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Objective:To investigate the clinical characteristics of pregnant women with leukemia, the condition of leukemia and the influence of clinical treatment on maternal and infant outcomes, and to explore the best clinical management method of leukemia in pregnancy.Methods:Among 79 890 pregnant and lying-in women in Qilu Hospital of Shandong University from January 2004 to December 2015, 22 cases (0.028%) were with leukemia, including 5 cases of leukemia diagnosed before pregnancy [all acute myeloid leukemia (AML)] and 17 cases of leukemia diagnosed for the first time after pregnancy [9 cases of AML, 5 cases of chronic myeloid leukemia (CML), 2 cases of acute lymphoblastic leukemia (ALL), and 1 case of chronic lymphocytic leukemia (CLL)]. According to the gestational weeks of admission and confirmed gestational weeks of leukemia, the 22 patients were divided into early-stage group (initial gestational week < 14 weeks, 5 cases), mid-stage group (newly diagnosed gestational week ≥ 14 weeks and < 28 weeks, 11 cases), and late-stage group (newly diagnosed gestational week ≥ 28 weeks, 6 cases, including 2 cases with previous diagnosis of leukemia). The final pregnancy outcomes included abortion, induced labor, premature delivery, full-term delivery and maternal and infant death. The effects of clinical treatment and obstetric treatment of leukemia on the final maternal and infant outcomes, follow-up to understand the progress of primary disease and fertility of pregnant women, and the impact of leukemia and pregnancy treatment on long-term health status of infants were analyzed.Results:Among 22 patients with leukemia in pregnancy, 14 cases (63.6%) (5 cases in early-stage group and 9 cases in mid-stage group) choosed to give up pregnancy, including 4 cases of early pregnancy abortion and 10 cases of mid pregnancy induced abortion; 12 cases of 14 cases were induced abortion or induced labor after leukemia remission induced by advanced chemotherapy. The remaining 8 patients (2 cases in mid-stage group and 6 cases in late-stage group) continued pregnancy and gave birth to live infants, of which 3 cases received chemotherapy before delivery.Conclusions:Gestational leukemia is a high-risk obstetric case, but it is still expected to achieve good pregnancy outcome under good management and treatment. On the basis of following the principles of leukemia treatment, according to the gestational weeks and patients' wishes, the individualized clinical management plan is formulated, and the accurate chemotherapy timing is conducive to the prognosis of mother and infant.
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Enrichment of trace bioactive constituents and metabolites from complex biological samples is chal-lenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@-SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80％ after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In com-parison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and charac-terization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.
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Childhood obesity is one of the major public health problems in the 21st century.The specific pathogenesis of obesity in children is still not very clear.It is currently believed that it may be caused by multiple factors including heredity,diet,and physical activity.The mitochondrial dysfunction plays an important role in the development of obesity.Mitochondria are important sites for energy metabolism in human body,and the normal function depends on the regulation of both nuclear and mitochondrial genes.In addition,due to the maternal inheritance,mitochondrial DNA can be passed to the next generation,which explains why some studies show larger correlation for BMI between mothers and their children than between fathers and their children.Therefore,mitochondrial genes are likely to be an important part of the development of childhood obesity.This article reviews the association and possible mechanisms of mitochondrial DNA and childhood obesity.
