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Objective:To study the expressions of heat shock protein (HSP) 90α and HSP90β in colorectal cancer and paracancer tissues, and to investigate the relationships between HSP90α, HSP90β and clinicopathological features of colorectal cancer patients, and to analyze their correlation.Methods:The tumor tissues and paracancer tissues of 117 patients with colorectal cancer were selected from the Department of Gastrointestinal Surgery, Third Affiliated Hospital of Shandong First Medical University from January 2016 to December 2020. The expression levels of HSP90α and HSP90β were detected by immunohistochemistry, and the relationships between the two proteins and clinicopathological features and the correlation of their expressions were analyzed.Results:The positive expression rates of HSP90α in colorectal cancer tissues and paracancer tissues were 74.4% (87/117) and 12.0% (14/117) , and there was a statistically significant difference ( χ2=92.83, P<0.001) . The positive expression rate of HSP90β in colorectal cancer tissues and paracancer tissues was 61.5% (72/117) and 10.3% (12/117) , and there was a statistically significant difference ( χ2=66.86, P<0.001) . The expression of HSP90α was correlated with tumor location ( χ2=8.67, P=0.003) , vascular invasion ( χ2=8.68, P=0.003) , lymph node metastasis ( χ2=8.52, P=0.004) , T stage ( χ2=21.07, P<0.001) , N stage ( χ2=11.94, P=0.003) , M stage ( χ2=5.37, P=0.020) , pathological stage ( χ2=25.64, P<0.001) . The expression of HSP90β was correlated with lymph node metastasis ( χ2=4.03, P=0.045) , T stage ( χ2=11.09, P=0.007) , N stage ( χ2=6.56, P=0.038) , M stage ( χ2=12.43, P<0.001) , pathological stage ( χ2=17.34, P=0.001) . There was a positive correlation between the expressions of the two proteins in colorectal cancer tissues ( r=0.42, P<0.001) . Conclusion:The expressions of HSP90α and HSP90β in colorectal cancer tissues are significantly higher than those in paracancer tissues, and they are related to lymph node metastasis and pathological stage. There is a positive correlation between the two proteins, which may be involved in the occurrence and development of colorectal cancer and are expected to become new tumor markers.
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Objective@#To investigate the effects of Helicobacter pylori (HP) radical treatment on diagnosis of early gastric cancer using conventional white light endoscopy (WLE), chromoendoscopy of indigo carmine dye added to acetic acid, and magnifying endoscopy with narrow band imaging (ME-NBI).@*Methods@#Between January 2013 and March 2018, patients without HP (successful cured before six months) or with HP (no radical treatment for HP in recent 6 months), who underwent endoscopy examinations in the Department of Gastroenterology of Ezhou Hospital, People′s Hospital of Wuhan University or the Department of Gastroenterology of Union Hospital, Tongji Medical College Huazhong University of Science and Technology were enrolled in the study. Endoscopy examinations were performed according to the order of conventional WLE, chromoendoscopy using indigo carmine dye added to acetic acid, and ME-NBI. Among the patients finally diagnosed as early gastric cancer by histopathology, 120 patients without HP and 120 patients with HP were continuously collected, and included in the radical treatment group and the non-radical treatment group, respectively. Diagnostic reliabilities of WLE, chromoendoscopy, and ME-NBI for early gastric cancer between the two groups were statistically analyzed.@*Results@#There were no statistical differences between the two groups in terms of hospital source (χ2=2.637, P=0.104), gender composition (χ2=0.074, P=0.785), mean age (t=0.582, P=0.561), and lesion morphology (χ2=0.179, P=0.914). The detection rates of early gastric cancer in the radical treatment group using WLE [75.0% (80/120) VS 81.7% (98/120), χ2=7.046, P=0.008], chromoendoscopy [57.5% (69/120) VS 93.3% (112/120), χ2=41.554, P<0.001], and ME-NBI [90.0% (108/120) VS 98.3% (118/120), χ2=7.585, P=0.006] were significantly lower than those in the non-radical treatment group. In the radical treatment group, chromoendoscopy had the lowest detection rate of early gastric cancer, followed by WLE (χ2=2.142, P=0.143) and ME-NBI (χ2=32.736, P<0.001), while ME-NBI had the highest detection rate of early gastric cancer, which higher than that of WLE (χ2= 19.247, P<0.001).@*Conclusion@#The diagnosis of early gastric cancer by WLE, chromoendoscopy using the indigo carmine dye added to acetic acid and ME-NBI becomes more difficult after radical treatment of HP. Among the above three endoscopic methods, ME-NBI has the highest diagnostic efficacy, and becomes the first choice for the clinical diagnosis of early gastric cancer after radical treatment of HP.
