Non-contrast enhanced MRI for efficiency evaluation of high-intensity focused ultrasound in adenomyosis ablation.

OBJECTIVE: To investigate the value of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) in evaluating the therapeutic effect of high-intensity focused ultrasound (HIFU) in adenomyosis ablation. MATERIAL AND METHODS: One hundred eighty-nine patients with adenomyosis were treated with HIFU. The ablation areas on T2WI and DWI sequences were classified into different types: type I, relatively ill-defined rim or unrecognizable; subtype IIa, well-defined rim with hyperintensity; subtype IIb, well-defined rim with hypointensity. The volume of ablation areas on T2WI (VT2WI) and DWI (VDWI) was measured and compared with the non-perfused volume (NPV), and linear regression was conducted to analyze their correlation with NPV. RESULTS: The VT2WI of type I and type II (subtype IIa and subtype IIb) were statistically different from the corresponding NPV (p = 0.004 and 0.024, respectively), while no significant difference was found between the VDWI of type I and type II with NPV (p = 0.478 and 0.561, respectively). In the linear regression analysis, both VT2WI and VDWI were positively correlated with NPV, with R2 reaching 0.96 and 0.97, respectively. CONCLUSIONS: Both T2WI and DWI have the potential for efficient evaluation of HIFU treatment in adenomyosis, and DWI can be a replacement for CE-T1WI to some extent.

Specific risk factors contributing to early and late recurrences of intrahepatic cholangiocarcinoma after curative resection.

BACKGROUND: Most intrahepatic cholangiocarcinoma (ICC) patients experienced tumor recurrences even after curative resection, but the optimal cut-off time point and the specific risk factors for early and late recurrences of ICC have not been clearly defined. The objective of the current study was to define specific risk factors for early and late recurrences of ICC after radical hepatectomy. METHODS: Included in this study were 259 ICC patients who underwent curative surgery at our hospital between January 2005 and December 2009. Recurrences in these patients were followed-up prospectively. Piecewise regression model and the minimum P value approach were used to estimate the optimal cut-off time point for early and late recurrences. Then, Cox's proportional hazards regression model was used to identify specific independent risk factors for early and late recurrences. RESULTS: Early and late recurrences occurred in 130 and 74 patients, respectively, and the 12th month was confirmed as the optimal cut-off time point for early and late recurrences. Cox's proportional hazards regression model showed that microvascular invasion (HR = 2.084, 95% CI 1.115-3.897, P = 0.021), multiple tumors (HR = 2.071, 95% CI 1.185-3.616, P = 0.010), abnormal elevation of serum CA19-9 (HR = 1.619, 95% CI 1.076-2.437, P = 0.021), and the negative hepatitis B status (HR = 1.650, 95% CI 1.123-2.427, P = 0.011) were independent risk factors for early recurrence, and HBV-DNA level > 106 IU/mL (HR = 1.785, 95% CI 1.015-3.141, P = 0.044) and a hepatolithiasis history (HR = 2.538, 95% CI 1.165-5.533, P = 0.010) contributed to late recurrence independently. CONCLUSION: Specific risk factors and mechanisms may relate to early and late recurrences of ICC after curative resection.

Energy-efficient multidimensional Hellinger modulation for SPAD-based optical wireless communications.

Recently, the single photon avalanche diode optical wireless communication (SPAD OWC) has attracted much attention due to its potential underwater applications. For such system, the channel noise is additive Poisson noise (APN) rather than the commonly encountered additive white Gaussian noise (AWGN) and the corresponding maximum likelihood (ML) detection is hard to provide a useful insight into energy-efficient signal design. By using the previously proposed Hellinger distance design criterion, we design an energy-efficient multi-dimensional constellation within the nonnegative integer set by minimizing the average optical power for a fixed minimum Hellinger distance. Comprehensive simulations indicate that our designed constellation can substantially outperform the currently available pulse amplitude modulation (PAM) and squared PAM for SPAD OWC systems.

Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.

[Expression of CD90/EpCAM/CD24 in hepatocellular carcinoma cell lines at various stages of differentiation].

