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The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC, si-GAS5, si-PTEN or si-Ctrl. A human liver cancer cell line (SMCC-7721) was incubated with the modified TAM supernatant. Quantitative real-time PCR and Western blot were performed to detect gene and protein expression. The cell proliferation and invasion properties of the SMCC-7721 cells were detected by MTT and Transwell assays. GAS5 is up-regulated in M1 macrophages and down-regulated in M2 macrophages and TAMs. GAS5 overexpression promoted M1-like polarization of TAMs and inhibited M2-like polarization of TAMs. Moreover, GAS5 promoted the expression of PTEN in TAMs. PTEN-silenced TAM supernatant treatment promoted cell proliferative and invasive properties of the SMCC-7721 cells and diminished the effect of GAS5-overexpressed TAM supernatant on the cell proliferation and invasion by SMCC-7721 cells. Our results demostrared that GAS5 overexpression inhibited M2-like polarization of TAMs by enhancing PTEN expression, thereby inhibiting cell proliferation and invasion by SMCC-7721 cells. Thus, our results suggest that GAS5 may be a new therapeutic target for HCC treatment., (© 2020 Company of the International Journal of Experimental Pathology (CIJEP).)

Subarachnoid hemorrhage (SAH) patients' surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rodent and human central nervous system (CNS). Previously, we showed that monoclonal antibodies that specifically block inhibitory RGMa signaling promote neuroprotective and regenerative effects when administered acutely in a clinically relevant rat model of thoracic SCI. However, it is unknown whether systemic administration of RGMa blocking antibodies are effective for SCI after delayed administration. Here, we administered elezanumab, a human monoclonal antibody targeting RGMa, intravenously either acutely or at 3 h or 24 h following thoracic clip impact-compression SCI. Rats treated with elezanumab acutely and at 3 h post-injury showed improvements in overground locomotion and fine motor function and gait. Rats treated 24 h post-SCI trended towards better recovery demonstrating significantly greater stride length and swing speed. Treated rats also showed greater tissue preservation with reduced lesion areas. As seen with acute treatment, delayed administration of elezanumab at 3 h post-SCI also increased perilesional neuronal sparing and serotonergic and corticospinal axonal plasticity. In addition, all elezanumab treated rats showed earlier spontaneous voiding ability and less post-trauma bladder wall hypertrophy. Together, our data demonstrate the therapeutic efficacy of delayed systemic administration of elezanumab in a rat model of SCI, and uncovers a new role for RGMa inhibition in bladder recovery following SCI., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Background: The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP)., Methods: We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed., Results: In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P < 0.05). The frequency of surgical intervention and hospitalization time in patients with NP complicated with extrapancreatic infection was greatly increased (P < 0.05). Regarding the primary outcome, patients in the combined infection group had longer hospital stays (68.28 ± 51.80 vs 55.58 ± 36.24, P < 0.05) and higher mortality (24.0% vs 9.2%, P < 0.05) than patients in the pancreatic infection group. In addition, patients in the extrapancreatic infection group also showed high intensive care utilization (59.1%) and mortality rates (18.2%). Among the 137 AP patients with infection complications, 89 patients exhibited multidrug-resistant (MDR) microorganisms, and the mortality rate of patients with MDR bacterial infection was higher than that of patients with non-MDR bacterial infection (24.7% vs 3.6%, P = 0.001)., Conclusion: Clinicians should be aware that extrapancreatic infection (EPI) significantly aggravates the main outcome in pancreatic infection patients. Infection with MDR bacteria is also associated with AP mortality.

Propofol, a common intravenous anesthetic, has been found to exert anti-cancer effects with inhibition of cancer cell proliferation, migration and invasion. We tested its possible action against HER2-overexpressing breast cancer cells that developed resistance against trastuzumab. Cell viability assay, ELISA for cytokines, mammosphere formation, quantitative RT-PCR for EMT/IL-6-targeting miRNAs and the in vivo experimental pulmonary metastasis model were performed to understand the epigenetic action of propofol. Propofol sensitized HER2 overexpressing cells to trastuzumab but such action was even more pronounced in resistant cells. Increased cytokines IL-6 as well as IL-8 were released by resistant cells, along with increased mammospheres and induction of EMT, all of which was inhibited by propofol. IL-6 targeting tumor suppressor miR-149-5p was found to be the novel miRNA that was up-regulated by propofol, resulting in the observed effects on cell viability, IL-6 production, mammospheres generation as well as EMT induction. Further, antagonizing miR-149-5p attenuated the propofol effects confirming the epigenetic activity of propofol through miR-149-5p regulation. Finally, in vivo validation in an experimental metastasis model conformed an inhibitory action of propofol against experimental lung metastasis and the essential mechanistic role of miR-149-5p/IL-6 loop. These results present a novel role of general anesthetic propofol against resistant breast cancer cells and the underlying epigenetic regulation of a tumor suppressor miRNA.