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Objective To explore the significance of the cut point of peak level of luteinizing hormone (LH) in gonadotropin-releasing hormone (GnRH) agonist test in the diagnosis of precocious puberty in obese girls.Methods According to the diagnostic criteria of children's central precocious puberty diagnosis consensus (2015),796 cases of precocious puberty (peak level of LH ≥3.3 IU/L) in Children's Hospital of Zhejiang University School of Medicine from January 2014 to December 2015 were divided into normal weight group (573 cases),overweight group (170 cases) and obesity group (53 cases).The 3 groups were compared in terms of basic level of LH,basic level of follicle stimulating hormone (FSH),peak level of LH and FSH,ratio of LH (peak)/FSH (peak),sex hormone binding protein (SHBG),and children with 3.3 IU/L ≤peak level of LH ＜5.0 IU/L were followed up.The accuracy of the diagnosis of central precocious puberty using peak level of LH was analyzed by using receiver operating characteristic (ROC) curve.Results The median of LH (peak) in the obese group was 6.92 IU/L,the median of SHBG was 46.52 nmol/L,the median of LH (peak) in normal weight group was 8.92 IU/L,and the median of SHBG was 87.28 nmol/L.There were significant differences between the 2 groups (P ＜ 0.05,0.001).A total of 89 cases in normal weight group and 65 cases of obesity/overweight group (3.3 IU/L ≤peak level of LH ＜5.0 IU/L) were followed up for 1 year,and 18 cases in normal weight group and 33 cases in obesity/overweight group developed to central precocious puberty,while the number of cases in the 2 groups was significantly different (P ＜0.001).The ROC curve analysis showed that the cut point of peak level of LH was 4.16 IU/L,the sensitivity was 0.606,the specificity was 0.656,and the Jordan index was the largest (0.344).Conclusions The peak level of LH in GnRH agonist test is important for the diagnosis of central precocious puberty in girls,but the effect of body mass index on its cut point needs to be considered.
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Objective To evaluate the predictive value of Admission-Rockall Score (aRS), Full-Rockall Score ( fRS ), Glasgow-Blatchford Score ( GBS ) and AIMS65 scoring systems for rebleeding, mortality, transfusion and clinical intervention of patients with acute nonvariceal upper gastrointestinal bleeding ( ANVUGIB). Methods A retrospective study was performed on the data of 294 ANVUGIB inpatients in the Department of Gastroenterology of Tianjin Medical University General Hospital from January 2015 to September 2016. Each patient was graded using the four scoring systems. The area under the receiver-operating characteristic curve ( AUC) about rebleeding, mortality, blood transfusion and clinical intervention was calculated using each system. Results For predicting rebleeding, fRS (AUC＝0. 696) and GBS (AUC＝0. 697) were both superior to aRS (AUC＝0. 609, P＜0. 05) and AIMS65 (AUC＝0. 571, P＜0. 05), and there was no significant difference on AUC between fRS and GBS (P＞0. 05). For predicting mortality, the AUC of aRS, fRS, GBS and AIMS65 were 0. 755, 0. 791, 0. 818, and 0. 780, respectively, and there were no significant differences (P＞0. 05). There were no significant differences in the predicting transfusion among four scoring systems, and the AUC was 0. 625, 0. 626, 0. 697 and 0. 658, respectively. Regarding clinical intervention treatment, fRS (AUC＝0. 661) was superior than that of aRS (AUC＝0. 520, P＜0. 05) and AIMS65 (AUC＝0. 545, P＜0. 05), and the AUC of GBS and three other scoring systems had no significant differences (P＞0. 05). Conclusion The four scoring systems are all with good predicting value on mortality of patients with ANVUGIB, while not on other aspects including rebleeding, transfusion and clinical intervention. fRS has a slightly better value on prediction of rebleeding and clinical intervention, and GBS is slightly better on prediction of rebleeding.
