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Axl is a receptor tyrosine kinase which plays an important role in multiple human malignancies. The Axl expression was examined in several hepatocellular carcinoma(HCC) cell lines, paired tumor and nontumorous samples. Then, we examined cell growth curve, cell apoptosis and cell migration in SMMC-7721 cells over-expressed with Axl or siRNA against Axl, respectively. Finally, the prognostic value of Axl was investigated in a prospective cohort of 246 consecutive HCC patients undergoing curative hepatoectomy. We found Axl was positive in 22% of examined tumor tissues and all four cell lines. Over-expressing Axl in SMMC-7721 cells accelerated cell growth, cell migration and inhibited cell apoptosis, while knock-down of Axl exerted opposite effect. Axl expression was closely associated with serum AFP, multiple tumors, absence of encapsulation, microvascular invasion, and advanced BCLC or TNM stage. Patients with positive Axl staining had a higher 5-year recurrence rate (92% vs. 71%, P<0.001) and a lower 5-year survival rate (9% vs. 48%, P<0.001) than those with negative staining. The multivariate analyses showed that Axl expression was an independent factor for both tumor recurrence (HR: 1.725; 95% CI: 1.219-2.441) and survival (1.847; 1.291-2.642). Axl expression suggests more aggressive tumor invasiveness and predicts worse prognosis for HCC patients undergoing resection.

Background Repeat hepatectomy (re-hepatectomy) is an effective treatment for patients with intrahepatic recurrence following liver resection for hepatocellular carcinoma (HCC). Objective This study aimed to develop nomograms for predicting prognosis after re-hepatectomy. Methods The data of 635 patients who underwent re-hepatectomy for recurrent HCC at the Eastern Hepatobiliary Surgery Hospital between 2004 and 2010 were prospectively collected. Multivariable Cox regression analyses based on data obtained before and after re-hepatectomy were performed to select independent predictors of recurrence to death survival (RTDS) which were incorporated into the pre- or post-re-hepatectomy nomograms. Discrimination and calibration of the nomograms were measured using the concordance index (C-index), Kaplan–Meier curves, and calibration plots. Results The 1-, 3- and 5-year overall survival rates were 96.9, 74.8, and 47.8 %, respectively, and the corresponding RTDS rates were 75.8, 45.7, and 37.6 %, respectively. Tumor size and number at the initial and recurrent stages, time to recurrence from the initial hepatectomy, hepatitis B virus deoxyribonucleic acid level and microvascular invasion were selected into the two nomograms. The C-indexes for predicting RTDS were 0.72 [95 % confidence interval (CI) 0.70–0.74] and 0.77 (95 % CI 0.74–0.80) for the pre- or post-re-hepatectomy nomograms, respectively. The calibration curves for the probability of 5-year RTDS after re-hepatectomy showed optimal agreement between the prediction shown in the nomograms and the actual observations. Both nomograms were able to accurately stratify patients into four distinct incremental prognostic subgroups. Conclusion The proposed nomograms have shown accurate RTDS prediction for patients with intrahepatic recurrent HCC.

Background Hepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC. Methods Data on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group) and did not receive it (non-AVT group). Logistic regression was used to identify the independent factors for viral reactivation. The tumor recurrence and overall survival (OS) rates were analyzed using the Kaplan–Meier method. Recurrence patterns were also investigated. Results HBV reactivation developed in 10.8% (58/538) of patients after PRFA. AVT was associated independently with decreased viral reactivation (odd ratio: 0.061, 95% confidence interval: 0.018–0.200). In 215 pairs of patients obtained after PSM, the AVT group had lower 1-, 3-, and 5-year recurrence rates (24%, 55%, and 67% vs 33%, 75%, and 85%, respectively) and higher 1-, 3-, and 5-year OS rates (100%, 67%, and 59% vs 100%, 52%, and 42%, respectively) than non-AVT group ( P  < 0.001 for both). Additionally, the relapses in distant hepatic segments and the late recurrence after 2 years of PRFA were significantly reduced in the AVT group (78/215 vs 111/215 vs., P  = 0.001; 39/109 vs. 61/91, P  = 0.012, respectively). Conclusions AVT reduced late and distal intrahepatic recurrence and improved OS in patients undergoing PRFA for HBV-related HCC by inhibiting viral reactivation.

