Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Study of relationship between the blood supply of the extrahepatic bile duct and duct supply branches from gastroduodenal artery on imaging and anatomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Liver transplantation has become the treatment of choice for patients with end-stage acute or chronic hepatic disease. Bile duct complications are common events after liver transplantation. The aim of this study was to evaluate the blood supply of the human bile duct and identify the underlying mechanisms of bile duct complications after liver transplantation.</p><p><b>METHODS</b>The duct supply branches from gastroduodenal artery and blood supply of extrahepatic bile duct system were re-evaluated through selective hepatic angiography from 600 patients. In addition, 33 cadavers were injected with latex casting material into the common hepatic artery, then the extrahepatic bile duct and the branches from the common hepatic artery were carefully dissected to visualize the gastroduodenal artery and its branching to the extrahepatic bile duct.</p><p><b>RESULTS</b>The bile duct artery arose from the branch of the gastroduodenal artery in 8.1% (49/600). Of these 49 individuals, the bile duct artery was supplied by the gastroduodenal artery (61.22%, 30/49), the proper hepatic artery (14.29%, 7/49), or both the gastroduodenal artery and the proper hepatic artery (24.49%, 12/49). In our study of 33 cadavers, the percentage that the bile duct artery arose from the gastroduodenal artery was 27.27%. The blood supply to the bile extrahepatic bile ducts was divided into different segments and formed longitudinal and arterial network anastomosed on the walls of the duct.</p><p><b>CONCLUSIONS</b>There is a close relationship between the duct supply branches from gastroduodenal artery and the blood supplying patterns of the extrahepatic bile duct system. In liver transplant surgery, the initial part of the gastroduodenal artery is preferred to be preserved in the donor liver. It is of great significance to improve the success rate of operation and reduce complications.</p>

Effect of hepatitis B virus X protein on suppressor of cytokine signaling-1 expression / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of hepatitis B virus-encoded X protein (HBx) on the expression of host-encoded suppressor of cytokine signaling-1 (SOCS-1) and to explore the possibility of an underlying mechanism involving modulation of CpG island methylation in the SOCS-1 gene promoter.</p><p><b>METHODS</b>The immortalized human derived non-tumor liver cell line QSG7701 was transfected with a recombinant HBx plasmid (pcDNA-X) or an empty vector control plasmid (pcDNA3.0) and stably transfected clones were selected by G418 resistance screening. Untransfected cells served as negative controls. Expression of SOCS-1 mRNA and protein was detected by real-time quantitative PCR and western blotting. The methylation status of SOCS-1 was detected by methylation-specific PCR (MSP). The significance of intergroup differences was analyzed by one-way ANOVA or pairwise comparison with post-hoc LSD test.</p><p><b>RESULTS</b>SOCS-1 mRNA level was significantly lower in the pcDNA-X/QSG7701 cells compared to that in the pcDNA3.0/QSG7701 and untransfected cells (0.3249+/-0.0536 vs. 1.0543+/-0.1937 and 1.00; F = 19.6, P = 0.042). SOCS-1 protein level was similarly lower in the pcDNA-X/QSG7701 cells (0.1496+/-0.0106 vs. 0.1984+/-0.0438 and 0.2152+/-0.0816; F = 19.4, P = 0.048). The SOCS-1 promoter region showed methylation only in the pcDNA-X/QSG7701 cells.</p><p><b>CONCLUSION</b>HBx-expressing human hepatocytes have down-regulated SOCS-1 expression, both at the mRNA and protein levels, and this effect corresponds to increased methylation in the SOCS-1 promoter region harboring CpG islands.</p>

Effect of microRNA on proliferation caused by mutant HBx in human hepatocytes / 中华肝脏病杂志

