Inhibition of AGEs-RAGE-PP2A Axis Alleviates Cognitive Impairment after Chronic Heart Failure.

To investigate the effect of the AGEs-RAGE-PP2A axis on cognitive impairment (CI) after chronic heart failure (CHF). Mice were divided into six groups: Sham, TAC, Sham+RAGE-/-, TAC+RAGE-/-, AG, and FTY720 group. AG mice and FTY720 mice were treated with AGEs inhibitor (aminoguanidine, AG) and PP2A activator (FTY720) respectively after TAC surgery. The cardiac function of AG and TAC+RAGE-/- mice was significantly better than that of TAC mice (P<0.05). However, the heart function of FTY720 mice were just improved a part of that. To behavioral function, the escape latency period of the TAC+RAGE-/-, AG and FTY720 mice were significantly shorter (P<0.05), and the times of platform crossings and residence time of them were significantly improved (P<0.05). HE staining and silver staining show the structure of TAC+RAGE-/-, AG and FTY720 mice were more complete. Also, in these three groups, the expression of Aß and p-tau protein in the brain can be significantly down-regulated (P<0.05) and the PP2A protein expression level was up-regulated (P<0.05). And the expression of hippocampal Bax, Cyt-C, and Caspase-3 of that were all down-regulated (P<0.05), and Bcl-2 was up-regulated (P<0.05). Deficient of AGEs, RAGE and activating PP2A can significantly attenuate the cognitive impairment in CHF mice, and protect the brain structure. This mechanism seems via reducing the expression of Aß, p-tau, and apoptotic protein.

Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms?

Neoplasms are one of the most concerned public health problems worldwide. Digestive system neoplasms, with a high morbidity and mortality, is one of the most common malignant tumors in human being. It is found that exosomes act as an intercellular communication media to carry the metabolic and genetic information of parental cells to target cells. Likely, exosomes participate in lipid metabolism and regulates multiple processes in digestive system neoplasms, including the information transmission among cancer cells, the formation of neoplastic microenvironment, and the neoplastic biological behaviors like metastasis, invasion, and the chemotherapy resistance. In this review, we firstly introduce the main mechanisms whereas exosomes act as intercellular lipometabolic communication mediator in digestive system neoplasms. Thereafter we introduce the relationship between exosomes lipid metabolism and various type of digestive system neoplasms, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Eventually, we summarized and prospected the development and implication of exosomes in digestive system neoplasms. The further research of exosomes as intercellular lipid metabolism mediator will contribute to accurate and efficient diagnosis and treatment of digestive system neoplasms.

Lycopene alleviates oxidative stress-induced cell injury in human vascular endothelial cells by encouraging the SIRT1/Nrf2/HO-1 pathway.

BACKGROUND AND OBJECTIVE: Epidemiological research have displayed that dietary intake rich in lycopene, an antioxidant, is negatively correlated with the risk of cardiovascular disease (CVD). This study aimed to investigate whether the intervention with different concentrations of lycopene could attenuate H2O2-induced oxidative stress injury in human vascular endothelial cells (VECs). METHODS: The human VECs HMEC-1 and ECV-304 were incubated with a final concentration of 300 µmol/L H2O2, followed by they were incubated with lycopene at doses of 0.5, 1, or 2 µm. Subsequently, cell proliferation, cytotoxicity, cell adhesion, reactive oxygen species (ROS) contents, adhesion molecule expression, oxidative stress levels, pro-inflammatory factor production, the apoptosis protein levels, and the silent information regulator-1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway protein levels were tested by CCK-8 kit, lactate dehydrogenase (LDH) kit, immunofluorescence labeling, cell surface enzyme immunoassays (EIA), enzyme-linked immunosorbent assay (ELISA), as well as Western blot assays, respectively. RESULTS: Under H2O2 stimulation, HMEC-1 and ECV-304 cell proliferation and the SIRT1/Nrf2/HO-1 pathway protein expression were significantly reduced, whereas cytotoxicity, apoptosis, cell adhesion molecule expression, pro-inflammatory and oxidative stress factors production were apparently encouraged, which were partially countered by lycopene intervention in a dose-dependent manner. CONCLUSION: Lycopene alleviates H2O2-induced oxidative damage in human VECs by reducing intracellular ROS levels, inflammatory factor production, cell adhesiveness, and apoptosis rate under oxidative stress conditions through activation of the SIRT1/Nrf2/HO-1 pathway.