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Objective To investigate the effects of Helicobacter pylori (HP) radical treatment on diagnosis of early gastric cancer using conventional white light endoscopy ( WLE ) , chromoendoscopy of indigo carmine dye added to acetic acid, and magnifying endoscopy with narrow band imaging (ME-NBI). Methods Between January 2013 and March 2018, patients without HP (successful cured before six months) or with HP ( no radical treatment for HP in recent 6 months ) , who underwent endoscopy examinations in the Department of Gastroenterology of Ezhou Hospital, People's Hospital of Wuhan University or the Department of Gastroenterology of Union Hospital, Tongji Medical College Huazhong University of Science and Technology were enrolled in the study. Endoscopy examinations were performed according to the order of conventional WLE, chromoendoscopy using indigo carmine dye added to acetic acid, and ME-NBI. Among the patients finally diagnosed as early gastric cancer by histopathology, 120 patients without HP and 120 patients with HP were continuously collected, and included in the radical treatment group and the non-radical treatment group, respectively. Diagnostic reliabilities of WLE, chromoendoscopy, and ME-NBI for early gastric cancer between the two groups were statistically analyzed. Results There were no statistical differences between the two groups in terms of hospital source (χ2 =2. 637, P=0. 104) , gender composition (χ2=0. 074, P=0. 785) , mean age ( t=0. 582, P=0. 561) , and lesion morphology (χ2 = 0. 179, P= 0. 914 ) . The detection rates of early gastric cancer in the radical treatment group using WLE [ 75. 0％( 80/120 ) VS 81. 7％( 98/120 ) ,χ2 = 7. 046, P = 0. 008 ] , chromoendoscopy [ 57. 5％( 69/120 ) VS 93. 3％( 112/120 ) ,χ2 =41. 554, P<0. 001 ] , and ME-NBI [ 90. 0％( 108/120) VS 98. 3％( 118/120) ,χ2=7. 585, P=0. 006] were significantly lower than those in the non-radical treatment group. In the radical treatment group, chromoendoscopy had the lowest detection rate of early gastric cancer, followed by WLE (χ2=2. 142, P=0. 143) and ME-NBI (χ2=32. 736, P<0. 001) , while ME-NBI had the highest detection rate of early gastric cancer, which higher than that of WLE (χ2= 19.247, P<0.001). Conclusion The diagnosis of early gastric cancer by WLE, chromoendoscopy using the indigo carmine dye added to acetic acid and ME-NBI becomes more difficult after radical treatment of HP. Among the above three endoscopic methods, ME-NBI has the highest diagnostic efficacy, and becomes the first choice for the clinical diagnosis of early gastric cancer after radical treatment of HP.
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Objective To investigate the changes of cortical thickness and relative resting state functional connectivity in patients with generalized anxiety disorder (GAD).Methods The present study analyzed structural and eyes-open resting state functional MRI were performed in 21 patients with GAD and 22 matched healthy controls.Cortical thickness was estimated with FreeSurfer.The structurally altered regions were defined as region of interest (ROI) to analyze functional connectivity (FC) using resting state functional MRI data by DPABI.Results Cortical thickness of patients with GAD were increased in right rostral middle frontal gyrus (rMFG;MNI:x =27.9,y =53.4,z =-11.1;size:241.93 mm2;FDR corrected,P ＜ 0.1) and right inferior temporal gyrus (IGT;MNI:x =49.7,y =-57.8,z =-8.7;size:138.93 mm2;FDR corrected,P＜0.1) compared with healthy controls.FC between right rMFG and right superior/middle occipital gyrus as well as well as FC between rMFG and right precentral gyrus showed decreased in patients with GAD compared with healthy controls(AlphaSim corrected,P＜0.05).FC between right rMFG and right angular gyrus showed increased in patients with GAD compared with healthy control (AlphaSim corrected,P＜0.05).Conclusion The rMFG may play an important role in the pathophysiology of GAD,which can be used as an stimuli target in physicotherapeutics to improve anxiety symptoms.