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Objective To study the application of hepatamethine cyanine near-infrared fluorescence (NIRF) dye IR-783 in the mouse models of human liver cancer exenografts, and to analyze the molecular mechanisms of the NIRF dye targeting tumor cells.Methods Luciferase-tagged HepG2 cells were inoculated subcutaneously into the nude mice.We detected the correlation of NIRF intensity and bioluminescence intensity (BIL) in the tumor region.Patient-derived xenograft (PDX) model was established in mouse by subrenal capsular implantation of clinic liver cancer specimen.After injecting the IR-783 dye, the interface between mouse kidney and the xenograft tumors was confirmed by NIRF analysis, and the tumor tissue in kidney was observed by pathology using H&E staining.The expression of CEA, AFP, HIF1α and OATP3A1 in the liver cancer tissue was detected by immunohistochemical staining.The intracellular retention of NIRF dyes was observed under fluorescence microscope after adding Mito Tracker or Lyso Tracker into cultured HepG2 cells.We added IR-783 in a co-culture system of HCCs and normal liver cells to test the specifical identification ability of IR-783 of the liver cancer cells.Results There was a good correlation between NIRF intensity and BIL intensity of the subcutaneous liver cancer xenograft region in nude mice.The margin between the mouse kidney tissue and xenograft tumors was clearly identified by IR-783.Compared with normal kidney tissue, CEA, HIF1α, OATP3A1 and AFP were highly expressed in the tumor region detected by IHC staining.The NIRF dye IR-783 was mainly accumulated in the mitochondria and lysosomes of cancer cells.GFP-tagged HepG2 cells could be recognized directly, whereas red fluorescence was not detected in normal liver cells.Conclusions IR-783 is a novel near-infrared fluorescent dye with tumor targeting and imaging properties.Its targeting ability may be related to the high expression of HIF1α and OATP3A1 in the liver cancer tissue.
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Objective To investigate the mechanism of bone morphogenetic protein 4(BMP4) in the genesis of Barrett′s esophagus.Methods Human esophageal epithelial cell (HEEC) and MRC-5 were cultured.The effects of different concentration of BMP4 and different pH value of hydrochloric acid or glycocholic acid on the expression of caudal-related homeobox transcription factor 2(CDX2) in HEEC were detected by real time polymerase chain reaction.The effects of different pH value of hydrochloric acid or glycocholic acid on BMP4 expression in MRC-5 were also investigated.Independent sample t test was performed for statistical analysis.Results After HEEC stimulated by BMP4 at 0.1, 1.0, 10.0 and 100.0 ng/mL, the relative quantity expressions of CDX2 were 1.617±0.246, 2.489±0.455, 5.629±0.449 and 13.670±1.689, respectively, which were higher than those of control group (1.000±0.043, 1.029±0.094, 1.001±0.002 and 1.049±0.051, respectively), and the differences were statistically significant (t=2.47, 3.14, 10.31, 7.47;all P<0.05).After MRC-5 stimulated by acid at pH four or five, or glycocholic acid at pH four or five, the relative quantity expressions of BMP4 were 2.430±0.105, 2.394±0.145, 125.900±12.620 and 2.128±0.215, respectively, which were higher than those of control group(1.025±0.095, 0.999±0.007, 1.060±0.138 and 0.893±0.110,respectively), and the differences were statistically significant (t=9.94, 9.59, 9.89, 5.11;all P<0.01).Conclusion BMP4 can increase the expression of CDX2 in HEEC, which promote the genesis of Barrett′s esophagus.
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Objective To study the tumor targeting ability and application of farnesylthiosalicylic Acid (FTS) and heptamethine carbocyanine fluorescent dye-mediated near-infrared imagine in living animals, and confirm the inhibitory effect of this compound on growth of tumor cells.Methods Human breast cancer cell line MCF-7, glioma cell line U251 and prostate cancer cell line PC3 were cultured to logarithmic growth phase, and different concentrations of FTS and FTS-IR783 were added, respectively.We observed the inhibitory effect of those two compounds on the growth of tumor cells.Under fluorescence microscopy, specific accumulation of FTS-IR783 in these tumor cells was observed.The tumor cells (1×106) were transplanted subcutaneously into nude mice.These mice were subjected to intraperitoneal injection of FTS-IR783 (10 nmol/mouse) two weeks later.In the in vivo imaging, near infrared fluorescence signal and tumor volume were measured and their correlation was analyzed.Results Compared with FTS, FTS-IR783 significantly inhibited the growth of MCF-7, U251 and PC3 cells in vitro.FTS-IR783 was specifically uptaken by these three kinds of tumor cells, showing strong near infrared fluorescence in cell agglomerates.After subcutaneous injection of FTS-IR783, the correlation between fluorescence intensity and tumor volume was 0.987, 0.998 and 0.971, respectively.Conclusions The compound of FTS conjugated with near infrared fluorescent dye IR-783 can specifically recognize tumor cells, in both in vitro and in vivo imaging.At the same time, the compound can significantly inhibit the growth of tumor cells, and may be expected to become a new potential targeted drug.
