A clinical scoring model based on Gd-EOB-DTPA enhanced MRI predicting microvascular invasion in hepatocellular carcinoma: a multicenter study / 中华放射学杂志

Objective:To establish a clinical diagnostic scoring model for preoperative predicting hepatocellular carcinoma (HCC) microvascular invasion (MVI) based on gadolinium-ethoxybenzyl-diethylenetriamine pentacetic acid (Gd-EOB-DTPA) enhanced MRI, and verify its effectiveness.Methods:From January 2014 to December 2020, a total of 251 cases with pathologically confirmed HCC from Tianjin First Central Hospital and Jilin University First Hospital were retrospectively collected to serve as the training set, while 57 HCC patients from Tianjin Medical University Cancer Hospital were recruited as an independent external validation set. The HCC patients were divided into MVI positive and MVI negative groups according to the pathological results. The tumor maximum diameters and apparent diffusion coefficient (ADC) values were measured. On the Gd-EOB-DTPA MRI images, tumor morphology, peritumoral enhancement, peritumoral low intensity (PTLI), capsule, intratumoral artery, intratumoral fat, intratumoral hemorrhage, and intratumoral necrosis were observed. Univariate analysis was performed using the χ 2 test or the independent sample t-test. The independent risk factors associated with MVI were obtained in the training set using a multivariate logistic analysis. Points were assigned to each factor according to the weight value to establish a preoperative score model for predicting MVI. The receiver operating characteristic (ROC) curve was used to determine the score threshold and to verify the efficacy of this scoring model in predicting MVI in the independent external validation set. Results:The training set obtained 98 patients in the MVI positive group and 153 patients in the MVI negative group, while the external validation set obtained 16 patients in the MVI positive group and 41 patients in the MVI negative group. According to logistic analysis, tumor maximum diameter>3.66 cm (OR 3.654, 95%CI 1.902-7.018), hepatobiliary PTLI (OR 9.235, 95%CI 4.833-16.896) and incomplete capsule (OR 6.266, 95%CI 1.993-9.345) were independent risk factors for MVI in HCC, which were assigned scores of 3, 4 and 2, respectively. The total score ranged from 0 to 9. In the external validation set, ROC curve analysis showed that the area under the curve of the scoring model was 0.918 (95%CI 0.815-0.974, P=0.001). When the score>4 was used as the threshold, the accuracy, sensitivity, and specificity of the model in predicting MVI were 84.2%, 81.3%, and 85.4%, respectively. Conclusions:A scoring model based on Gd-EOB-DTPA-enhanced MRI provided a convenient and reliable way to predict MVI preoperatively.

New tale on LianHuaQingWen: IL6R/IL6/IL6ST complex is a potential target for COVID-19 treatment.

LianHuaQingWen (LHQW) improves clinical symptoms and alleviates the severity of COVID-19, but the mechanism is unclear. This study aimed to investigate the potential molecular targets and mechanisms of LHQW in treating COVID-19 using a network pharmacology-based approach and molecular docking analysis. The main active ingredients, therapeutic targets of LHQW, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt, STRING, and GeneCards databases. According to the "Drug-Ingredients-Targets-Disease" network, Interleukin 6 (IL6) was identified as the core target, and quercetin, luteolin, and wogonin as the active ingredients of LHQW associated with IL6. The response to lipopolysaccharide was the most significant biological process identified by gene ontology enrichment analysis, and AGE-RAGE signaling pathway activation was prominent based on the interaction between LHQW and COVID-19. Protein-protein docking analysis showed that IL6 receptor (IL6R)/IL6/IL6 receptor subunit beta (IL6ST) and Spike protein were mainly bound via conventional hydrogen bonds. Furthermore, protein-small molecule docking showed that all three active ingredients could bind stably in the binding model of IL6R/IL6 and IL6ST. Our findings suggest that LHQW may inhibit the lipopolysaccharide-mediated inflammatory response and regulate the AGE-RAGE signaling pathway through IL6. In addition, the N-terminal domain of the S protein of COVID-19 has a good binding activity to IL6ST, and quercetin and wogonin in LHQW may affect IL6ST-mediated IL6 signal transduction and a large number of signaling pathways downstream to other cytokines by directly affecting protein-protein interaction. These findings suggest the potential molecular mechanism by which LHQW inhibits COVID-19 through the regulation of IL6R/IL6/IL6ST.

Roles and Clinical Significances of ATF6, EMC6, and APAF1 in Prognosis of Pancreatic Cancer.