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Objective To explore the natural courses of 11 patients with cesarean scar pregnancy (CSP) with expectant management. Methods Eleven patients with CSP who were diagnosed in the first trimester in the Third Affiliated Hospital of Guangzhou Medical University from January 2015 to March 2017 were recruited. All of them received expectant management. Nine pregnancies continued to the third trimester (the third trimester group), and 2 patients were expected to the second trimester (the second trimester group). The gestational age at diagnosis, CSP type, gravidity, parity, miscarriage and previous cesarean section history, gestational weeks at termination, amount of postpartum hemorrhage, prenatal and postnatal hemoglobin levels, pregnancy outcomes and obstetric complications were compared between the two groups. Results The third trimester group terminated pregnancies between 33 + 2 and 36 + 5 weeks. The second trimester group terminated in the second trimester because of rupture of uterus (at 17+2,17+3 weeks). There was no statistical difference between the two groups regarding the number of gravidity, parity and previous cesarean section(all P>0.05). The number of miscarriage in the second trimester group was 4.0 ± 2.8,and in the third trimester group was 1.3 ± 1.1(P<0.05). In the third trimester group, 7 cases were CSP typeⅠand 2 cases were CSPⅡ. In the second trimester group, 2 cases were both CSP typeⅢ. Eleven cases were diagnosed placenta accreta pathologically. There was no maternal death,and 6 cases received hysterectomy (6/11). The amount of postpartum hemorrhage increased remarkably and all neonates survived (pregnancy terminated between 33+2 and 36+5 weeks). Conclusions For those diagnosed as CSP typeⅠandⅡwho urge to continue pregnancies, it′s plausible to have expectant management with fully consent of obstetric hemorrhage, rupture of uterus and hysterectomy and close monitoring in tertiary hospital. The detailed expectant management of CSP is needed further exploration.
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Objective To explore the natural courses of 11 patients with cesarean scar pregnancy (CSP) with expectant management. Methods Eleven patients with CSP who were diagnosed in the first trimester in the Third Affiliated Hospital of Guangzhou Medical University from January 2015 to March 2017 were recruited. All of them received expectant management. Nine pregnancies continued to the third trimester (the third trimester group), and 2 patients were expected to the second trimester (the second trimester group). The gestational age at diagnosis, CSP type, gravidity, parity, miscarriage and previous cesarean section history, gestational weeks at termination, amount of postpartum hemorrhage, prenatal and postnatal hemoglobin levels, pregnancy outcomes and obstetric complications were compared between the two groups. Results The third trimester group terminated pregnancies between 33 + 2 and 36 + 5 weeks. The second trimester group terminated in the second trimester because of rupture of uterus (at 17+2,17+3 weeks). There was no statistical difference between the two groups regarding the number of gravidity, parity and previous cesarean section(all P>0.05). The number of miscarriage in the second trimester group was 4.0 ± 2.8,and in the third trimester group was 1.3 ± 1.1(P<0.05). In the third trimester group, 7 cases were CSP typeⅠand 2 cases were CSPⅡ. In the second trimester group, 2 cases were both CSP typeⅢ. Eleven cases were diagnosed placenta accreta pathologically. There was no maternal death,and 6 cases received hysterectomy (6/11). The amount of postpartum hemorrhage increased remarkably and all neonates survived (pregnancy terminated between 33+2 and 36+5 weeks). Conclusions For those diagnosed as CSP typeⅠandⅡwho urge to continue pregnancies, it′s plausible to have expectant management with fully consent of obstetric hemorrhage, rupture of uterus and hysterectomy and close monitoring in tertiary hospital. The detailed expectant management of CSP is needed further exploration.