Ketamine is gaining ground as a potential treating depression because it has a distinct mode of action than typical drugs that influence monoamine neurotransmitters including noradrenaline, dopamine, or serotonin. Ketamine is thought to act by blocking N-methyl-d-aspartate (NMDA) receptors in the brain, which interact with the amino acid neurotransmitter glutamate. The resultant chemical changes in the brain caused by ketamine are not yet fully understood but could involve ketamine-induced gene expression and signaling cascades that act long after the drug has been eliminated from the body. Despite these remarkable effects, the widespread use of ketamine is limited by potential side effects including the emergence reactions (hallucinations, dreams, and out-of-body experiences) by recreational users, who need further study before long-term use of ketamine can be approved for depression. Thus, studies are necessary to further elucidate mechanistic actions of ketamine at cellular and network levels. Thus, we are exploring the involvement of molecular targets for the treatment and psychomimetic phenomena of the ketamine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the feasibility, efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the individualized treatment of patients with refractory ascites and variceal hemorrhage caused by portal hypertension. Methods: Prospective study of clinical data of 47 patients with portal hypertension and refractory ascites and variceal bleeding admitted to the Affiliated Hospital of Xuzhou Medical University from August 2017 to December 2018, 26 males and 21 females, aged 23-75 (52±14) years old. The Viabahn stent was used to control the diameter of the shunt and the preoperative interval of PPG after individualized TIPS was determined according to the preoperative liver function Child-Pugh classification. The PPG of the Child A and B patients was <10 mm Hg (1 mmHg=0.133 kPa), Child-Pugh C grade patients with postoperative PPG interval values of 12 to 15 mmHg. The success rate, hemostasis rate, ascites remission rate, and complication rate were recorded. Results: Forty-seven patients were with a success rate of 100%, and there was no surgically related fatal complications. The portal pressure gradients of patients with Child-Pugh A, B and Child-Pugh C were reduced from preoperative (22.5±5.4), (24.4±2.6) mm Hg to postoperative (8.8±2.5), (13.2±1.1) mm Hg (all P< 0.05). All the patients were followed up for 6 to 24 months, with a median follow-up of 13 months. The success rate of hemostasis in patients with upper gastrointestinal bleeding was 93.5% (29/31), the remission rate of patients with refractory ascites was 14/16, the postoperative rebleeding rate was 6.5% (2/31), the incidence of hepatic encephalopathy was 8.5% (4/47), and the shunt disorder was 2.1% (1/47). Conclusion: The use of Viabahn stent for individualized TIPS in the treatment of portal hypertension with refractory ascites and variceal hemorrhage is feasible, and the clinical efficacy is affirmative, which can reduce the incidence of postoperative hepatic encephalopathy and shunt dysfunction.

Malignant hyperthermia is a pharmacogenetic disorder, which is an uncommon but frequently fatal intricacy of inhalation anesthesia in man. It causes a quick rise in body temperature to highly irreversible levels, which causes death in around three of four cases. The trigger anesthetics cause an anomalous, continued ascent in myoplasmic calcium levels. Possible mechanisms by which continuous release of sodium, calcium from skeletal muscle plasma membrane and sarcoplasmic reticulum stores respectively can produce the profound hyperthermia are discussed., (© 2019 International Union of Biochemistry and Molecular Biology.)