Hedgehog signaling-related genomics signature for the accurate progress and prognosis prediction in gastric cancer.

The Hedgehog pathway is thought to be closely associated with the progression of GC; however, a specific link between the Hedgehog pathway on the prognosis and immune infiltration of gastric cancer is still lacking. This study collected Hedgehog pathway-related genes. The Hedgehog pathway-related pattern were identified by consensus cluster analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the biological functions which were significantly altered between predefined Cluster1 and Cluster2 in consensus clustering. The risk model of gastric cancer based on Hedgehog signaling pathway was constructed by univariate and multivariate COX regression, and the nomogram was constructed. The results showed that there were significant differences in the expression of Hedgehog pathway-related genes between the two groups. In addition, the constructed risk model was significantly correlated with the clinical prognosis and immune cell infiltration level of patients with gastric cancer. The model effectively predicted the efficacy of chemotherapy in GC patients and the sensitivity of drug treatment between groups. We systematically revealed the mechanism of Hedgehog pathway in gastric cancer and selected biomarkers with biological significance from a new perspective, providing potential direction for the treatment of gastric cancer.

The relation of blood cell division control protein 42 level with disease risk, comorbidity, tumor features/markers, and prognosis in colorectal cancer patients.

BACKGROUND: Cell division control protein 42 (CDC42) is involved in colorectal cancer (CRC) progression by modulating CD8+ T cell activation, immune escape, and direct oncogenetic biological processes. This study aimed to explore the correlation of blood CDC42 with disease risk, comorbidities, disease features, tumor markers, and prognosis among CRC patients. METHODS: CDC42 in peripheral blood mononuclear cells was detected by reverse transcription-quantitative polymerase chain reaction from 250 resectable CRC patients and 50 healthy controls (HCs). CDC42 was divided by quartiles, as well as high and low expressions in CRC patients for correlation and survival analysis. RESULTS: CDC42 was elevated in CRC patients vs. HCs (p < 0.001), which had a good ability to distinguish CRC patients from HCs with the area under the curve (95% confidence interval) of 0.889 (0.841-0.937). In CRC patients, CDC42 was not associated with demographics or comorbidities (all p > 0.05), while its higher quartile was linked to increased T stage (p < 0.001), N stage (p = 0.009), TNM stage (p < 0.001), abnormal carcinoembryonic antigen (p = 0.043), and adjuvant chemotherapy administration (p = 0.002). Higher CDC42 quartile (p = 0.002) and CDC42 high (vs. low) (p < 0.001) were related to worse disease-free survival (DFS); meanwhile, elevated CDC42 quartile (p = 0.002) and CDC42 high (vs. low) (p = 0.001) were also linked to poor overall survival (OS). Multivariate Cox's regression analysis presented that CDC42 quartile 3 and 4 (vs. quartile 1) independently predicted declined DFS and OS (all p < 0.05). CONCLUSION: Circulating CDC42 relates to higher disease risk, T, N, and TNM stage, abnormal tumor marker, and poor prognosis among CRC patients.

The Efficacy of Senna Bowel Preparation for Colonoscopy: A Systematic Review and Meta-analysis.

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

Quadratus Lumborum Block is an Effective Postoperative Analgesic Technique in Pediatric Patients Undergoing Lower Abdominal Surgery: A Meta-Analysis.