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to evaluate prognosis value of ATF6, EMC6, XBP1, CHOP, and APAF1 in PC. Clinical data from 69 PC patients were retrospectively analyzed. Immunohistochemistry, Western blotting, and qRT-PCR were used for the assessment of gene or protein expression. The cell counting kit-8 (CCK-8) and the Transwell invasion assays were, respectively, used for the assessment of the proliferative and invasive abilities of PC cells. The prognostic values of ATF6, XBP1, CHOP, EMC6, and APAF1 in PC patients were evaluated using Kaplan-Meier and Cox regression analyses. Results: XBP1 and CHOP expressions were not associated with PC recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). ATF6 upregulation and EMC6 and APAF1 downregulations significantly correlated with the poor RFS, OS, and DSS of PC patients. ATF6 promoted PC cell proliferation and invasion, while EMC6 and APAF1 inhibited these events. Conclusion: ATF6 upregulation and EMC6 and APAF1 downregulations may be valid indicators of poor prognosis of PC patients. Moreover, ATF6, EMC6, and APAF1 may constitute potential therapeutic targets in PC patients.

Parecoxib Improves the Outcomes of Acute Mild and Moderate Pancreatitis: A 3-Year Matched Cohort Study Based on a Prospective Database.

OBJECTIVES: The aim of this study was to evaluate the role of parecoxib in patients with different severities of acute pancreatitis (AP). METHODS: A total of 772 eligible patients with AP were divided into 4 groups: mild and moderately AP (MAP) treated with parecoxib (group A, n = 236), MAP without parecoxib treatment (group B, n = 453), severe AP (SAP) treated with parecoxib (group C, n = 28), and SAP without parecoxib treatment (group D, n = 55). Patients in group A were exactly matched with patients in group B by propensity score matching, similar to the matching between group C and group D. RESULTS: The morbidity of abdominal infection in group A was significantly lower as compared with that in group B (P < 0.050). The progression of MAP to SAP significantly decreased in group A than group B (P < 0.050). No significant differences were observed between group C and group D. The risk factors independently related to the progression of MAP included alcoholic/high-fat dietary (P = 0.028) and parecoxib administration (P = 0.011). CONCLUSIONS: Early administration of parecoxib could reduce the morbidity of complications among patients with MAP. Parecoxib may prevent the progression of MAP to SAP and improve its outcomes.

Role of TGFß3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of tumour-associated mortality worldwide, but no significant improvement in treating HCC has been reported with currently available systemic therapies. Immunotherapy represents a new frontier in tumour therapy. Therefore, the immunobiology of hepatocarcinoma has been under intensive investigation. Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, is an immune suppressor associated with tumourigenesis and cancer metastasis. However, little is known about the role of DcR3 in the immunobiology of hepatocarcinoma. In this study, we found that overexpression of DcR3 in HCC is mediated by the TGFß3-Smad-Sp1 signalling pathway, which directly targets DcR3 promoter regions. Moreover, overexpression of DcR3 in HCC tissues is associated with tumour invasion and metastasis and significantly promotes the differentiation and secretion of Th2 and Treg cells while inhibiting the differentiation and secretion of Th1 cells. Conversely, knockdown of DcR3 expression in HCC significantly restored the immunity of CD4+ T cells. Inhibition of DcR3 expression may provide a novel immunotherapeutic approach to restoring immunity in HCC patients.

BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells / 中国药理学与毒理学杂志

mTOR is commonly activated in human cancer and an attractive therapeutic target.Its activation is caused primarily by oncogenic mutations in RAS/RAF/MAPK and PI3K/AKT pathways, which cooperate to promote cancer progression and therapeutic resistance. mTOR inhibitors induce growth suppression and death receptor/FADD-dependent apoptosis in colon cancer cells and xeno-grafts. Using a panel of BRAFV600E and WT colorectal cancer cell lines and in vitro selected resistant culture, and xenograft models, we demonstrate here that BRAFV600E confers resistance to mTOR inhibitors. Everolimus treatment disrupts the S6K1-IRS-2/PI3K negative feedback loop, leading to BRAFV600E-dependent activation of ERK and Mcl-1 stabilization in colon cancer cells, which in turn blocks the crosstalk from the death receptor to mitochondria. Co-treatment with inhibitors to Mcl-1, PI3K, RAF or MEK restores mTOR inhibitor-induced apoptosis by antagonizing Mcl-1 or abrogating pERK/Mcl-1 elevation in BRAFV600E cells. Our findings provide a rationale for genotype-guided patient stratification and potential drug combinations to prevent or mitigate undesired activation of survival pathways induced by mTOR inhibitors.