Interleukin-17A (IL-17A) and interleukin-17F (IL-17F) as two potent proinflammatory cytokines and the signature cytokines of Th17 cells play important roles in human autoimmune diseases, inflammation and host defenses. In this study, rhesus macaque IL-17A (rhIL-17A) and IL-17F (rhIL-17F) were cloned and expressed, and their biological activities and in vivo distribution were examined. The resulting data showed that both the rhIL-17A and rhIL-17F genes were consisted of three exons and two introns. RhIL-17A and rhIL-17F shared 96.8% and 93.9% amino acid sequence identity with human IL-17A (huIL-17A) and IL-17F (huIL-17F) respectively and the sequences also shared one N-glycosylation site and six conserved cysteine residues with huIL-17A and huIL-17F. IL-17A and IL-17F transcripts were highly expressed in lymphoid tissues and the intestinal tract of rhesus macaques. Functionally, recombinant rhIL-17A and rhIL-17F showed similar effect on Act1 levels and NF-κB phosphorylation compared with that of commercial human IL-17A and IL-17F. Moreover, the antibacterial proteins (such as β-defensin 2, S100A8, S100A9, RegIIIα and Muc1) and the tight junction associated genes (including CLDN1, CLDN4, OCLN, and ZO1) expressed by Caco-2 cells were largely enhanced after treatment with rhIL-17A and rhIL-17F. Meanwhile, purified rhIL-17A and rhIL-17F could also induce the expression of IL-6 and TNF-α by THP-1 cells. These data indicated that rhesus macaque IL-17A and IL-17F are highly similar to that of humans in both structure and function. Studies on rhIL-17A/rhIL-17F are promising approach to contribute to the understanding of human IL-17A and IL-17F-related intestinal diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

An efficient I 2 /CuCl 2 -promoted one-pot three-component strategy for the construction of 1,2,3-thiadiazoles from aliphatic- or aromatic-substituted methyl ketones, p-toluenesulfonyl hydrazide, and potassium thiocyanate has been developed. Simple and commercially available starting materials, a broad substrate scope, and excellent functional group tolerability make this strategy practical for applications. Furthermore, 1,2,3-thiadiazole synthesis was realized by using potassium thiocyanate as an odorless sulfur source.

Pristimerin, a triterpenoid isolated from Celastraceae and Hippocrateaceae, is known to induce cytotoxicity in several cancer cell lines. However, whether pristimerin can induce apoptosis in cholangiocarcinoma cells and the underlying mechanism remain unexplored. We assessed the function of human cholangiocarcinoma QBC and RBE cell lines using various experimental methods such as the cell viability assay to elucidate the viability of cells, flow cytometry to detect the death rate of cells, and Western blot analysis to evaluate the expression of cell cycle-related proteins and autophagy-related proteins. Human cholangiocarcinoma QBC cells were transplanted to nude mice to establish an animal model, and the effect of pristimerin on tumor growth in this model was observed. QBC and RBE cell lines treated with pristimerin (0, 5, 10, and 20 μmol/L) demonstrated the induction of apoptosis in a dose-dependent manner. The cell viability assay revealed a reduction in the cell viability with an increase in the pristimerin concentration. Similarly, flow cytometry revealed a gradual increase in the cell death rate with an increase in the pristimerin concentration. In addition, pristimerin significantly lowered the expression of apoptosis-related proteins (Bcl-2, Bcl-xL, and procaspase-3), but increased the Bax expression. Furthermore, pristimerin resulted in the G0/G1 cell-cycle arrest, reducing the expression of cell cycle-related proteins (cyclin E, CDK2, and CDK4), and increased the expression of autophagy-related proteins (LC3) in QBC cell line. Treatment with pristimerin could inhibit tumor growth in the nude mouse model. Overall, this study suggests the potential effect of pristimerin on the cell-cycle arrest and apoptosis in human cholangiocarcinoma cells., (© 2019 Wiley Periodicals, Inc.)

Rhesus macaques ( Macaca mulatta ) and cynomolgus macaques ( Macaca fascicularis ) are frequently used in establishing animal models for human diseases. To determine the differences in gut microbiota between these species, rectal swabs from 20 rhesus macaques and 21 cynomolgus macaques were collected, and the microbial composition was examined by deep sequencing of the 16S rRNA gene. We found that the rectal microbiota of cynomolgus macaques exhibited significantly higher alpha diversity than that of rhesus macaques, although the observed number of operational taxonomic units (OTUs) was almost the same. The dominant taxa at both the phylum and genus levels were similar between the two species, although the relative abundances of these dominant taxa were significantly different between them. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed significant differences in the functional components between the microbiota of the two species, in particular the lipopolysaccharide (LPS) synthesis proteins. The above data indicated significant differences in microbial composition and function between these two closely related macaque species, which should be taken into consideration in the future selection of these animals for disease models.

