Asialoglycoprotein receptor(ASGPR),also called galactose receptor,is predominantly expressed on the sinusoidal surface of mammalian hepatocytes and is involved in many physiological functions.For many years ASGPR has been applied for targeting hepatocytes in drug and gene delivery and for functional mapping of the liver,and considerable progress has been made.ASGPR-mediated liver-targeted drug delivery mainly involved anti-tumor drugs and cholesterol-lowering drugs,etc.Liver-targeted gene delivery was often seen in antisense drugs.The research of hepatic imaging mainly involved the evaluation of liver function and identification between hepatocellular carcinoma and hepatic metastasis of tumors.In addition,researchers have also extended its applications to some new fields,such as three-dimension culture of hepatocytes,hepatocytes screening,and hepatocytes transplantation.New achievements in studies of ASGPR-mediated liver targeting are reviewed in this article.

Disseminated malignancy is the main cause of cancer-related death.The spontaneous circulation of tumor cells is responsible for distant metastasis;therefore it is of potential importance to specifically and sensitively detect the circulating tumor cells,which not only allows for more accurate prediction of cancer prognosis,but also helps to tailor individualized anticancer treatment.This paper reviews the enrichment,detection and analyzing methods of circulating tumor cells.

Objective To assess the effectiveness of prenatal screening with maternal serum markers and the sonographic characteristics of the foetus for detecting trisomy 18. Methods Amniotic fluid or the fetal blood samples were obtained and cultured in women with positive results in serum screening (n=36) and with abnormal findings in sonography (n=92) at 18~32 weeks of gestation, and then fetal karyotyping was performed. Results Nine cases of trisomy 18 and 2 cases of other abnormal karyotype were found among the 128 pregnant women (8.59%, 11/128). Four cases were diagnosed as trisomy 18 among the 36 women with positive screening results. The rate of abnormal karyotype among those women with abnormal sonographic findings was 7.61%(7/92,5 cases of trisomy 18 and 2 cases of other abnormal karyotype). Two cases of trisomy 18 had both positive result in screening and abnormality in sonography. Conclusions Prenatal screening for maternal serum markers combined with sonographic examinations for the fetus is effective in detecting foetus with trisomy 18.

Objective To measure the value of orthopedic physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) and Portsmouth modified POSSUM (P-POSSUM) scoring systems in predicting operative risks in aged hip fracture patients.Methods Orthopedic POSSUM and P-POSSUM were performed to predict complication incidence and mortality for 164 aged patients operated for hip fracture.Validation of the scoring systems was tested by assessing observed to expected ratio,discrimination,and calibration.Discriminative ability and calibration of both scores were estimated using receiver operation characteristic curve (ROC) and Hosmer-Lemeshow test respectively.Results Orthopedic POSSUM score performed in predicting incidence of postoperative complications showed overall observed to expected ratio of 0.86,area under the curve of 0.82,and good calibration (H2 =3.66,df=8,P ＞ 0.05).P-POSSUM performed in predicting mortality showed overall observed to expected ratio of 0.80,area under the curve of 0.93 and good calibration (H2 =3.21,df =4,P ＞ 0.05).While orthopedic POSSUM overestimated postoperative mortality (overall observed to expected ratio =0.27).Conclusion Orthopedic POSSUM and P-POSSUM scores are respectively accurate in predicting postoperative complication incidence and mortality in aged hip fracture patients,but orthopedic POSSUM score overestimates the mortality.

Objective To assess hepatitis B virus(HBV)and hepatitis C virus(HCV)infections in different anatomic location of cholangiocarcinoma(CC)and relationship with abnormal p53 expression.Methods A total of 411 CC samples including intrahepatic cholangiocarcinoma(ICC 312 cases);perihilar cholangiocarcinoma(PHC,73 cases)and distal cholangiocarcinoma(DC,26 cases)underwent serologic test for HBsAg and anti-HCV using microparticle enzyme immunoassay.Abnormal p53 expression was detected in formalin-fixed.paraffin-embedded CC tissues by immunohistochemistry.Results Seropositivity for HBsAg and anti-HCV were found in 48.4%(151/312)and 2.9%(9/312)of ICC cases,and in 10.9%(8/73)and zero of PHC,and in 7.7%(2/26)and zero of DC,respectively.Abnormal p53 expression was detected in 30.1%(94/312)of ICC cases.23.3%(17/73)of PHC cases and 19.2%(5/26)of DC cases.There was no correlation between seropositivity of HBsAg and anti-HCV and p53 overexpression among three groups of CC. Conclusions HBV but not HCV infection may be associated with the development of ICC.p53 abnormality may not play a significant role in HBV-associated carcinogenesis of ICC.

Objective To investigate the risk factors of extrahepatie recurrences after curative resection of primary hepatocellular carcinoma (HCC). Methods Clinicopathologic data of 238 curative resected cases of primary HCC were retrospectively reviewed for parameters affecting postoperative extrahepatic recurrences. Results During a median follow-up of 34 months (7 - 78 months), extrahepatic recurrences were observed in 32 out of 238 patients (13.4%). According to univariate analysis, the risk factors for extrahepatic recurrences were preoperative serum a-fetoprotein (AFP) level of > 1000 ng/ml,aspartate aminotransferase level of > 50 IU/L, presence of hepatic vein invasion, neighboring organ invasion, tumor satellites, and lack of tumor capsule formation. Preoperative serum AFP levels of > 1000 ng/ml, hepatic vein invasion, neighboring organ invasion proved to be independent risk factors by multivariate analysis. Conclusions Extrahepatic recurrences after curative resection of HCC was found to be related to preoperative serum AFP level of > 1000 ng/ml, hepatic vein invasion, and neighboring organ invasion.