Explicit physical self and its correlation with their implicit physical self in college students / 中国心理卫生杂志

Objective:To investigate the relationship between explicit and implicit physical self among contemporary college students.Methods:A total of 485 college students were recruited,with 264 male students,221 female students,266 junior students,219 senior students,189 students in the urban areas and 296 students in the rural areas.The Adolescents'Physical Self Scale (APS) was used to measure their explicit physical self.The Implicit Association Tests were designed to examine implicit physical self of 50 college students,who were selected from 485 college students by isometric random sampling.Results:The difference were significant among the five dimensions of college students' APS scores (P ＜ 0.001).The average scores of college students' appearance,sexual attractiveness were the highest,while the average score of body flaws was the lowest.Male students scored higher in five APS dimensions than female students (Ps ＜ 0.05).Senior students scored higher in the appearance,movement characteristics,figure and body flaws than junior students (Ps ＜0.05).Students in the urban areas scored higher in the appearance,movement characteristics,figure and body flaws than the students in the rural areas(Ps ＜ 0.05).There was no significant correlation between explicit and implicit physical self (P ＞ 0.05).The scores of relative separation index of movement characteristics were lower in male students than in female students (Z =2.45,P ＜ 0.05).The scores of relative separation index of body flaws were lower in the urban ones than in the rural ones (Z =3.14,P ＜ 0.01).Conclusion:It suggests that separation phenomenon exists between explicit and implicit physical self and the separation phenomena is distinct among the students of different genders or from different areas.

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-ß3/SMAD signaling pathway in CRC.

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-ß3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-ß3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-ß3/SMAD-mediated EMT of CRC cells.

Statin use and risk of gallstone disease: A meta-analysis.

AIM: There is emerging evidence from animal and human studies that current statins can decrease the formation of gallbladder cholesterol gallstones and subsequently decrease the risk of gallstone disease, but consistent results have not been reported. We performed a meta-analysis to provide an overview of the relevant studies. METHODS: Relevant studies published between January 1980 and February 2014 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between statin use and risk of gallstone disease was assessed by adjusted odds ratio (OR). RESULTS: A total of 622 868 participants from six studies (four case-control studies, one cohort study and one cross-sectional study) were identified in this meta-analysis. The studies provided adjusted overall OR estimates for current statin use versus non-use, leading to a pooled OR of 0.86 (95% confidence interval [CI], 0.77-0.97; P < 0.001). The overall OR of population-based case-control studies and cholecystectomy due to gallstone disease were 0.83 (95% CI, 0.73-0.95; P = 0.0131) and 0.78 (95% CI, 0.74-0.82; P = 0.615), respectively. CONCLUSION: There is evidence that current statin use lowers the risk of gallstone disease compared with non-use, especially for cholecystectomy due to gallstone disease. Low statin use (1-4 prescriptions) did not decrease the risk of gallstone disease, but moderate and high statin use significantly decreased the risk. Further multicenter and better controlled studies are needed to confirm these findings.

Discussing of Mental Rehabilitation of Children with Disability under ICF Theory and Practice / 中国康复理论与实践

@#Objective To discuss the mental rehabilitation of disabled children under International Classification of Functioning, Disabil-ity and Health (ICF). Methods The target, the organization of work team, environment support and the core problems of disabled children's mental rehabilitation were discussed based on the concept of ICF. Results The goal of mental rehabilitation was to recover the mental func-tion of disabled children. The multidisciplinary team should include medicine, psychology, education, social work and so on. Supportive en-vironments such as professional workers, families, communities, partner and barrier-free environment were the effective means of disabled children's mental rehabilitation. Respect and equality were the precondition of disabled children's mental rehabilitation, and positive atten-tion should be the working attitude. Conclusion ICF-CY can provide a new perspective and framework for the mental rehabilitation of dis-abled children.

A highly selective ratiometric visual and red-emitting fluorescent dual-channel probe for imaging fluoride anions in living cells.