The aim of this study was to describe and assess the efficacy of a combination of multiple artery-first approaches (CMAFA) in pancreatoduodenectomy (PD) depending on the tumor location from an embryonic point of view.Between January 2011 and December 2016, seventy-nine consecutive patients with pancreatic head cancer (PHC) underwent PD with curative intent. Patients were classified into two groups according to the surgical procedure: CMAFA-PD group (n = 38) and conventional PD (Co-PD) group (n = 41). Clinicopathlogical variables and clinical outcomes were compared among the two groups.The CMAFA technique demonstrated an improved rate of R0 resection (89.5% vs. 70.7%, P = .038) and a higher median lymph node yield (24 vs.20, P = .034). The CMAFA-PD group was associated with reduced blood loss (450 vs. 600 ml, P = .049), lower rate of blood transfusion (23.7% vs. 46.3%, P = .035), and shorter length of hospital stay (19 vs. 26 days, P < .001). The rates of 90-day mortality, major morbidity, and readmission were comparable among the two groups.This study demonstrates that CMAFA is a feasible and efficient technique with acceptable perioperative and oncological outcomes in treating patients with PHC.

Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity. The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM. In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM. Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied. A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM. Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM. Glycan variation at a single site was greatest at the Asn-262 glycosite. Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite. Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type. These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.

Interleukin-22 (IL-22) is a potential therapeutic agent for diseases driven by epithelial injury. To characterize the IL-22 expressed by rhesus macaques, animals that are irreplaceable for human disease research, rhesus macaque IL-22 (rhIL-22) was cloned and expressed, and its biological activity and in vivo distribution were examined. It was found that the rhIL-22 gene consists of five introns and six exons, including a short non-coding exon starting 22 bp downstream of a putative TATA box. The amino acid sequence of rhIL-22 showed 95·5% identity to that of humans, and it shared two conserved disulphide bonds, three N-glycosylation sites and all the critical residues for binding to IL-22R1. High levels of IL-22 mRNA were observed in the liver, pancreas, lymphoid tissues and especially in the outer-body barriers such as the intestinal tract of rhesus macaques. Functionally, purified rhIL-22 has a similar but a little earlier effect on signal transducer and activator of transcription 3 phosphorylation at Tyr705 compared with that of commercial human IL-22. The expression of the antibacterial proteins β-defensin-2, S100A8, S100A9, RegIIIα and Muc1 by HT-29 cells was largely upregulated after stimulation with rhIL-22. Recombinant rhIL-22 could also significantly promote the proliferation of human intestinal epithelial cells without affecting cell apoptosis. These data indicate that rhesus macaque IL-22 is highly similar to that of humans in both structure and function, and tests of therapeutic effects of human IL-22 on human diseases in rhesus macaques are warranted., (© 2018 John Wiley & Sons Ltd.)

C2C12 murine myoblasts are a common model for studying muscle differentiation. Platelet endothelial aggregation receptor-1 (PEAR1), an epidermal growth factor repeat-containing transmembrane receptor, is known to participate in platelet contact-induced activation. In the present study, we demonstrated that PEAR1 is involved in the differentiation of C2C12 murine myoblasts. Western blotting and immunofluorescence staining were used to determine PEAR1 expression and localization during C2C12 cell differentiation. Subsequently, PEAR1 expression was activated and inhibited using clustered regularly interspaced short palindromic repeats-dCas9 technology to explore its effects on this process. PEAR1 expression was found to increase over the course of C2C12 cell differentiation. This protein was predominately localized on the membrane of these cells, where it clustered upon induction of differentiation. Expression of the myogenic markers Desmin, MYOG, and MYH2 revealed that PEAR1 positively regulated C2C12 cell differentiation. Moreover, induction of muscle injury by administration of bupivacaine to mice indicated that PEAR1 might play a role in muscle regeneration. In summary, our study confirmed the involvement of PEAR1 in C2C12 cell differentiation, contributing to our understanding of the molecular mechanisms underlying muscle development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Cholangiocarcinoma (CCA) is the second most common primary malignant hepatobiliary cancer worldwide. The circular RNA (circRNA) Cdr1as has been found to play critical roles in various cancers. However, the relationship between circRNA Cdr1as and CCA is still ambiguous. The aim of this study was to explore the expression level of Cdr1as in CCA and to further investigate the clinicopathological and prognostic value of Cdr1as., Patients and Methods: We investigated the circRNA Cdr1as expression in 54 paired tumor and adjacent normal tissues of CCA patients by using quantitative Real-time PCR, and evaluated the relevance between Cdr1as expression level and the clinicopathological features. We further assessed the association of Cdr1as expression with overall survival and its prognostic efficacy., Results: The expression of circRNA Cdr1as in tumor tissues was higher than that in adjacent normal tissues. The overexpression of Cdr1as was closely associated with the advanced TNM stage, lymph node invasion, and postoperative recurrence. The overall survival of CCA patients with high Cdr1as expression was worse than that of the CCA patients with low Cdr1as expression. According to multivariate analysis, the Cdr1as expression could be considered as an independent prognostic biomarker for cholangiocarcinoma with acceptable sensitivity and specificity., Conclusions: Our finding suggested that circRNA Cdr1as may serve as a potential vicious molecular biomarker to predict the aggressive tumor progression and worse prognosis for CCA patients.