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The measurement of portal vein pressure (PVP) is important for the evaluation of therapeutic efficacy and prognosis in patients with liver cirrhosis.Aims: To investigate a non-invasive method for evaluating PVP in model of liver cirrhosis in rats.Methods: Liver cirrhosis model in rats was induced by intraperitoneal injection with thioacetamide.Magnetic resonance imaging with TOF sequence was used to measure portal vein diameter (PVD).PVP was detected directly by transvenous catheterization of portal vein.Body weight, liver weight, spleen weight, liver volume and spleen volume were determined.The hydroxyproline content in liver was determined by alkaline hydrolysis assay, proportion of collagen area in liver was detected by Sirius red staining.Results: Liver cirrhosis model in rats was successfully established after intraperitoneal injection for 20 weeks.Compared with control group, mean PVP, liver weight, liver volume, spleen weight, PVD, liver volume/body weight (LV/BW) ratio, spleen volume/body weight (SV/BW) ratio, hydroxyproline content and proportion of collagen area were significantly increased in model group (P<0.05), and body weight was significantly decreased (P<0.001).PVP was positively correlated with LV/BW ratio and proportion of collagen area (P<0.05).Conclusions: LV/BW and proportion of collagen area can indirectly reflect the PVP, and may provide a non-invasive approach for evaluation of portal hypertension.
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<p><b>OBJECTIVE</b>To investigate the reversal effects of different concentrations of DNA methylation inhibitor, 5-aza-2-deoxycytidine, on the hypermethylation of maternally expressed gene 3 (MEG3) gene promoter, and then the inhibitory effect of restoration of MEG3 expression on the proliferation of ovarian cancer cells.</p><p><b>METHODS</b>Human ovarian cancer OVCAR3 cells were treated with various concentration of 5-aza-2-deoxycytidine (0, 1, 5, 10, 20 µmol/L, respectively) for 6 days. Then the methylation status of MEG3 promoter was detected by methylation specific PCR (MSP). The alteration of MEG3 gene expression was detected by RT-PCR. Cell proliferation was determined by MTT assay and EdU incorporation assay.</p><p><b>RESULTS</b>After treated with 5-aza-2-deoxycytidine, the methylation status of MEG3 in the 0, 1, 5, 10, 20 µmol/L 5-aza-2-deoxycytidine groups were 1.00 ± 0.00, 0.79 ± 0.00, 0.67 ± 0.00, 0.65 ± 0.03 and 0.61 ± 0.01 folds, respectively (P < 0.05 for all). The relative expressions of MEG3 mRNA in the 0, 1, 5, 10, 20 µmol/L 5-aza-2-deoxycytidine groups were 1.00 ± 0.00, 2.04 ± 0.16, 2.44 ± 0.17, 3.19 ± 0.34 and 5.34 ± 0.39, respectively (P < 0.05 for all). In contrast to the negative control, the inhibition rates of the OVCAR3 cell growth were increased significantly when treated with 1, 5, 10, 20 µmol/L 5-aza-2-deoxycytidine in 2, 4 and 6 days. There were (40.78 ± 0.80)%, (35.65 ± 0.33)%, (31.81 ± 0.66)%, (27.33 ± 1.27)% and (17.75 ± 1.85)% of EdU-positive cells in the 0, 1, 5, 10 and 20 µmol/L 5-aza-2-deoxycytidine groups (P < 0.01 for all).</p><p><b>CONCLUSIONS</b>Maternally expressed gene 3 promoter hypermethylation is reversed by 5-aza-2-deoxycytidine in ovarian cancer cells. The downregulation of MEG3 gene might be resulted from the methylation, and the re-expression of MEG3 partly contribute to the growth inhibition of epithelial ovarian cancer cells.</p>
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Female , Humans , Antimetabolites, Antineoplastic , Pharmacology , Azacitidine , Pharmacology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Neoplasms, Glandular and Epithelial , Ovarian Neoplasms , Promoter Regions, Genetic , RNA, MessengerABSTRACT