Recently, growing attention has been paid to the accurate determination of fluoride anion (F(-)) in the environment and living systems for its toxicity and biological function investigation. In this paper, we developed a ratiometric visual and red-emitting fluorescent dual-channel probe (1) employed Si-O bond as a highly selective recognition receptor for imaging F(-) in living cells. Probe 1 possesses a potential internal charge transfer (ICT) structure, and displays a large (158 nm) red-shifted absorption spectrum and the color changes from yellow to blue upon addition of F(-) in the aqueous solution. In addition, probe 1 can be used to detect F(-) quantitatively by the ratiometric absorption and turn-on fluorescence spectroscopy methods with excellent sensitivity. Finally, the results of its application to bioimaging of F(-) in living cells show that probe 1 would be of great benefit to biomedical researchers for investigating the effects of fluoride in biological systems.

Null genotypes of GSTM1 and GSTT1 contribute to male factor infertility risk: a meta-analysis.

OBJECTIVE: To study the null of GSTM1, GSTT1, or GSTT1-GSTM1 and the risk of male factor infertility. DESIGN: Meta-analysis using electronic databases (Pubmed, Medline, Embase, and China National Knowledge Infrastructure) up to August 22, 2011. SETTING: The strength of the relationship between the null of GSTM1, GSTT1, and GSTT1-GSTM1 and the risk of male factor infertility was assessed by odds ratios (ORs). A total of 16 studies were identified in this meta-analysis. Among the 16 studies, 15 studies reported GSTM1null, 10 reported GSTT1, and five reported GSTM1-GSTT1. PATIENT(S): Male infertility patients and a fertile control group. INTERVENTION(S): Meta-analyses by means of random-effects models and fixed-effects models. MAIN OUTCOME MEASURE(S): Ratio of male factor infertility. RESULT(S): The studies provided overall OR estimates for GSTM1, GSTT1, and GSTM1-GSTT1, leading to a pooled OR of 1.41 (95% confidence interval [CI], 1.10-1.81), 1.15 (95% CI, 0.95-1.39), and 2.99 (95% CI, 2.14-4.18), respectively. CONCLUSION(S): There was evidence that the null of GSTM1 and GSTM1-GSTM1 increased the risk of male factor infertility, but the null genotype of GSTT1 was not associated with an increased infertility risk. We still need further multicenter and better controlled studies to confirm these findings.

A highly selective colorimetric chemodosimeter for fast and quantitative detection of hydrogen sulfide.

Based on the fact that hydrogen sulfide (H(2)S) possesses the smallest steric hindrance among thiols and the SH(-) group adds faster to an electron-poor C=C double bond, we designed and synthesized a tricyanoethylene-derived colorimetric chemodosimeter 1 for the fast and highly selective assay of H(2)S. Chemodosimeter 1 exhibited excellent water-solubility due to the introduction of two hydrophilic hydroxyl groups. Upon the addition of Na(2)S, chemodosimeter 1 showed a fast (complete within 400 s) and robust decrease of the absorption intensity (>97%), accompanied by a color change from red to colorless. Additionally, a linear relationship between absorption intensity and the added Na(2)S concentrations (0-130 µM) was observed in aqueous buffer solution (pH 7.4, 20 mM PBS). Importantly, the proposed paradigm in this paper, adoption of the tricyanoethylene derivative as a recognition receptor to distinguish H(2)S from other thiols and analytes, provides a promising methodology for the design of colorimetric and fluorescent chemodosimeters for fast determination of H(2)S.

Implications of World Report on Disability to Services of Rehabilitation for Persons with Disabilities in China / 中国康复理论与实践

@#World Report on Disability discussed the current situation of persons with disabilities, health care, rehabilitation, support and assistance, barrier-free environment, education, employment, and relevant policy recommendations, adhering to the spirit of Convention on the Rights of Persons with Disabilities, using the International Classification of Functioning, Disability and Health as its theoretical structure.Based on the report, this article discussed the revelations to services of rehabilitation for persons with disabilities and their problems,which were advocating new concepts of rehabilitation services, using multidisciplinary rehabilitation model, and strengthening construction of talents in services of rehabilitation.

[Adult-to-adult living-related donor liver transplantation: report of 2 cases].