Objective To investigate influence of ginsenoside Rb1 on the proliferation and bioactivity of olfactory ensheathing cells (OECs).Methods OECs were primary cultured and purified from olfactory bulb of the adult SD rats.MTT assay was used to detect proliferation of OECs treated with ginsenoside Rb1 (intervention concentrations of 0,10,20,40,and 80 μg/ml and intervention time of 12,24,36,48,and 60 hours).Optimal concentration and intervention time of ginsenoside Rb1 was determined and performed in the succedent experiments.Purified cells were divided into blank control group and ginsenoside Rb1 group.RT-PCR was utilized to determine mRNA expressions of nerve growth factor (NGF),brain-derived neurotrophic factor (BDNF),glial derived neurotrophic factor(GDNF) and neural cell adhesion molecule (N-CAM) in the two groups.ELISA analysis was performed to measure secretion levels of NGF,BDNF and GDNF in the cultural supernatant.Results MTF analysis suggested ginsenoside Rb1 promoted proliferation of OECs with optimal effect at 20 μg/ml concentration for 48 hours (0.648±0.019,P ＜ 0.05).RT-PCR analysis demonstrated that mRNA expressions of NGF,BDNF,GDNF and N-CAM were significantly up-regulated in ginsenoside Rb1 group compared to those in blank control group (0.620 ± 0.011 vs 0.180 ± 0.011,0.511 ± 0.090 vs 0.293 ± 0.051,0.343 ± 0.042 vs 0.064 ± 0.005,0.839 ± 0.017 vs 0.717 ± 0.044) (P ＜ 0.05).ELISA analysis confirmed that secretions of NGF,BDNF and GDNF was increased in Rb1 group compared to those in blank control group (200.167 ± 8.361 vs 51.467 ± 3.815,156.700 ± 4.190 vs 96.500 ± 2.707,26.264 ± 5.864 vs 4.917 ± 10.894,P ＜ 0.05).Conclusion Ginsenoside Rb1 significantly promotes proliferation and bioactivity of OECs and hence benefits to spinal cord injury repair.

Objective To study the effect of Pleurotus eryngii polysaccharide on aging mice induced by D-galactose (D-gal). Methods 72 ICR mice were divided into high, moderate, and low dosages (of polysaccharide) groups, piracetam group, model group, and control group, 12 in each group. The model of aging mice was induced with D-gal. They were tested with Y-maze, and the contents of superoxide dismutase (SOD), malondialdehyde (MDA), lipofuscin and L-glutamate in cerebrum were determined 6 weeks after model. Results Compared with the model group, the achievement of Y-maze improved, the activities of SOD increased and the content of MDA and lipofuscin decreasd in high and moderate dosage groups (P<0.05), while the mass of brain and kidney increased and the L-glutamate decreased in the high dosage group (P<0.05). Conclusion Pleurotus eryngii polysaccharide can ameliorate aging of mice induced by D-gal.

Objectives To study the mutation spectrum in CYP21A2 gene in patients with 21-hydroxylase deficiency (21-OHD), and to analyze the relationship between genotype and phenotype. Methods Eighteen patients with 21-OHD were identified by neonatal screening of 17α-OH progesterone (17α-OHP). The allele specific PCR-DNA sequencing com-bining with multiplex ligation-dependent probe amplification was applied to determine the genotype in the patients and their parents. Results Six mutations of CYP21A2 gene were identified. I2G (44.4%) and del (33.3%) were the most frequent mutations and also were the most common mutations in salt-wasting form. The detection rate of I172N mutation in simple virilizing form was 75%. Patients were classified into three groups according to the degree of 21-hydroxylase enzymatic compromise caused by the mutation. The serum 17α-OHP, ACTH and T levels which reflected the severity of disease were significantly different among three groups (P<0.05). Conclusions The genetic diagnosis of 21-OHD reveals the consistency between genotype and phenotype.

Objective To develop and validate a method for detecting factor 8 gene (F8) mutations in hemophilia A patients by Ion Torrent semiconductor sequencing .Methods Intron 22 and intron 1 inversions of F8 gene were identified by long distance PCR (LD-PCR), other mutations in the F8 gene were identified by Ion Torrent sequencing.Candidate variants were validated by Sanger sequencing .Sanger sequencing was applied to screen HA carriers from 11 female family members in the 8 pedigrees.One pregnant woman was offered prenatal diagnosis via analyzing the fetal DNA obtained through amniocentesis . Results Four missense mutations ( c.1331A >C, 1648C >T, c.6506G >A, c.6544C >T), two frameshift mutations ( c.2393 _2394insT, c.6320delG), one splicing mutation ( IVS5 +5G >A), one nonsense mutation (c.43C >T) and one Inv22 mutation were identified in all nine probands respectively . Among 11 female family members, 10 females were identified to be HA carriers, and one didn′t carry the maternal pathogenic mutation.Prenatal diagnosis result showed that the fetus inherited the wild -type maternal allele and was predicted to be unaffected by HA .Conclusion The targeted Ion Torrent sequencing is a reliable and efficient method to detect F8 mutations in patients with Hemophilia A disease .