Objective To explore the role of default mode network (DMN) in the pathophysiology of depression and the correlations between the functional connectivity (FC) of DMN and the clinical characteristics of depression through the resting-state fMRI scan in depressed patients. Methods Sixteen medication-na?ve patients with major depressive disorder and 15 healthy controls were recruited and underwent the resting-state MRI scan. Hamiliton depression rating scale (HAMD) was used to evaluate patients’symptom. The FC of DMN and its correlations with clinical features of pa-tients were analyzed. Results Compared with healthy controls, the FC within DMN in depressed patients is disturbed. There were negative correlations between the left mPFC-left hippocampus FC and HAMD total scores (r=-0.569, P=0.021) and subscale scores for sluggishness (r=-0.498, P=0.050). The left mPFC-right hippocampus FC in patients was negatively correlated with HAMD scores (r=-0.508, P=0.045). There were negative correlations between FC in the hippo-campus and HAMD subscale scores for cognitive impairment (r=-0.509, P=0.044). Conclusions The results suggest that there is abnormal FC within DMN in drug-na?ve patients with depression during resting state and some abnormal altera-tions of FC may be correlated with the clinical characteristics in depression.
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Objective To study the relationship between the methylation status of CPG islands in MEG3 gene promoter region of epithelial ovarian cancer and its clinical and pathological features. Methods The promoter methylation status was evaluated by MSP (methylation-specific polymerase chain reaction ) in 47 cases of ovarian cancer tissue and 15 cases of normal control. Results The methylation ratio (42.6%) of the MEG3 genes in the ovarian cancer was statistically significantly higher (P = 0.035 ) than that (13.3%) in the normal control. The methyation rate of the group with an age > 60 years old was slightly higher than that of the group with an age≤60 years old, without statistically significant (P > 0.05), so was observed in ovarian cancers of stage Ⅰ andⅡ than that in stage Ⅲ and Ⅳ. There were also no significant differences in MEG3 gene methylation positive rate neither in different pathological grading nor in various ovarian cancer tissues (P > 0.05). Conclusion Abnormal methylation in MEG3 gene may be associated with epithelial ovarian cancer , but no relation to its clinical pathology.
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To explore novel non-opioid analgesic agents, 16 compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. YX0611-1 was treated as the leading compound. The results of mice writhing model and hot plate model showed that compounds 2, 7, 8, 9, 11 and 15 had obvious analgesic activities in vivo. The test of affinity to mu, delta, kappa receptor displayed that active compounds didn't act on opioid receptor. The results of preliminary toxicity and pharmacokinetic tests showed that compound 7 had better safety and pharmacokinetic properties than that of YX0611-1, and it deserved further development.
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Compounds with serotonin reuptake inhibition/5-HT(1A) dual activity were used to build 3D pharmacophore model as a training molecules by Discover Studio. Based on the model, 8 novel aryl piperazine benzo[b][1,4] oxazine derivatives were designed and synthesized, and their structures were confirmed by 1H NMR and HR-MS. Biological evaluation illustrated that compounds VI(1) and VI(7) showed potent functional activities at both 5-HT transporter and 5-HT(1A) receptor, which can be used as lead compounds to guide future research of design and synthesis of potent novel compounds.