OBJECTIVE: To investigate the feasibility and safety of adult-to-adult living-related donor liver transplantation using a right lobe graft. METHODS: The clinical data of 2 cases of living-related donor liver transplantation performed between July, 2010 and November, 2010 were analyzed. RESULTS: Liver transplantation was performed using a right lobe graft including the middle hepatic vein in one case and a right lobe graft without the middle hepatic vein in the other. The ratio of graft volume to standard liver volume was 46.2% and 47.3% in the two cases, with GR/WR of 0.83 and 0.80, and donor residue liver of 42.1% and 39.5%, respectively. The donor operation lasted for 6.5 h and 5 h in the two cases with blood loss of about 200-250 ml without blood transfusion. The donors recovered uneventfully without any surgical complications, whose liver function was normal 7 days after the operation, and were discharged 14 days and 16 days after the surgery, respectively. The recipient operation lasted for 8 h and 7 h with blood loss of about 800-1000 ml. The right hepatic vein, hepatic artery, portal vein and bile duct reconstruction were performed by end-to-end anastomoses in the 2 recipients. Bile duct anastomosis stricture occurred in the first recipient 2 months after transplantation and was treated with percutaneous transhepatic cholangiography and drainage. The second recipient recovered smoothly without any complications. The recipients have so far survived 9 months and 5 months, respectively. CONCLUSION: Adult-to-adult living-related donor liver transplantation is a safe and effective option for treatment of end-stage liver diseases in the context of cadaveric liver graft shortage.

Meta-analysis of alcohol consumption and risk of extrahepatic bile system cancer.

AIM: Alcohol consumption increases the risk of liver cancer. However, there is still controversy regarding alcohol consumption and the risk of extrahepatic bile system cancer (EBSC). We performed a meta-analysis to provide an overview of the relevant studies and gain more robust estimates of the relationship between alcohol consumption and risk of EBSC. METHODS: Relevant studies published between January 1966 and October 2010 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between alcohol consumption and risk of EBSC was assessed by adjusted odds ratio (OR). RESULTS: A total of 113 767 participants from 10 studies (nine case-control studies and one cohort study) were identified in this meta-analysis. The studies provided adjusted overall OR estimates for drinkers versus non-/low drinkers, leading to a pooled adjusted OR of 0.82 (95% confidence interval [CI] = 0.72-0.94, P for heterogeneity = 0.194, I(2) = 27.2%). The overall adjusted OR of hospital-based studies and population-based studies were 0.80 (95% CI = 0.65-0.99, P = 0.260) and 0.79 (95% CI = 0.64-0.98, P = 0.119), respectively. For the heavy drinkers, the adjusted OR significance increased to 1.58 (95% CI = 0.97-2.57, P for heterogeneity = 0.055, I(2) = 65.4%), but it had no statistical significance. CONCLUSION: There is evidence that moderate alcohol consumption lowers the risk of EBSC compared with non-/low alcohol consumption, but not heavy alcohol consumption. Further multicenter and better controlled studies are required to confirm these findings.

Proportion of CD34(+)CD38(-) cell population in bone marrow of patients with de novo AML as prognostic factor of complete remission at first course of induction chemotherapy / 中国实验血液学杂志

This study was to investigate the relationship between the CD34(+)CD38(-) cell population and its proportion in G(0) phase of de novo AML non-M(3) at diagnosis and the clinical and experimental characteristics. The flow cytometry was used to detect the expression of the cell surface antigen CD34 and CD38 in the bone marrow mononuclear cells (MNC) of the AML non-M(3) at diagnosis and investigate the cell cycle of the subpopulations, and then the relationships between the proportion of CD34(+)CD38(-)cell population and its G(0) state and the complete remission (CR) rate after the first induction chemotherapy was analyzed. The results showed that the proportion of the CD34(+)CD38(-) cell population and its G(0) phase had no relationship with the karyotypes and WBC count at new diagnosis and the Flt3/ITD status, but correlate with the blasts in the bone marrow after the first course induction chemotherapy. The proportion of the CD34(+)CD38(-) cells in patients who have visible blasts in the bone marrow at day 7 after completion of the first course induction chemotherapy was (12.47 ± 26.26)%, but the counterparts was (2.62 ± 7.20)% in the group of patients whose bone marrow had no visible blasts (p = 0.031). The proportion of the CD34(+) cell population in patients who had visible blasts in the bone marrow at day 1 after completion of the first course induction chemotherapy was (17.40 ± 21.20)%, yet the proportion of the CD34(+) cell populations was (5.64 ± 6.96)% in the patients who had no visible blasts in the bone marrow (p = 0.001). The proportion of the CD34(+)CD38(-) cell populations in the patients who achieved CR after the first course induction chemotherapy was (2.51 ± 9.72)%, which was lower than the proportion (24.92 ± 27.04%) of the non-CR patients (p = 0.001). Furthermore, the proportion (1.60 ± 4.82%) of the CD34(+)CD38(-) cell population in the AML non-M(2b) CR patients was more obviously lower than that in the non-CR patients (p < 0.001). In univariate analysis, whether or not achieved CR after the first course induction chemotherapy correlated with age (p = 0.022), the proportion of the CD34(+)CD38(-) cell population (p = 0.008) and the proportion of the visible blasts in the bone marrow at day 7 after induction therapy (p = 0.011). Multivariate analysis showed that only the proportion of the CD34(+)CD38(-) cells had correlation tendency with CR rate. It is concluded that the proportion of the CD34(+)CD38(-) cells in bone marrow of de novo AML non-M(3) is a prognostic factor to anticipate the CR rate of the first course for induction therapy.

