACV in animal was determined using HPLC. The hepatocytes permeability of VACV PBCA NP was demonstrated by cell uptake experiment in vitro . RESULTS The drug loading and the drug embedding ratio of VACV PBCA NP were 11 20% and 84 85% respectively, with an average diameter of 104 77nm ± 11 78nm . The releasing characteristics in vitro fitted the two phase kinetics. 74 49% of the drug was found to localize in the liver 15min after the administration of VACV PBCA NP in the mice. Compared with VACV, VACV PBCA NP showed distinct characteristic of sustained release in vivo and the drug entering hepatocytes were also greatly increased. CONCLUSION VACV PBCA NP has the char_ acteristic of liver targeting and can increase the permeability of VACV to hepatocytes.