BACKGROUND: Quadratus lumborum (QL) block has shown promising analgesic efficacy in the adult population in previous meta-analyses. However, the response of the pediatric group to pain stimulation is stronger than that in the adult population, and the management of pediatric pain is constrained by limited available analgesia agents. All data analyzed during this study are collected from published articles. OBJECTIVE: The purpose of our systematic review was to evaluate whether QL block is also an effective postoperative analgesic technique, compared to other analgesic skills in pediatric patients undergoing lower abdominal surgery. STUDY DESIGN: A meta-analysis. METHODS: We identified randomized controlled trials (RCTs) from PubMed, Embase, the Cochrane Library, Web of Science, and Science Direct to compare QL block with other analgesic methods for relief of postoperative pain in pediatric patients undergoing lower abdominal surgeries under general anesthesia. The primary outcome was the rate of postoperative rescue analgesia; secondary outcomes include: pain scores at 30 minutes and 1, 2, 4, 6, 12, and 24 hours postoperatively, patient satisfaction, and block related complications. RESULTS: A total of 7 studies with 346 patients were included. QL block showed a significant reduction in the rate of postoperative rescue analgesia in the first 24 hours (RR = 0.41; 95% CI = 0.28 to 0.59; P < 0.001) compared to other analgesic techniques, without significant heterogeneity among the articles (I2 = 49%, P = 0.08). Compared with other analgesic methods, QL block significantly reduced the pain scores at 2 hours (Std.MD = -0.76; 95% CI = -1.16 to -0.35; P < 0.001) (I2 < 0.001%, P = 0.41), 4 hours (Std.MD = -0.34; 95% CI = -0.67 to -0.01; P = 0.04) (I2 < 0.001%, P = 0.53) and 12 hours postoperatively (Std.MD = -0.95; 95% CI = -1.44 to -0.47; P < 0.001) (I2 = 27%, P = 0.24). No significant differences were found between techniques at 30 minutes and 1, 6, or 24 hours postoperatively (P > 0.05). There was no statistically significant change in patient satisfaction (Std.MD = 0.49; 95% CI = -0.32 to 1.29; P = 0.24) or side effects (RD = -0.02; 95% CI = -0.06 to 0.02; P = 0.31) with QL block. LIMITATIONS: The major limitation of this meta-analysis is the relatively few RCTs and limited results included. Similarly, the differences in block approaches among the control groups (TAP, ESP, caudal block, opioid-based analgesia), drug types and concentrations, and multimodal analgesia programs led to considerable heterogeneity. Furthermore, some relevant outcomes were not investigated. CONCLUSION: Our systematic review and meta-analysis suggests QL block use for the pediatric population undergoing lower abdominal surgery, based on the current limited research evidence, as this method was an effective postoperative analgesic technique.

Predictive value of baseline 18F-FDG PET/CT and interim treatment response for the prognosis of patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy.

The present study aimed to investigate the prognostic value of baseline 18F-FDG PET/CT quantitative parameters and interim treatment response, and to assess whether the combination of these could improve the predictive efficacy in patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. PET/CT images and clinical data of 64 patients with DLBCL who had undergone 18F-FDG PET/CT scan before and after 3 or 4 cycles of R-CHOP chemotherapy were retrospectively reviewed. The quantitative parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter of the maximum lesion (Dmax) were measured on baseline PET/CT images. Cox proportional hazards model was used to evaluate the influence of baseline PET/CT parameters, clinical indicators and interim treatment response on prognosis. Survival analysis was performed using Kaplan-Meier method. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive efficacy of the combination of baseline PET/CT parameters and interim treatment response. Ann Arbor stage, International Prognostic Index (IPI), lactate dehydrogenase (LDH), necrosis, MTVmax, TLGmax, Dmax and interim treatment response showed association with 2-year progression-free survival (PFS, P<0.05). LDH, necrosis, MTVmax, MTVsum, TLGmax, TLGsum, Dmax and interim treatment response showed association with 2-year overall survival (OS, P<0.05). Ann Arbor stage, Dmax and interim treatment response were found to be independent predictors of 2-year PFS (P<0.05), while Dmax and interim treatment response were found to be independent predictors of 2-year OS (P<0.05). The PFS and OS curves of Dmax <5.7 cm group and Dmax ≥5.7 cm group, complete response (CR) group and non-CR group were significantly different, respectively (P<0.05). The baseline 18F-FDG PET/CT parameters and interim treatment response have important prognostic values in DLBCL patients who received R-CHOP chemotherapy. Combined application of Dmax and interim treatment response improved the predictive efficacy of 2-year PFS. It may be helpful to identify patients who are at high-risk of relapse and to guide early clinical intervention of these patients.