Rat ovarian follicle culture, as a novel bioassay, is adopted in this study to explore the effects of cadmium chloride (CdCL2) on folliculogenesis and oocyte maturation in vitro; the feasibility for its application on detection of possible effects of chemicals on reproduction is discussed and evaluated as well. The results showed that follicle growth, differentiation, and steroidogenesis were significantly disturbed by ≥1.2 μg/mL CdCl2. The germinal vesicle breakdown of oocyte was also disturbed dose-dependently after the culture follicles were exposed to ≥1.6 μg/mL CdCl2. Exposure to CdCl 2 with concentrations of 1.6 μg/mL on day 2 had caused significant reduced ( p < 0.05) survival rate and rate of antral follicles, and increased abnormal follicle rate significantly, compared to the group exposed on day 6. Rat preantral follicle culture is a potential tool to assess the hazards of chemical compounds on female fertility and can be used to elucidate their mechanisms of actions.

Background The impact of different causative factors of intrahepatic cholangiocarcinoma (ICC) on disease outcome remains largely unknown. This study aimed to evaluate the prognosis of ICC patients with different pathogenic factors after hepatectomy. Methods Data of 731 consecutive patients undergoing R0 liver resection for ICC at The Eastern Hepatobiliary Surgery Hospital between 2004 and 2010 were analyzed. These patients were divided into the hepatitis B virus-related (HBV-ICC, n  = 519), hepatolithiasis-related (stone-ICC, n  = 87), HBV plus hepatolithiasis-related (HBV/stone-ICC, n  = 45), and other etiologies-related (other-ICC, n  = 80) ICC groups. Propensity score matching (PSM) was used to eliminate the baseline differences between these groups. Results In these four groups, the 5-year tumor recurrence and overall survival (OS) rates were 75.4, 90.3, 83.0 and 81.9%, and 32.7, 16.3, 17.7 and 22.6%, respectively. The significant differences in recurrence and OS were identified between the HBV- and stone-ICC groups (both p  < 0.001). In these two groups, most of the independent prognostic predictors were similar, but tumor diameter >5 cm was demonstrated as a risk factor in the HBV-ICC patients only, and surgical margin <1 cm and human epidermal growth factor receptor 2-positive were demonstrated as risk factors in the stone-ICC patients only. With PSM, 75 patients in each of the HBV- and stone-ICC cohorts were created, and the 5-year recurrence and OS rates were 69.9 versus 88.6, and 34.6 versus 19.2%, respectively ( p  = 0.017, 0.027). Conclusion Patients with HBV-ICC achieved better outcomes than those with stone-ICC. This prognostic difference was probably associated with biological malignant invasiveness rather than tumor stage.

Preantral follicle in vitro culture systems have been successfully or nearly successfully established for sheep, pig and mouse, and applied on follicle development and regulation research on reproductive biology and physiology. However, there have been few studies concerning rat preantral follicle in vitro development. The objective is to establish an in vitro culture system for rat preantral follicles which can be used for reproductive biology and toxicology research. Rat preantral follicles are mechanically separated, cultured in vitro in single follicle mode for continuous 12 days using 96-well plates, and then administrated ovulation induction. The observation on follicle development, hormone level, and ovum formation are recorded and assessed. Taking in vivo growth and in vitro maturation of ocytes group as control group, in vitro growth and maturation of oocytes group is assessed to see whether this in vitro culture method is successful. The conditions for rat follicle culture are determined based on the mouse pre-antral follicle culture. The in vitro culture system for rat preantral follicles established in this study is feasible and successful, and can serve as model for reproductive biology and toxicology research.