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Objective To establish a patient-derived gastric cancer xenograft( PDX) model in nude mice and to in-vestigate the application of near infrared fluorescent ( NIRF) dye IR-783 in in vivo imaging of gastric cancer xenograft mod-els.Methods Fresh human gastric cancer tissue was taken and transplanted into the subrenal capsule of nude mice to es-tablish the xenograft model.When the transplanted tumors grew,took part of the tumor tissue to do HE staining and compare the structural characteristics with the primary tumor.Another portion of the tumor was xenografted into nude mice subcutane-ously.Twenty days later,the tumor-bearing mice were injected intraperitoneally with IR-783 dye (10μM) in a dose of 100 mg/20 g.The intensity of the tumor image was monitored by optical NIRF imaging.The correction between tumor volume and fluorescence intensity was analyzed.Finally,the expression of OATP1B3 and HIF1αin the xenografted tumor tissue was detected by immunohistochemistry.Results We successfully established three patient-derived xenograft ( PDH) models of human gastric cancer.The transplanted tumor tissues maintained the histological characteristics of the primary tumor well.NIRF signal can be detec ted in subrenal capsule of the xenografted nude mice.The correlation between tumor size and fluorescence intensity in the PDX models reached higher than 98%.Strong positive expressions of HIF1αand OATP1B3 in the tumor tissues were detected.Conclusions NIRF dye IR-783 can be specifically accumulated at the tumor site,therefore, can be used to detect PDX in vivo early.The tumor targeting property may be related to the expression of OATP1B3 and HIF1α.
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Objective To investigate the value of 18F-FDG PET/CT for differentiating multiple myeloma from bone metastases with undetermined origin.Methods A retrospective study was performed on patients with multiple bone destructions and without extraosseous primary malignant tumor in 18F-FDG PET/CT imaging.A total of 26 patients (12 males,average age 55.4 years) with multiple myeloma and 20 patients (9 males,average age 50.2 years) with multiple bone metastases confirmed by biopsy or histopathology from January 2011 to December 2013 were included into this study.The characteristics of 18F-FDG PET/CT and urine Bence-Jones protein were used to establish the diagnostic criteria.Myeloma was diagnosed if two or more of the following conditions could be satisfied:more than 10 bone lesions,osteolytic or mixed bone destruction,SUVmax＜4.0,and positive urine Bence-Jones protein.Two-sample t test and x2 test were used.Results The average number of bone lesions in multiple myeloma patients was 15.8,which was more than that (7.8) in patients with bone metastases.About 71.8％ (296/412) of bone lesions in multiple myeloma and 28.8％ (45/156) of bone metastases were osteolytic.The percentage of osteolytic lesions was significantly higher in multiple myeloma (x2=87.2,P＜0.05).The SUVmax of bone lesions of multiple myeloma and bone metastases were 3.81 ±2.17 and 5.82± 3.44 (t =8.29,P＜0.05) respectively.According to the diagnostic criteria,the sensitivity,specificity and accuracy of 18F-FDG PET/CT for the differentiation of myeloma from bone metastases were 88.5％ (23/26),85.0％ (17/20) and 87.0％ (40/46).Its diagnostic efficiency was higher than urine Bence-Jones protein (sensitivity:65.4％ (17/26);x2=3.90) and original 18 F-FDG PET/CT evaluation (specificity:10/18,accuracy:64.1％ (25/39);x2 =3.99,6.12) respectively (all P＜0.05).Conclusion Combining the evaluation of structural properties and metabolism on 18F-FDG PET/CT with urine Bence-Jones protein level may provide additional value for the differentiation of multiple myeloma from bone metastases with undetermined origin.