OBJECTIVE: To confirm the malignant phenotype of hepatocarcinoma cell (HCC) lines at various stages of differentiation (MHCC97L, MHCC97H and HCCLM3) and to explore their expression levels of cancer stem cell (CSC) markers. METHODS: The invasive and proliferative properties of each HCC line were assessed by transwell assay and the Cell Counting Kit-8 (CCK-8) colorimetric assay. Sensitivity to chemotherapy was assessed by treatment with oxaliplatin and determination of the half inhibitory concentration (IC50). The expression of CD90, EpCAM and CD24 was measured by flow cytometry. RESULTS: The number of cells that migrated through the invasion assay membrane were significantly different between the three HCC lines: HCCLM3 (30.57 +/- 8.95) more than MHCC97H (21.33 +/- 4.17) more than HCC97L (9.33 +/- 3.85), P less than 0.01. The IC50 was significantly different between the three HCC lines: HCCLM3 (36.57 +/- 6.95) mumol/L more than MHCC97H (26.35+/-3.88) mumol/L more than MHCC97L (17.68 +/- 3.25) mumol/L. The CSC marker with the highest expression on all three HCC lines was CD90 (HCCLM3: 0.92% +/- 0.21%, MHCC97H: 1.98% +/- 0.23%, and MHCC97L: 2.55% +/- 0.34%), followed by EpCAM (2.11% +/- 0.32%, 3.23% +/- 0.18%, and 4.38% +/-0.49%, respectively), and CD24 as the lowest (0.68% +/- 0.37%, 1.22% +/- 0.26%, and 1.36% +/- 0.24%, respectively). CONCLUSION: Higher expression of CSC markers on HCC lines is associated with a stronger invasive ability and higher sensitivity to chemotherapy.

Mechanism of CsGPA1 in regulating cold tolerance of cucumber.

G proteins function directly in cold tolerance of plants. However, the framework of the Gα subunit in regulating cold tolerance remains to be explored. Here, we used protein interaction techniques to elucidate cold-related pathways regulated by CsGPA1. Suppression of CsGPA1 decreased the cold tolerance of cucumber. Further protein interaction experiments showed that CsGPA1 interacted with Csa_4G663630.1 located in the cell membrane and nucleus and with CsCOR413PM2 located in the cell membrane. Csa_4G663630.1 was named CsCDL1 due to its 71% protein sequence similarity to AtCDL1, a positive brassinolide signal gene. Suppression of CsGPA1 decreased the expression of most of brassinolide-related genes (including CsCDL1) under cold stress. Principal component and linear regression analyses showed that expressions of CsGPA1 and brassinolide-related genes were positively correlated. Suppression of CsCOR413PM2 also decreased cold tolerance of cucumber. The expression and protein content of CsCOR413PM2 and CsGPA1 in CsGPA1-RNAi and CsCOR413PM2-RNAi lines were determined under cold tolerance. Only CsGPA1 silencing affected the expression and protein content of CsCOR413PM2 during cold stress. Moreover, suppression of CsGPA1 or CsCOR413PM2 decreased Ca 2+ influx at low temperature and then decreased the expression of CsICE-CsCBF. These results indicated that the CsGPA1-CsCOR413PM2-Ca2+ axis regulated the expression of CsICE-CsCBF during cold stress. In conclusion, Our results provide the first framework of CsGPA1 in regulating cold tolerance of cucumber, laying the foundation for further mechanistic studies of cold tolerance for Gα in cucumber.

Screening of Hepatocellular Carcinoma Patients with High Risk of Early Recurrence After Radical Hepatectomy Using a Nomogram Model Based on the γ-Glutamyl Transpeptidase-to-Albumin Ratio.

BACKGROUND AND PURPOSE: The present study aimed to establish a γ-glutamyl transpeptidase-to-albumin ratio (GAR)-based nomogram model to predict early recurrence of hepatocellular carcinoma (HCC) after radical surgery. METHODS: Patients enrolled in this study were randomly allocated into a train and validation cohort in a ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) proportional hazards model and cox regression model were combined to identify independent risk factors related to HCC recurrence. Based on these risk factors, a predictive nomogram was constructed and validated in both inner and outer test cohorts. The performance of the nomogram was evaluated by C-index, the area under the receiver operating characteristic curve (AUC), the calibration curve and decision curve analysis. RESULTS: The tumor size, tumor number, BCLC stage, microvascular invasion (MVI) and GAR value were identified as independent risk factors related to HCC recurrence and used to construct the predictive nomogram. AUC of the nomogram showed satisfactory accuracy in predicting 1-, 3- and 5-year disease-free survival. The calibration curve showed agreement between the ideal and predicted values. The risk score more than 72 as calculated by the nomogram was related to early recurrence of HCC after radical surgery. DCA plots showed better clinical usability of the nomogram as compared with the BCLC staging system in all three included cohorts. CONCLUSION: The nomogram based on the GAR value may provide a new option for screening of the target HCC cohort of patients who need anti-recurrence therapy after surgery.