Abstract Background Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) may optimize individualized treatment decision-making. This study aimed to investigate the prognostic differences between HCC patients undergoing liver resection (LR) and liver transplantation (LT) based on predicted MVI risks. Methods We analysed 905 patients who underwent LR, including 524 who underwent anatomical resection (AR) and 117 who underwent LT for HCC within the Milan criteria using propensity score matching. A nomogram model was used to predict preoperative MVI risk. Results The concordance indices of the nomogram for predicting MVI were 0.809 and 0.838 in patients undergoing LR and LT, respectively. Based on an optimal cut-off value of 200 points, the nomogram defined patients as high- or low-risk MVI groups. LT resulted in a lower 5-year recurrence rate and higher 5-year overall survival (OS) rate than LR among the high-risk patients (23.6% vs 73.2%, P < 0.001; 87.8% vs 48.1%, P < 0.001) and low-risk patients (19.0% vs 45.7%, P < 0.001; 86.5% vs 70.0%, P = 0.002). The hazard ratios (HRs) of LT vs LR for recurrence and OS were 0.18 (95% confidence interval [CI], 0.09–0.37) and 0.12 (95% CI, 0.04–0.37) among the high-risk patients and 0.37 (95% CI, 0.21–0.66) and 0.36 (95% CI, 0.17–0.78) among the low-risk patients. LT also provided a lower 5-year recurrence rate and higher 5-year OS rate than AR among the high-risk patients (24.8% vs 63.5%, P = 0.001; 86.7% vs 65.7%, P = 0.004), with HRs of LT vs AR for recurrence and OS being 0.24 (95% CI, 0.11–0.53) and 0.17 (95% CI, 0.06–0.52), respectively. The 5-year recurrence and OS rates between patients undergoing LT and AR were not significantly different in the low-risk patients (19.4% vs 28.3%, P = 0.129; 85.7% vs 77.8%, P = 0.161). Conclusions LT was superior to LR for patients with HCC within the Milan criteria with a predicted high or low risk of MVI. No significant differences in prognosis were found between LT and AR in patients with a low risk of MVI.

Most previous studies focused on a small number of heat shock proteins (Hsps) and their relationships with embryogenesis, and the actual roles of these Hsps in normal and abnormal embryonic development remain unclear. It was found in the present systemic study that except for Grp170, whose expression was not detectable at GD18, all 19 Hsps of Hsp70, Hsp90 and Hsp110 families were expressed in the normal development of embryonic palate tissue in mice, but their expression patterns varied with different Hsps, presenting as a correlation with the developmental phases. In the treatment group by all-trans retinoic acid (atRA), the messenger RNA (mRNA) abundance of HspA1A, HspA1L, HspA8, HspA9, HspA12A, HspA12B, HspA13, HspA14, Hsp90AA1, Hsp90AB1, Grp94, Trap1, Hsp105, Hsp110 and Grp170 was higher in the palates at GD11 (the beginning of palate development), the mRNA abundance of HspA1A, HspA12A and HspA12B was higher at GD18 (before birth) and an mRNA expression peak of HspA1L, HspA8, HspA9, Hsp90AA1, Grp94, Hsp110 and Grp170 was observed at GD17. The mRNA abundance of most genes in atRA-induced cleft palates of the treatment group was different from that of the control group. Grp78, HspA14 and Hsp105 were closely associated with the normal palate development and cleft palate in mouse embryo, possibly as palate development-related genes. Except Grp170, the other genes may be closely associated with the development of mouse palates through participating in the stress response process and/or the antiapoptosis process.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.Conclusion: RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

A Gram-strain-negative, rod-shaped, aerobic bacterium, designated strain TRM 85114T, was isolated from the Jincaotan wetland in the Pamir Plateau of China. This strain grew optimally at 30 °C and pH 6.0 in the presence of 3% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain TRM 85114T was affiliated with the genus Halomonas, and shared high sequence similarity with Halomonas korlensis XK1T (97.3%) and Halomonas tibetensis pyc13T (96.4%). Strain TRM 85114T contained C16:0 and C19:0 cyclo ω8c as primary cellular fatty acids, Q-9 as predominate respiratory quinone, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phospholipids of unknown structure containing glucosamine, unidentified aminophospholipids, unidentified lipids and three unidentified phospholipids as the major polar lipids. The complete genome of TRM 85114T comprised 3,902 putative genes with a total of 4,126,476 bp and a G + C content of 61.6%. The average nucleotide identity and digital DNA–DNA hybridization values between strain TRM 85114T and related type Halomonas strains of H. korlensis XK1T, H. tibetensis pyc13T, Chromohalobacter salexigens DSM 6768T, and Halomonas urumqiensis BZ-SZ-XJ27T were 75.4–88.9% and 22.9–39.2%, respectively. Based on phenotypic, chemotaxonomic, and molecular features, strain TRM 85114T represents a novel species of the genus Halomonas, for which the name is proposed as Halomonas jincaotanensis sp. nov.. The type strain is TRM 85114T (CCTCC AB 2021006T = LMG 32311T). The amount of 1-naphthylamine degradation by strain TRM 85114T reached up to 32.0 mg/L in 14 days.