To study the effect of micro (mi)RNA on cellular proliferation induced by hepatitis B x protein, HBx, in human liver cells and to investigate the underlying molecular mechanism of this cancer-related effect. The human L02 hepatocyte cell line was stably transfected with HBx (L02/HBx) or an HBx mutant (L02/HBx-d382) that induces higher levels of cellular proliferation. The differential miRNA expression profiles were determined by microarray analysis and confirmed by real-time PCR. Two miRNAs, miR-338-3p and miR-551b, that were found to be significantly down-regulated in the L02/HBx-d382 cells were selected for further study and transfected individually into cells using the lipofectamine procedure. The cell survival rate was analyzed by MTT assay, and cell cycles were assessed by flow cytometry. Expressions of cyclinD1, cyclinG1, and E2F1 were assessed by real-time PCR and Western blotting. Compared with the microarray miRNA profile of L02/pcDNA3.0 cells, six miRNAs were up-regulated and five miRNAs were down-regulated in the L02/HBx-d382 cells, while four miRNAs were up-regulated and 12 were down-regulated in the L02/HBx cells. The microarray results were consistent with real-time PCR results. Transfection of miR-338-3p and miR-551b significantly inhibited the cell survival rates (P less than 0.001) and induced G0/G1 phase cycle arrest. According to MTT results: for L02/HBx-d382 cells, compared with lipofectamine or non-transfected (NC) controls, the t value of miR-338-3p was 10.402, 9.133 and the t value of miR-551b was 8.763, 7.403; for L02/HBx cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 9.105, 8.074 and the t value of miR-551b was 7.673, 7.52. According to flow cytometry results: for L02/HBx-d382 cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 12.173, 11.107 and the t value of miR-551b was 15.364, 13.377; for L02/HBx cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 15.416, 13.378, and the t value of miR-551b was 13.276, 13.109. The protein levels of cyclinD1, cyclinG1, and E2F1 were significantly reduced by both miR-338-3p and miR-551b ( P less than 0.001). For L02/HBx-d382 cells, compared with lipofectamine or NC controls: E2F1 had t = 11.132, 10.031 and 12.017, 10.973, respectively; cyclinD1 had t = 15.654, 15.013 and 15.447, 14.733, respectively; cyclinG1 had t = 8.017, 7.661 and 7.402, 7.417, respectively. For L02/HBx cells, compared with lipofectamine or NC controls: E2F1 had t = 14.244, 13.331 and 15.022, 14.468, respectively; cyclinD1 had t = 8.695, 8.137 and 7.877, 7.503, respectively; cyclinG1 had t = 7.73, 7.471 and 7.596, 7.41, respectively. In contrast, the mRNA levels for E2F1, cyclinD1, and cylcinG1 showed no significant differences between the miRNA transfected cells and controls. Wild-type HBx and the high proliferation-inducing mutant HBx can influence the miRNA expression profile of L02 cells. HBx down-regulates miR-338-3p and miR-551b in L02 cells, and the high proliferation-inducing mutant has a more robust effect. The mechanism of miR-338-3p- or miR-551b-mediated cell growth inhibition appears to be related to the direct modulation of cyclinD1, cyclinG1, and E2F1.

Study on tumor formation of hepatocyte transformed by hepatitis B virus X gene in nude mice / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate whether hepatitis B virus X gene alone is sufficient to transform the non-transformed immortalized human liver cell line QSG7701 and induce hepatocellular carcinoma in vivo.</p><p><b>METHODS</b>pCMVX/QSG7701 cells were transplanted into subcutaneous tissue of nude mice. pRcCMV2/QSG7701 and QSG7701 cells were used as control. Tumor formation was checked within 5 weeks after transplantation. The activity and food intake of the nude mice were recorded. The texture, volume and metastasis of transplantation tumor were observed grossly, and the HE stained transplantation tumor tissues were observed under optical microscope.</p><p><b>RESULTS</b>The transplantation tumor occurred in all of the six nude mice inoculated with pCMVX/QSG7701 cells at the second week after inoculation. No metastatic tumor was found in other organs. Transplant tumor was not formed in all of the negative control groups. The activity, eating and drinking of the nude mice transplanted with pCMVX/QSG7701 cells were normal, while their weights were increased gradually in the first 3 weeks. Since the 4th week after transplantation with pCMVX/QSG7701 cells, the activity of the mice was decreased and their body weight was no longer increased. It is interesting that the mental state and eating of those nude mice inoculated with pRcCMV2/QSG7701and QSG7701 cells were normal, and the weight was increasing all the time after inoculation. HE staining analysis confirmed that the transplanted tumor was hepatocellular carcinoma.</p><p><b>CONCLUSION</b>HBx alone is sufficient to transform the non-transformed immortalized human liver cell line QSG7701 and induce hepatocellular carcinoma in vivo.</p>