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model.

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

Integrated Bioinformatics Analysis and Validation of the Prognostic Value of RBM10 Expression in Hepatocellular Carcinoma.

Background: RBM10's function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study. Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein-protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test. Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1. Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.

Synthesis and antihistamine evaluations of novel loratadine analogues.

A series of loratadine analogues containing hydroxyl group and chiral center were synthesized. The effect of the synthesized compounds on the histamine-induced contractions of guinea-pig ileum muscles was studied. In addition, the in vivo asthma-relieving effect of the analogues in the histamine induced asthmatic reaction in guinea-pigs was determined. Most of the compounds exhibited definite H(1) antihistamine activity. The S-enantiomers, compounds 2, 4 and 8, are more potent than the R-enantiomers, compounds 1, 3 and 7. Compound 6 was the most active one among the eight synthesized compounds.

A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer.

To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell-derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene-annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80-gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five-gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five-gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five-gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC.

Dexamethasone decreases hepatocellular carcinoma cell sensitivity to cisplatin-induced apoptosis.

BACKGROUND/AIMS: Despite the fact that dexamethasone (DEX), a synthesized glucocorticoid (GCs), in vitro has pro-apoptotic effects on lymphoid cells, it has been suggested to induce apoptosis resistance toward chemotherapy in lung, cervical and breast cancer cell lines. However, the mechanisms by which GCs inhibit apoptosis in some cells have not been elucidated. The aim of this study is to investigate the effect of DEX on cisplatin (CIS)-induced hepatocellular carcinoma cell proliferation, apoptosis and to determine apoptosis-related gene expression on mRNA and protein levels. METHODOLOGY: MTT assay, annexin V-FITC as well as Hoechst33258 staining were performed to detect hepatocellular carcinoma cell proliferation and apoptosis, respectively. RT-PCR and western blot were used to determine Bcl-2 and Bcl-xL expression. RESULTS: DEX alone did not cause any obvious change to HepG2 and SNU449 cell proliferation. When pretreated with DEX followed by CIS treatment, cells showed resistance to CIS-induced cytotoxicity by MTT assay and apoptosis detected by Annexin V-FITC kit double staining. Hoechst33258 staining showed that CIS caused cell nuclear condensation, a sign of apoptosis and DEX pretreatment reduced the proportion of apoptotic cells. Anti-apoptotic genes Bcl-2 and Bcl-xL expression levels decreased after CIS treatment, but increased again after DEX addition. CONCLUSIONS: DEX can decrease hepatocellular carcinoma cell sensitivity to CIS-induced cell death by preventing cell apoptosis.

Composition analysis of colored dissolved organic matter in Taihu Lake based on three dimension excitation-emission fluorescence matrix and PARAFAC model, and the potential application in water quality monitoring.

Taihu Lake is one of the five biggest lakes in China. Surface water samples from 26 sampling sites of Taihu Lake were collected. Furthermore wet chemical analysis (COD(Cr) and BOD5) and measurement of three dimensional excitation-emission matrix (3DEEM) spectra in the laboratory have been conducted. Using parallel factor analysis (PARAFAC) model, three components of colored dissolved organic matter (CDOM) have been identified successfully, based on the analysis of 3DEEM data. The characteristics of the three components also have been described by comparing them to some components of CDOM, identified in earlier researches. Meanwhile, spatial variations of concentration for the three components in Taihu Lake have been analyzed, and the result indicates that the concentration of component 1 depends more on the situation of wastewater pollution and can be used as the indicator of wastewater pollution. The relationship between the concentrations of the three components and results of the wet chemical analysis show that none of the three components can be used as indicators of gross organic matter in water. However, the concentrations of all the three components have obvious linear relationships with the BOD5 value, especially for component 1 (r = 0.72878). Finally, the potential applications of the composition analysis based on 3DEEM and PARAFAC model in water quality monitoring have been illuminated.

Association of ADAM33 gene polymorphisms with asthma in the Uygur population of China.