Background/aims: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood., Methods: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene., Results: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/β-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/β-catenin signaling pathway as detected by an increased level of β-catenin and phosphorylation of GSK-3β, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells., Conclusion: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objective: To investigate the effect of active immunization on prevention of post-transplantation de novo hepatitis B virus (HBV) infection in patients receiving liver grafts from hepatitis B core antibody (HBcAb) positive donors., Methods: A retrospective analysis was conducted. Eighty-seven children undergoing liver transplantation from HBcAb positive donors admitted to Tianjin First Center Hospital from October 2012 to December 2016 were enrolled, and the data of donors and recipients were collected. The hepatitis B vaccine was given before operation for hepatitis B surface antibody (HBsAb) > 1 000 U/L; hepatitis B immunoglobulin (HBIG) 100 U/kg was given during the operation, in order to prevent children from HBV infected by obtaining passive immunity quickly, children with HBsAb < 200 U/L after operation were injected with hepatitis B vaccine for booster immunization. HBV markers and liver function of recipients were determined before liver transplantation and during the follow-up, which up to April 2017. According to the children got de novo HBV infection after operation or not, the preventive effect of active immunization before and after transplantation operation on HBV infection was analyzed and compared., Results: In 87 children who received HBcAb positive donor livers, 9 (10.3%) developed de novo HBV infection, which occurred in 16 (10, 25) months after liver transplantation. Among the 9 children with HBV infection, 7 children had HBsAb < 1 000 U/L before the operation, the ratio was statistically increased as compared with the children without HBV infection [77.8% (7/9) vs. 37.2% (29/78), P < 0.05]. After the transplantation, 62 children of 78 without HBV infection showed a good response to hepatitis B vaccination, 1 child after inoculation of hepatitis B vaccine, the titer of HBsAb was still less than 200 U/L, 15 children without administration of hepatitis B vaccine, only with HBIG injection for prevention. The HBsAb of children with de nove HBV infection were less than 200 U/L after operation, the ratio was significantly increased as compared with children without HBV infection [100.0% (9/9) vs. 20.5% (16/78), P < 0.01]., Conclusions: The establishment of active immunization method can effectively prevent children with de novo HBV infection occurred in pediatric recipients from HBcAb positive donors with preventive treatment.

Purpose: To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury., Methods: Sixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1β, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation., Results: (1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1β and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups., Conclusion: Level of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR., (Copyright © 2017. Production and hosting by Elsevier B.V.)

Traumatic spinal cord injury (SCI) causes a cascade of degenerative events including cell death, axonal damage, and the upregulation of inhibitory molecules which prevent regeneration and limit recovery. Repulsive guidance molecule A (RGMa) is a potent neurite growth inhibitor in the central nervous system, exerting its repulsive activity by binding the Neogenin receptor. Here, we show for the first time that inhibitory RGMa is markedly upregulated in multiple cell types after clinically relevant impact-compression SCI in rats, and importantly, also in the injured human spinal cord. To neutralize inhibitory RGMa, clinically relevant human monoclonal antibodies were systemically administered after acute SCI, and were detected in serum, cerebrospinal fluid, and in the injured tissue. Rats treated with RGMa blocking antibodies showed significantly improved recovery of motor function and gait. Furthermore, RGMa blocking antibodies promoted neuronal survival, and enhanced the plasticity of descending serotonergic pathways and corticospinal tract axonal regeneration. RGMa antibody also attenuated neuropathic pain responses, which was associated with fewer activated microglia and reduced CGRP expression in the dorsal horn caudal to the lesion. These results show the therapeutic potential of the first human RGMa antibody for SCI and uncovers a new role for the RGMa/Neogenin pathway on neuropathic pain.