Neuronal intranuclear inclusion disease: two case report and literature review.

Neuronal intranuclear inclusion disease (NIID) is a rare and slowly progressing neurodegenerative disease characterized by the presence of eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. Sporadic NIID case was more frequently encountered than familial. In our study, we reported two adult-onset NIID patients from a family and described their clinical, imaging, and pathological features. The first patient was a 61-year-old man who only presented with non-specific headache and dizziness; however, Brain MRI with diffusion-weighted images (DWI) sequence showed high-intensity signal involving a small regional portion of corticomedullary junction in the frontal and parietal lobe. The older sister of former, a 64-year-old female, who developed sudden onset of weakness of the right limb was admitted to our neurology department. Compared with the first patient, similar DWI high-intensity signal but more extensive area in the corticomedullary junction was found in her brain MRI examination, also prominent leukoencephalopathy in T2-weighted image. Significantly, skin pathology of the first patient showed that typical inclusions with strongly positive P62 and ubiquitin antibody could be seen in the nuclei of sweat gland cells, adipocytes, and fibroblasts. FMR1 gene was negative. Although rare, adult-onset NIID should be considered when the characteristic radiology changes of high intensity signal involving the corticomedullary junction in the brain DWI sequence was found. In addition, the pathological result of skin biopsy combined with negative genetic testing FMR1 or NOTCH2NLC can contribute to the accurate diagnosis of the disease. This article aims to improve the radiologists' knowledge of NIID by our cases presentation and reviewing literature.

Optimal Laparoscopic Management and Oncological Outcomes of Gastrointestinal Stromal Tumors in Duodenum: Pancreaticoduodenectomy or Pancreas-Sparing Duodenectomy?

BACKGROUND: Gastrointestinal stromal tumors (GIST) of the duodenum are rarely reported and optimal minimally invasive management has not been well proposed. Pancreaticoduodenectomy and different types of pancreas-sparing duodenectomy can be chosen; however, which to choose and its corresponding clinical outcomes and oncological concerns remain controversial. PATIENTS AND METHODS: Patients diagnosed with GIST of duodenum underwent laparoscopic pancreaticoduodenectomy (L-PD) or pancreas-sparing duodenectomy (L-PSD) in Zhejiang Provincial People's Hospital were enrolled. All prospectively maintained data were analyzed retrospectively. Patients were grouped into the L-PD group or the L-PSD group, and the clinical outcomes and oncological outcomes were analyzed. RESULTS: Between June 2013 and March 2019, a total of 22 patients (11 males/11 females) underwent surgical management, including 13 L-PDs and 9 L-PSDs. The average age was 58.2±9.5 year-old (median 60.5 year-old). The most common presentations were GI bleeding (54.5%) and abdominal discomfort (27.2%), and the dominant lesion located in the second portion of duodenum (59.1%). Compared with L-PD group, L-PSD group showed much shorter operation time (364.2±58.7min vs. 230.0±12.3min, P<0.001), less blood loss (176.9±85.7mL vs. 61.1±18.2min, P<0.001), faster recovery to off-bed (2.6±1.3d vs. 1.1±0.3d, P=0.003), anus flatus (4.5±1.0d vs. 2.4±0.5d, P<0.001) and liquid intake (4.9±1.3d vs. 2.3±0.5d, P<0.001). Lymph node retrieval was much less in L-PSD, but no lymph node metastasis was observed in any patients. L-PSD had much Lower morbidity of both minor (Grade I/II) and major (III/IV/V) complications than that of L-PD (11.1% vs. 61.6%, P=0.02), resulting in shorter hospital stays (10.9±3.8d vs. 20.6±11.1d, P=0.021) and less total cost (76,972.4±11,614.8yuan vs 125,628.7±46,356.8yuan, P=0.006). The median follow-up was 42 months (range from 12 to 82months) without loss. Only 1 L-PD patient suffered hepatic metastasis 36months after surgery, and given sunitinib to stabilize the disease, none of the rest observed recurrence or metastasis. CONCLUSION: For GIST located opposite the major papilla, L-PSD showed comparable safety and oncological benefits when compared to L-PD, with shorter operation time, less blood loss and much faster recovery time, resulting in much less total cost. L-PSD should be applied in selected patients with experienced hands.