Asthma is one of the most common chronic respiratory diseases, affecting ∼300 million children and adults worldwide. Previous studies identified a disintegrin and metalloprotease domain 33 (ADAM33) as an important susceptibility gene for asthma in patients of different nationalities; however, it is unknown whether this relationship exists in ethnically diverse populations. The present study focused on the association between single-nucleotide polymorphisms (SNPs) of the ADAM33 gene and asthma in the Uygur population of China. Three SNPs of ADAM33 (T1, S+1 and F+1) were genotyped in a case-control study among the Chinese Uygur population, involving 126 adult asthmatic patients and 126 healthy controls. The frequency of the ADAM33 T1 C allele among asthma patients was significantly higher compared to healthy controls (20.6 vs. 11.1%, P=0.003). The distribution of ADAM33 genotypes differed significantly between the two groups. The frequency of the T1 TC genotype was higher among patients compared to healthy controls [odds ratio (OR)=2.118, P=0.016] and the variant genotype, TC+CC, increased the risk of asthma (OR=2.244, P=0.005). Following adjustment for confounding factors, the ORs of TC and TC+CC for asthma were 2.317 and 2.522, respectively. There was a significant decrease in the forced expiratory volume (FEV1) levels in patients with the TC genotype compared to the TT genotype of T1. Haplotype analysis revealed that the frequencies of Hap5 (CAC) and Hap6 (CAT) were significantly higher among asthmatic patients compared to healthy controls (P=0.024 and 0.016, respectively). The genotype and allele frequencies of SNP S+1 and F+1 were not statistically different between asthmatic patients and controls. In conclusion, the ADAM33 T1 SNP may affect susceptibility to asthma in the Chinese Uygur population.

Porcine partial liver transplantation without veno-venous bypass: an effective model for small-for-size liver graft injury.

OBJECTIVE: Partial liver transplantation is currently gaining wider acceptance, which alleviates donor organ shortage, but also reveals the problem of small-for-size (SFS) syndrome. The precise mechanism behind it remains unknown. Large animal models for SFS syndrome are being developed using veno-venous bypass (VVB), however, splenectomies have often become necessary making the models useless for clinical situations. This study establishes a clinically well-simulated and effective model of SFS graft injury without VVB. METHODS: In this study, 30% and 100% of liver grafts were orthotopically transplanted to pigs in groups A (n = 12) and B (n = 5), respectively, both without VVB. Intraoperative hemodynamics and metabolic parameters were assessed consecutively. The operative survival rates were evaluated during 7 days of follow-up as well as the serum biochemical profiles, the kinesis of portal pressure gradient, and the pathological findings. RESULTS: All the recipients survived the anhepatic period except one in group A who died of irretrievable acidosis. The tolerance rate for non-VVB were 91.7% (11/12) in group A and 100% (5/5) in group B with no significant differences. The 7-day survival rate in group A was significantly less than that for group B (50% versus 100%, P < .05) with more prolonged prothrombin times, increased bilirubin and alanine aminotransferase levels, and persistantly higher values of portal pressure gradient during almost the entire follow-up period. Accordingly, the pathological findings clarified more severe microvascular impairments in group A than group B. CONCLUSION: These data suggest that the model of pigs transplanting with 30% liver grafts without VVB is safe and reproducible. The good clinical simulation on operative procedures and clinicopathological performance indicates it is a more rational model for further research on SFS syndrome.

Hepatic artery thrombosis after liver transplantation: three case reports.

OBJECTIVE: To explore the surgical techniques of hepatic artery reconstruction in liver transplantation (OLT) and the choice of treatment for hepatic artery thrombosis (HAT). METHODS: We analyzed hepatic artery reconstructions based on 234 cadaveric donor liver transplantations and seven living related liver transplantations from April 2003 to February 2009. Anastomosis time was compared between the groups with respect to vascular caliber. Interventional thrombolysis or early thrombectomy and hepatic artery reconstruction was implemented in three HAT cases. RESULTS: The hepatic artery anastomoses for vessels less than 3 mm in diameter (n = 78) required 33.6 ± 21.3 minutes which were significantly greater compared with those for vessels more than 3 mm in diameter (n = 163; 19.4 ± 7.4 minutes). Among two patients (0.83%) who developed early HAT within the first week after the operation, one was successfully treated by interventional thrombolysis, but the other required an urgent conduit between the aorta and the graft after attempted thrombolysis. Only one patient (0.41%) displayed a delayed HAT without special management, but recovered liver function upon follow-up. DISCUSSION: Early detection and proper revascularization measures can yield satisfactory results after HAT.