Resistance of leukemia KG1a cells with positive N-cadherin in phase G(0) against killing activity of VP16 / 中国实验血液学杂志

Drug resistance is an important character of leukemic stem cells. To explore the mechanism of the chemotherapy resistance of N-cadherin positive leukemia cells, the quiescent state of N-cadherin positive leukemia cells was determined by flow cytometry and the relationship of G(0) phase cell ratio with the chemotherapy resistance was analyzed. After KG1a cells were induced to enter cell cycle, the G(0) phase cell ratio and the sensitivity of cells to VP16 were determined. Finally the quiescent state and drug resistance properties of KG1a cells were determined after inhibiting N-cadherin-mediated cell-cell interaction by EGTA treatment. The results showed that the G(0) phase cell ratio in N-cadherin positive KG1a cells was higher than that in N-cadherin negative KG1a cells. After KG1a cells were induced to enter cell cycle, the G(0) phase cell ratio was decreased significantly and the sensitivity of KG1a cells to VP16 increased. Following EGTA treatment for 24 hours, the G(0) phase cell ratio decreased and the drug-sensitivity was enhanced significantly. It is concluded that N-cadherin-mediated adhesion keeps N-cadherin positive leukemia cells in quiescent state of G(0) phase, thus protect these leukemia cells against VP16 chemotherapy.

[Therapeutic efficacy of Nexavar on liver cancer and its relation to the expression of Ki-67 and CD34].

OBJECTIVE: To study the therapeutic effects of Nexavar on liver cancer and its relation to the expressions of Ki-67 and CD34. METHODS: Twenty-eight patients with liver cancer were treated with Nexavar. The therapeutic efficacy of Nexavar on liver cancer was observed. Liver cancer tissues were examined for the expressions of Ki-67 and CD34 by immunohistochemistry. Microvessel density (MVD) was calculated according to the expression of CD34. RESULTS: Of 28 patients, none achieved a complete response (CR), 12 had a partial response (PR), 7 had stable disease (SD), and 9 progressive disease (PD). The efficacy of Nexavar was associated significantly with Ki-67 expression. The mean MVD count was 346.03-/+146.98 in PR patients, and 89.14-/+45.66 in PD patients. There was a significant difference in MVD between PR and PD patients. CONCLUSION: There is a better efficacy of Nexavar in treatment of liver cancer in the patients who had Ki-67-positive expression and high MVD count.

[Hepatocyte apoptosis and expression of apoptosis-regulating genes during cold preservation and reperfusion injury in rat donor liver].

OBJECTIVE: To investigate the apoptosis of hepatocytes and the expression of apoptosis-regulating genes during the donor liver ischemia and reperfusion injury in rat orthotopic liver transplantation (OLT). METHODS: Seventy-two male SD rats were randomly divided into sham operation group and transplantation group. Using Ringer's lactate solution as the perfusing and preserving solution, the grafts were preserved for 4 h before orthotopic transplantation. At 1, 6 and 24 h after the reperfusion, the recipients were sacrificed, and the serum ALT and AST levels were measured; the changes of hepatocyte apoptosis was detected by TUNEL assay, and the protein expressions of the apoptosis-regulating genes were measured by flow cytometry. RESULTS: Serum ALT and AST levels were significantly higher in transplantation group than in the control group after reperfusion. In comparison with the control group, the rats in the transplantation group showed significantly increased apoptosis index in the livers, lowered Bcl-2 levels and increased FasL levels after the transplantation, especially at 6 h after liver reperfusion (P<0.01). CONCLUSION: The donor liver ischemia and reperfusion injury can promote hepatocyte apoptosis, which may be related with the high expression of Bcl-2 gene and low expression of FasL after reperfusion injury in rats with orthotopic liver transplantation.