Two ZnII-based MOFs constructed with biphenyl-2,2',5,5'-tetracarboxylic acid and flexible N-donor ligands: syntheses, structures and properties.

Two new Zn2+-based metal-organic frameworks (MOFs) based on biphenyl-2,2',5,5'-tetracarboxylic acid, i.e. H4(o,m-bpta), and N-donor ligands, namely, poly[[(µ4-biphenyl-2,2',5,5'-tetracarboxylato)bis{[1,3-phenylenebis(methylene)]bis(1H-imidazole)}dizinc(II)] dimethylformamide monosolvate dihydrate], {[Zn2(C16H6O8)(C14H14N4)2]·C3H7NO·2H2O}n or {[Zn2(o,m-bpta)(1,3-bimb)2]·C3H7NO·2H2O}n (1) {1,3-bimb = [1,3-phenylenebis(methylene)]bis(1H-imidazole)}, and poly[[(µ4-biphenyl-2,2',5,5'-tetracarboxylato)bis{[1,4-phenylenebis(methylene)]bis(1H-imidazole)}dizinc(II)] monohydrate], {[Zn2(C16H6O8)(C14H14N4)2]·H2O}n or {[Zn2(o,m-bpta)(1,4-bimb)2]·H2O}n (2) {1,4-bimb = [1,4-phenylenebis(methylene)]bis(1H-imidazole)}, have been synthesized under solvothermal conditions. The complexes were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction and powder X-ray diffraction analysis. Structurally, the (o,m-bpta)4- ligands are fully deprotonated and combine with Zn2+ ions in µ4-coordination modes. Complex 1 is a (3,4)-connected porous network with honeycomb-like [Zn2(o,m-bpta)]n sheets formed by 4-connected (o,m-bpta)4- ligands. Complex 2 exhibits a (2,4)-connected network formed by 4-connected (o,m-bpta)4- ligands linking Zn2+ ions in left-handed helical chains. The cis-configured 1,3-bimb and 1,4-bimb ligands bridge Zn2+ ions to form multi-membered [Zn2(bimb)2] loops. Optically, the complexes show strong fluorescence and display larger red shifts compared to free H4(o,m-bpta). Complex 2 shows ferroelectric properties due to crystallizing in the C2v polar point group.

Combined hepatocellular-cholangiocarcinoma: which preoperative clinical data and conventional MRI characteristics have value for the prediction of microvascular invasion and clinical significance?

OBJECTIVES: To explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have clinical significance. METHODS: The study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group [n = 56], MVI-negative group [n = 57]). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan-Meier survival curves and compared using the log-rank test. RESULTS: The majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282-0.971; p = 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749-75.098; p = 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164-0.631; p = 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio [HR], 0.402; 95% CI, 0.189-0.854, p = 0.013). CONCLUSION: A higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI. KEY POINTS: • Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor. • cHCC-CCA with MVI may have a higher risk of early recurrence after surgery. • Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.

The Predictive Value of Pre-/Postneoadjuvant Chemoradiotherapy MRI Characteristics for Patient Outcomes in Locally Advanced Rectal Cancer.