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Prostate cancer is one of the most common malignant tumors in men and related studies have achieved great breakthrough in recent years.But because of the lack of effective in vivo animal models, the process to translate basic research into clinical application has been severely hampered.Patient derived prostate tumor xenograft ( PDPTX) model is an ideal animal model in which freshly isolated tumor tissues from patients were inoculated into immunodeficient mice.This model can duplicate the heterogeneity of primary tumor in a better way and keep the tumor complexity at molecular, genetic and pathological levels.Particularly, the PDPTX model, in which the isolated tumor tissue is inoculated under the renal capsule, is even better, because it solves the clrawbacks of traditional subcutaneous inoculation model.In traditional mod-els, the success rate is low, it’s not easy for lower grade tumor to form xenograft, and it’s not easy to reconstruct metasta-sis, etc.PDPTX provides a more ideal in vivo model for prostate cancer studies.It has irreplaceable advantages, especially in target therapy, new drug screening and individualized tumor treatment.
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Objective To inVestigate the effect of emodin on hyPertroPhic scar fibroblasts ( HSFs ) and exPlore the underlying mechanism. Methods HSFs were treated by emodin at final concentrations of 0,20,40,and 80 μmol·L-1, resPectiVely,in the cultural media. Forty_eight hours later,the cells were subjected to MTS assay and flow cytometry assay with annexin V and ProPidium iodide as dyeing indicators. Whole cell lysates from the cells of eVery grouP were subjected to Western blotting to measure the Protein exPression leVels of ERK1∕2,Bcl_2,Mcl_1 and RIP1. Results The cell Viability of HSFs was inhibited by emodin in a dose dePendent manner. The mortality rate of HSFs treated with emodin for 48 h at the concentrations of 40 and 80 μmol·L-1 were 28. 6%and 68. 0%,resPectiVely,which was significantly higher than that of the control grouP ( P<0.01).Pretreatmentwith Z_VAD_FMK could Partially reduce the mortality caused by emodin (P<0.05).PhosPhorylation of ERK1∕2 and the exPression of RIP1 and Mcl_1 were inhibited by emodin. Conclusion Down regulation of ERK1∕2,RIP1 and Mcl_1 by emodin may account for the inhibited Proliferation and increased cell death of HSFs.
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Objective:To investigate the differentially expressed genes of gastric mucosa of precancerous lesion of chronic atrophic gastritis (CAG) in rats intervented by promoting blood flow therapy of TCM,and to analyze its mechanism at genetic level. Methods:The model of precancerous lesion of CAG rats was induced by spring insertion and intragastric administration of NaCl solution and hot paste. To detect the differentially expressed genes of precancerous lesion of CAG rats by gene chip technology,and the main differentially expressed genes were indentified by real-time PCR. Results:Compared with blank group,HSP70 and ptk2 significantly reduced in natural recovery group,the HSP70 expression increased signifi cantly after being treated with supplementing qi for promoting blood flow,and ptk2 expression increased obviously after being treated with regulating qi and promoting blood flow. The results of real-time PCR in expression level of HSP70mRNA and ptk2mRNA were the same as that of the gene chip technology. Conclusion:Supplementing qi for promoting blood flow can upregulate HSP70,thus inhibit precancerous lesion of CAG in rat gastric mucosal cell apoptosis and promote mucosal repair; Regulating qi and promoting blood flow can up-regulate ptk2,sequentially regular remodeling of actin cytoskeleton and promote repairing and healing of injury gastric mucosal. These may be one of mechanism that supplementing qi for promoting blood flow and regulating qi and promoting blood flow treat precancerous lesion of CAG.