Clinical observation on acupuncture for treatment of diabetic nephropathy / 中国针灸

<p><b>OBJECTIVE</b>To observe the clinical therapeutic effect of acupuncture on early metaphase diabetic nephropathy.</p><p><b>METHODS</b>Fifty-four cases of diabetes were randomly divided into an acupuncture group (n=30) and a control group (n=24). The patients in the two groups were all treated by oral administration of Gliguidon or subcutaneous injection of insulin with acupuncture at Ganshu (BL 18), Weiwanxiashu (EX-B 3), Shenshu (BL 23), Guanyuan (CV 4) and other acupoints added in the acupuncture group, for 30 days.</p><p><b>RESULTS</b>The total effective rate was 93.3% in the acupuncture group and 66.7% in the control group. After treatment, blood beta2-microglobulin (beta2-MG), and urine beta2-MG in the acupuncture group decreased significantly with a significant difference as compared with those in the control group; total cholesterol (TC) and triglyceride (TG) significantly decreased and high density lipoprotein (HDL) significantly increased in the acupuncture group with significant differences compared with the control group.</p><p><b>CONCLUSION</b>Acupuncture can improve lipid metabolism and protect the renal function of the patient with early metaphase diabetes.</p>

Identification of a highly conserved domain that suppresses the DNA-binding domain-DNA interactions in the androgen receptor / 中南大学学报(医学版)

OBJECTIVE@#To determine the gene regulation of androgen receptor (AR).@*METHODS@#Gel shift assay, protein-protein pull down assay, western blot and technique of site-directed mutagenesis were used to study the gene regulation of AR.@*RESULTS@#The N terminal of AR contained an inhibitory domain located in an 81-amino acid segment lying upstream of the DNA-binding domain (DBD). The inhibitory domain interacted directly with DBD and repressed DBD binding to the ARE. Mutations of the conserved amino acid residues (K520E and R538E) within the inhibitory domain decreased its inhibiting ability in vitro and increased AR trans-activation in vivo.@*CONCLUSION@#These data demonstrated the existence of a novel inhibitory domain in the N-terminal part of AR, which might play important role in the regulation of AR trans-activation.

The change of circulating endothelial cell in blood of rats and pulmonary small artery vascular endothelial cell under acute hypoxia / 中国应用生理学杂志

<p><b>AIM</b>To investigate changes of VEC and CEC under acute hypoxia.</p><p><b>METHODS</b>Observe CEC in blood under acute hypoxia morphologically and count the number of CEC by optical microscope, measure LDH activity of young CEC and VEC by histochemical staining image analysis.</p><p><b>RESULTS</b>LDH activities of VEC in hypoxic groups are lower than that in the group before hypoxia and decrease progressively with hypoxia time. LDH activities of young CEC in groups after hypoxia and before hypoxia are the same and are apparently lower than that of VEC. Before hypoxia most of CEC are aging, the number of CEC from hypoxic groups is greater than that before hypoxia and increases progressively with hypoxia time and most of CEC from hypoxic groups are young.</p><p><b>CONCLUSION</b>The morphology and number of CEC may reflect the extent to which the vascular is injured. LDH activity of VEC may reflect the transformation from VEC into CEC. LDH activity of young CEC may reflect the extent to which the VEC is injured when falling from vascular wall.</p>