RATIONALE AND OBJECTIVES: This study aimed to investigate the predictive value of pre-/postneoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) characteristics for the long-term survival outcomes in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: We retrospectively evaluated pre- and post-nCRT MRI and clinicopathologic characteristics of LARC patients. The 3-year disease-free survival (DFS) was estimated using the Kaplan-Meier product-limit method. Associations between MRI variabilities and survival outcomes were assessed using Cox proportional hazards model. RESULTS: In total, 171 LARC patients (112 men and 59 women) with a median age of 55 years (range, 27-82 years) treated with nCRT were evaluated. The median follow-up was 47.6 months, and the 3-, 4-, and 5-year DFS in the overall cohort was 76.6%, 74.5%, and 73.7%, respectively. MRI assessment of extramural venous invasion (mrEMVI) positivity was a significant independent adverse factor of long-term survival (hazard ratio [HR] = 2.589, 95% confidence interval [CI] = 1.398-4.794, p = 0.002) on multivariate analysis. Patients with positive mrEMVI had significantly lower 3-year DFS than those with negative mrEMVI (52.6 months vs 65.1 months; p = 0.003). Moreover, the tumor regression grade on MRI (mrTRG) also significantly correlated with survival outcomes in patients with LARC. Patients with partial response on post-nCRT MRI (mrPR) showed short DFS than those with complete response (mrCR; HR = 4.914, 95% CI = 1.176-20.533, p = 0.029). The 3-year DFS of mrCR and mrPR patients were 74.3 months and 58.9 months, respectively (p = 0.011). CONCLUSION: The pre-/post-nCRT MRI characteristics may be used to long-term survival stratification in LARC patients. mrEMVI positivity was an independent adverse prognostic indicator for 3-year DFS. Further, mrTRG may also be a predictive factor for the prognosis of LARC patients. The pre-/post-nCRT MR imaging may offer more information for providing individualized treatment.

Potent and selective PTP1B inhibition by a platinum(ii) complex: possible implications for a new antitumor strategy.

Showing anti-proliferation activity against MCF7 cells better than cisplatin, a platinum(ii) complex, [PtL(DMSO)Cl], was found to potently and selectively inhibit protein tyrosine phosphatase 1B (PTP1B), a putative target for anticancer agents, suggesting a new possible anticancer strategy based on platinum drugs.

Identification of key pathways and biomarkers in sorafenib-resistant hepatocellular carcinoma using bioinformatics analysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant types of cancer, with a high mortality rate. Sorafenib is the sole approved oral clinical therapy against advanced HCC. However, individual patients exhibit varying responses to sorafenib and the development of sorafenib resistance has been a new challenge for its clinical efficacy. The current study identified gene biomarkers and key pathways in sorafenib-resistant HCC using bioinformatics analysis. Gene dataset GSE73571 was obtained from the Gene Expression Omnibus (GEO) database, including four sorafenib-acquired resistant and three sorafenib-sensitive HCC phenotypes. Differentially expressed genes (DEGs) were identified using the web tool GEO2R. Functional and pathway enrichment of DEGs were analyzed using the Database for Annotation, Visualization and Integrated Discovery and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. A total of 1,319 DEGs were selected, which included 593 upregulated and 726 downregulated genes. Functional and pathway enrichment analysis revealed DEGs enriched in negative regulation of endopeptidase activity, cholesterol homeostasis, DNA replication and repair, coagulation cascades, insulin resistance, RNA transport, cell cycle and others. Eight hub genes, including kininogen 1, vascular cell adhesion molecule 1, apolipoprotein C3, alpha 2-HS glycoprotein, erb-b2 receptor tyrosine kinase 2, secreted protein acidic and cysteine rich, vitronectin and vimentin were identified from the PPI network. In conclusion, the present study identified DEGs and key genes in sorafenib-resistant HCC, which further the knowledge of potential mechanisms in the development of sorafenib resistance and may provide potential targets for early diagnosis and new treatments for sorafenib-resistant HCC.

Bioconcentration and Metabolism of Emodin in Zebrafish Eleutheroembryos.