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Objective To construct pEGFP-C1-HSP27 recombinant eukaryotic expression vector and establish human pancreatic cancer SW1990 cell line stably expressing HSP27.Methods RT-PCR was applied to amplify human HSP27 cDNA from human pancreatic cancer SW1990 cells with a pair of specific primers carrying a restriction enzyme site BamH Ⅰ or Hind Ⅲ on each 5' end.HSP27 cDNA was inserted into pEGFP-C1 vector and then identified by restriction enzyme digestion and sequencing.Successful constructed pEGFP-C1-HSP27 or empty vector was transfected into SW1990 cells by lipofectamine 2000,respectively.The location of HSP72 was determined by fluoroscopy,RT-PCR and Western blot was used to detect the expression of HSP27 in transfected cell.Results The DNA sequence of pEGFP-C1-HSP27 recombinant plasmid was completely correct,and it was successfully transfected into SW1990 cell lines and stably transfected SW1990 cell lines were obtained,which were confirmed by restriction enzyme and sequencing.The expression of EGFP was distributed in cytoplasm,the HSP27mRNA expression was significantly increased (1.458 ± 0.160vs0.897 ±0.051,P ＜0.05).In addition,it was showed that EGFP-HSP27 fusion protein was expressed.Conclusions The eukaryotic expression vector pEGFP-C1-HSP27 was constructed successfully and stably transfected SW1990 cell line expressing HSP27 was obtained.
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Objective To investigate the brain metabolic changes and evaluate their spatial distributions after traumatic axonal injury (TAI)in rats by using proton magnetic resonance spectroscopy(1H-MRS).Methods The TAI model was made by subjecting the head of the rats to the linear and angular accelerations.The multi-voxel MRS was employed to detect the tissue metabolic state at the levels of hippocampus-caudate and pons prior to injury and at 24 hours after injury.The alterations of NAA/Cr,NAA/Cho and Cho/Cr values as well as the spatial distribution of NAA/Cr reduction were accessed. Immunohistochemical staining for β-APP was used to observe the injured axons. Results A siguificantdecrease in NAA/Cr and NAA/Cho(P<0.05)and subtle increase in Cho/Cr(P>0.05)were observed in rats at 24 hours after TAI in comparison to the pre-injury levels.Notable decrease in NAA/Cr value was observed in the areas including the brain stem,hippocampus,internal capsule,corpus callosum and thalamus,where axonal injuries were confirmed by the histological examination. Conclusion Metabolic imbalances Occur in the brains of rats with TAI.with notable changes in the brain stem and the hippocampus.
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Objective To assess differences in brain activation between active and passive movement of the right hand using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). Methods Nine healthy adult right handed volunteers were studied. fMRI was performed with active and passive finger-to-finger movement. Results Right hand active and passive movement produced significant activation in the contralateral sensorimotor cortex ( SMC ), the contralateral premotor cortex ( PMC ), bilaterally in the supplementary motor area (SMA) and in the ipsilateral cerebellum. The activated brain areas were centered on the contralateral SMC and PMC and located more forward during active movement than during passive movement. The contralateral SMC was the most strongly and the most frequently activated brain area. The contralateral posterior parietal cortex (PPC) was less relevant to the hand movements. Unlike active movement, passivemovement activated more areas in the posterior central gyrus than in the anterior central gyrus. Conclusions Both active and passive movement significantly activate the brain areas which are responsible for hand movement, but there are some differences in the locations of the cortex areas activated and in the incidence activation except in the contralateral SMC.
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To explore novel monoamine reuptake inhibitor with antidepressant activity, a series of substituted aryl alkanol piperidine derivatives were designed and synthesized. All of them were new compounds, and their structures were confirmed with 1H NMR and HR-MS. The results showed that compounds 4, 5 and 8 displayed strong 5-HT, NA and DA reuptake inhibiting activities in vitro. Among the tested compounds, 4, 5 and 13 exhibited potent antidepressant activities in the mice forced swimming test. Compounds 4 and 5 have potent antidepressant activities and are worth further development.
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Data analysis poses a significant challenge to the large-scale proteomics studies. Based on the structured and controlled vocabularies-Gene Ontology (GO), and the GO annotation from related databases, a strategy composed of several programs and local databases is developed to identify the functional distribution and the significantly enriched functional categories of the proteomic expression profile. It would be helpful for understanding the overall functions of these identified proteins and supply the fundamental information for further bioinformatics exploration. This strategy has been successfully used in the Human Fetal Liver (HFL) proteomic research, which is available online at http://www.hupo.org.cn/GOfact/.