Background: Patients with different karyotypes had different prognosis in t(8;21) acute myeloid leukemia (AML). Cytarabine (Ara-C) plays an important role as consolidation therapy in t(8;21) AML. T(8;21) AML patients with different karyotypes responded differently to post-remission therapy with Ara-C. However, the optimum dose of Ara-C in patients with different karyotypes remains unclear.
Xiaguan Tuo Tea is largely consumed by the Chinese, but there is little research into the microbial diversity and component changes during the fermentation of this tea. In this study, we first used fluorescence in situ hybridization (FISH), next-generation sequencing (NGS) and chemical analysis methods to determine the microbial abundance and diversity and the chemical composition during fermentation. The FISH results showed that the total number of microorganisms ranges from 2.3×102 to 4.0×108 cells per gram of sample during fermentation and is mainly dominated by fungi. In the early fermentation stages, molds are dominant (0.6×102~2.8×106 cells/g, 0~35 d). However, in the late stages of fermentation, yeasts are dominant (3.6×104~9.6×106 cells/g, 35~56 d). The bacteria have little effect during the fermentation of tea (102~103 cells/g, <1% of fungus values). Of these fungi, A. niger (Aspergillus niger) and B. adeninivorans (Blastobotrys adeninivorans) are identified as the two most common strains, based on Next-generation Sequencing (NGS) analysis. Peak diversity in tea was observed at day 35 of fermentation (Shannon–Weaver index: 1.195857), and lower diversity was observed on days 6 and 56 of fermentation (Shannon–Weaver index 0.860589 and 1.119106, respectively). During the microbial fermentation, compared to the unfermented tea, the tea polyphenol content decreased by 54%, and the caffeine content increased by 59%. Theanine and free amino acid contents were reduced during fermentation by 81.1 and 92.85%, respectively.
The prognostic significance of loss of X chromosome (-X) in t(8;21) acute myeloid leukemia (AML) remains unclear. We evaluated the role of -X in 158 female patients with t(8;21) AML collected retrospectively from 15 Chinese AML study groups. Patients with -X accounted for 25.3% and showed a significantly higher complete remission rate, better 3-year cumulative incidence of relapse (25.2 vs. 50.5%, p = 0.013), relapse-free survival (69.4 vs. 44.7%, p = 0.025), and overall survival (77.4 vs. 52.7%, p = 0.026) compared with those without -X. Patients with -X were more likely to achieve minimal residual disease negativity (risk ratio = 1.62; p = 0.020). A Multivariate analysis adjusting for age, white blood cell, KIT-D816 mutation, high-dose cytarabine consolidation therapy, and allogeneic hematopoietic stem-cell transplantation showed -X to be an independent favorable prognostic factor. Our results suggest that -X may be associated with better outcomes in patients with t(8;21) AML.
Objective To investigate the predictive value of FibroScan for liver ascites caused by cirrhosis.Methods A total of 651 patients with liver cirrhosis were subjected to FibroScan examination in People’s Liberation Army 302 Hospital from December 2009 to June 2010 and were enrolled in the present study.Among the patients,185 suffered from liver cirrhosis with ascites(all patients initially had ascites) and 466 did not suffer from ascites.After obtaining the FibroScan value,the difference in liver cirrhosis caused by chronic hepatitis B and liver cirrhosis caused by chronic hepatitis C and other liver cirrhosis were analyzed.A Receive Operating Characteristic(ROC) curve was drawn and the area under the curve(AUROC) was analyzed to determine the cutoff value,sensitivity,specificity,positive predictive value,and negative predictive value of the FibroScan for predicting ascites.Results The FibroScan value of patients with liver cirrhosis caused by chronic hepatitis C [27.0(20.6-44.3)kPa] was obviously higher than that of patients with liver cirrhosis caused by chronic hepatitis B [23.6(13.7-37.7)kPa,P < 0.01].Moreover,the average FibroScan value of the other liver cirrhosis patients was 23.8(13.7-50.1)kPa,which isn′t different from the FibroScan value of liver cirrhosis patients with chronic hepatitis C or B.The FibroScan median of the liver cirrhosis patients with ascites [45.0(33.1-69.1) kPa] was significantly higher than that of the liver cirrhosis patients without ascites [19.1(12.1-26.3) kPa,P < 0.01].The AUROC value of the FibroScan for predicting ascites was 0.895(95% CI: 0.869-0.918),the cutoff value of the diagnosis was 27.7 kPa,sensitivity was 88.2%,specificity was 81.5%,the positive predictive rate was 66.5%,and the negative predictive rate was 94.3%.Conclusion FibroScan can effectively predict the likelihood of ascites formation in patients with cirrhosis and has value for clinical application.