Emodin is a major active anthraquinone of various herbal laxatives, which can exert many pharmacological effects. However, chronic use of anthranoid laxatives, even at low dosages, may cause melanosis coli (MC). It has been suggested that the accumulation of anthraquinones is a risk factor in the MC process. To investigate the accumulation of emodin, we conducted a bioconcentration study of emodin in zebrafish eleutheroembryos. Based on the economic cooperation and development (OECD) 305 test, zebrafish eleutheroembryos were exposed to emodin at a constant concentration for 48 h, before the test media were replaced by the blank medium for 24 h of depuration. To eliminate the effect of metabolism of emodin for assessment of the bioconcentration factor (BCF), we also conducted a modified test for which zebrafish eleutheroembryos were exposed to the non-renewed test media, whose emodin concentration decreased with time. At different exposure time points, zebrafish eleutheroembryos and exposure media were sampled for analysis of emodin concentration using HPLC-MS/MS. The results showed rapid accumulation of emodin in zebrafish eleutheroembryos to reach a steady-state concentration within 24 h. Meanwhile, emodin was actively metabolized by zebrafish eleutheroembryos to result in 29.5-40.7% of its elimination. In the groups with high or low concentrations of emodin, the standardized BCF (sBCF) values in the standard test were 24.0 and 20.0, while those in the modified test were 50.4 and 52.0. These results showed that emodin could accumulate in zebrafish eleutheroembryos when used for 48 h and beyond, suggesting that the accumulation of anthraquinones may be a risk factor in the MC process. Accordingly, emodin should be unsuitable for long-term use due to its accumulation.

Comparison of 3.0T MRI with 3D LAVA sequence and digital subtraction angiography for the assessment of accessory hepatic veins in Budd-Chiari syndrome.

PURPOSE: To compare 3D liver acceleration volume acquisition (LAVA) and digital subtraction angiography (DSA) for evaluating the presence of accessory hepatic veins (AHV) in Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: This was a retrospective study in 228 patients with BCS who underwent 3.0T magnetic resonance imaging (MRI) with the 3D LAVA sequence. Two reviewers noted AHV: openings located in the inferior vena cava (IVC), caliber, and the angle of entering into the IVC. MRI results were compared to DSA. Kappa statistics were calculated to quantify intrareader variability in detecting AHVs. RESULTS: On MRI, 63 patients demonstrated no AHV on LAVA images, 70 had one AHV, 62 had two AHVs, 26 patients had three AHVs, six patients had four AHVs, and one patient had five AHVs (P < 0.05 vs. DSA). The mean caliber of the AHVs was 8.3 ± 4.0 mm compared to 9.9 ± 3.2 for DSA (P < 0.001). Among the 301 AHVs, there were 140 with acute angles (46.5%), 71 with right angles (23.6%), and 90 with obtuse angles (29.8%). The prevalence of AHVs on DSA was 54.8% (125/228), while MRI demonstrated 301 AHVs in 165 patients, for a prevalence of 72.4% (165/228) compared to 54.8% for DSA (P = 0.001). The two methods were concordant in only 116/228 (50.9%) patients. The kappa coefficient demonstrated good intrareader consistency for all documented MRI findings of AHVs (κ = 0.626 for caliber and κ = 0.65 for angles). CONCLUSION: More AHVs were visible on MRI LAVA sequences than on conventional DSA. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:401-409.

Temporal Features of the Differentiation between Self-Name and Religious Leader Name among Christians: An ERP Study.

Existing neuroimaging studies have shown that religion, as a subjective culture, can influence self-referential processing. However, the time course of this impact remains unclear. The present study examined how Christians process their own names, the name of their religious leader (i.e., Jesus), and a famous person's name (i.e., Yao Ming). Behavioral and EEG data were recorded while the participants performed a name-color judgment task for these three names. The behavioral data showed no significant differences in reaction time or accuracy among the names. However, the ERP data showed that the P200 and P300 amplitudes elicited by the self-name and religious leader name were larger than those elicited by the famous name. Furthermore, the self-name also elicited a larger P300 amplitude than the religious leader name did. These results suggested that both the self-name and the religious leader name were processed preferentially due to their important social value for the self as compared to a generally famous name. Importantly, the dissociation between the self-name and the religious leader name was observed at a high-order cognitive stage, which might be attributed to their different roles in one's self-concept.