Abstract Background : PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. Methods: PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. Results: PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P=0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. Conclusion: This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.
Objective
To analyze the influencing factors of prognosis of early mixed signet ring cell carcinoma (SRCC) of the stomach with signet ring cell ratio less than 50%.
Methods
The clinical data of 110 patients with SRCC who underwent radical resection of gastric cancer in the First People's Hospital of Ziyang from January 2014 to December 2016 were retrospectively analyzed. The postoperative pathology was confirmed as mixed SRCC of the stomach with signet ring cell ratio less than 50%. The patients were followed up, and the end point of the follow-up was all-cause death. The prognostic influencing factors of SRCC patients were analyzed.
Results
The median follow-up time was 32.5 months (0.9-70.0 months), with the median overall survival (OS) time of 40.0 months (7.0-61.0 months) and the 3-year OS rate of 46.5%. Kaplan-Meier survival analysis showed that the 3-year OS rate of age ≥60 years, male, upper stomach, tumor diameter ≥5 cm, invasion of the gastric wall, lymph node metastasis, and vascular invasion of mixed SRCC of the stomach patients was 34.3%, 31.1%, 30.0%, 33.3%, 40.7%, 28.9%, 37.5%, respectively, which was all lower than that of those with age <60 years old, female, lower stomach, tumor diameter <5 cm, non-invasive whole stomach wall, no lymph node metastasis, no vascular invasion (57.6%, 57.5%, 52.9%, 57.6%, 56.7%, 74.6%, 62.3%), and there was no statistically significant difference (all P < 0.05). Cox multivariate results showed that age ≥60 years old (OR = 1.225, 95% CI 1.089-3.481, P = 0.003), lymph node metastasis (OR = 1.077, 95% CI 1.059-2.674, P = 0.034), invasion of the whole stomach wall (OR = 1.342, 95% CI 1.117-7.225, P = 0.002), and vascular invasion (OR = 1.104, 95% CI 1.087-2.541, P = 0.018) were independent factors affecting OS of mixed SRCC of the stomach.
Conclusion
Mixed SRCC of the stomach patients with signet ring cell ratio less than 50% featured by advanced age, lymph node metastasis, invasion of the full thickness of the stomach wall, and vascular invasion have a poor prognosis.
Key words:
Stomach neoplasms; Carcinoma, signet ring cell; Signet ring cell ratio; Prognosis
Transplantation of mesenchymal stem cells (MSCs) has therapeutic effects on various diseases, while its effect on developing cirrhosis as well as the underlying mechanism remained largely unknown.Twenty C57BL/6 mice were randomly separated into 2 groups of ten each. One group received transplantation of MSCs, while the other group received saline as control. The mice then received intraperitoneal injection of carbon tetrachloride (CCl4) twice per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure, sodium balance and excretion. Transcripts of transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the mouse livers were quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this model, and compared to MSCs.Liver fibrosis, portal hypertension and sodium retention that were developed by CCl4, were all significantly alleviated by MSCs transplantation, which decreased TGFβ1 levels and increased BMP7 levels in the injured liver. MSCs were found to express extremely high levels of BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of MSCs against CCl4-induced cirrhosis.MSCs mitigate cirrhosis through their production of BMP7 against the fibrogenic effect of TGFβ1 in the injured liver.
Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.