Objective: This study aims to explore the clinical efficacy of CpG-based therapy for treating hepatocellular carcinoma (HCC) by skewing polarization toward M1 macrophage from M2., Methods: Pulmonary metastasis rate, overall survival time, and remission rate of 10 patients with HCC treated with transcatheter arterial chemoembolization (TACE) combined with CpG therapy and 10 age-, gender-, and TNM 0 -matched patients treated with TACE (control group) were compared., Results: No pulmonary metastasis rate was 70% in the combined treatment group and 40% in the control group, respectively; and the differences between the two groups were statistically significant (p < 0.05). Median overall survival time was 22 months in the combined treatment group, compared with 6.65 months in the control group (p < 0.05). Remission rate in the combined treatment group (70%) was higher than in the control group (30%), but the differences between these two groups were not statistically significant (p > 0.05)., Conclusion: Compared with TACE, CpG combined with TACE can decrease the pulmonary metastasis rate. This combined therapy can also improve the overall survival time of patients.

Groundwater contamination risk assessment is an important basis for the protection of groundwater resources and the prevention and control of groundwater pollution. Its evaluation system is usually composed of three elements, which is vulnerability, pollutant source load and groundwater value. The pollutant source load plays an important role in risk assessment. Because of the difference among methods for pollutant sources load quantification, there will inevitably be different demand for the basic information survey on pollutant sources, as well as unknown impact on the final assessment results. In order to explore the impact of quantitative methods for pollutant sources load on groundwater contamination risk assessment, a case study was conducted in the mesoscale region of alluvial fan in Hutuo River, China. The two representative methods of grading index and quantitative index assessment systems were applied to quantify the pollutant sources load, in combination with the same vulnerability and groundwater value. The results constructed from different risk assessment systems were compared. The results showed that there were great differences between the two methods of quantification for pollutant sources load, and the result of contamination risk assessment also revealed significant differences in the feature of risk valve and the spatial distribution of the risk levels. The results of contamination risk assessment were strongly influenced by the choice of quantification for pollutant sources load methods. The grading index method was suitable for large scale region with lower precision of basic information and was simple, and the results of assessment had relatively lower reliability. The quantitative index method was suitable for the mesoscale and micro-scale region with higher precision of basic information and was relatively complicated, and the results of assessment had relatively higher reliability. It was shown that the scale effect of evaluation region had an important influence on the choice of methods.

Background: The association between the tumor necrosis factor-alpha gene (TNF-a) -238G/A polymorphism and the breast cancer has been analyzed in several studies, but the results have been inconclusive. We then performed a meta-analysis to get a precise estimation of the association., Methods: Eight case-control studies with a total of 37,257 cases and 39,564 controls were identified by searching the ISI Web of Knowledge database and the PubMed database up to August 2014., Results: Overall, no association was found between TNF-alpha-238G/A polymorphism and breast cancer in any of genetic model (additive model OR = 1.06, 95%CI: 0.94-1.21, Pheterogeneity = .02; homozygous model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98; dominant model OR = 1.06, 95%CI: 0.92-1.21, Pheterogeneity = .01; recessive model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98). Furthermore, no significant association was identified when stratified by ethnicity (Caucasian, Asian)., Conclusion: This meta-analysis indicated that the TNF-alpha-238G/A polymorphism is not associated with breast cancer risk in the overall population.

Objective: To investigate the effect of stimulation of Human Bronchial Epithelial Cells (HBEC) by Der p1 and PM2.5 on the expression of innate immune cell factors to find new therapeutic targets for treatment of bronchial asthma., Materials and Methods: The Der p1 antigen exposure model in the HEBC line, 16HBE-14o, was established in vitro. PM2.5 at a concentration of 50 µM/cm2, was added to these cells for 0.5 h, 1 h, 2 h and 3 h. Cells were treated with the following reagents for the indicated times: 300 ng/mL Der p1 for 21 h, 50 µM/cm2 PM2.5 for 3 h, 10 mM Nac for 3 h and PM2.5 contamination for 3 h. The experiment was divided into five groups: control (group A), Der p1 exposure group (group B), PM2.5 treated group (group C), PM2.5+Der p1 exposure group (group D), Nac+PM2.5+Der p1 exposure group (group E). ELISA method was adopted to test the expression levels of malondialdehyde, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP), and Real-time RT-PCT was used to measure IL-25, IL-33 and TSLP mRNA., Results: The protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group D were significantly higher than those in the other groups, while the protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group E were significantly lower than those in group D (p<0.05)., Conclusions: PM2.5 can enhance the Der p1 antigen-induced HBEC innate immune response through the expression of IL-25, IL-33 and TSLP, which may exacerbate the occurrence rate of bronchial asthma.

This study investigated the occurrence, seasonal-spatial distribution characteristics, and attenuation process of 15 pharmaceuticals and personal care products (PPCPs) in riverside sections of Beiyun River of Beijing. The overall PPCP levels both in surface water and riverside groundwater were moderate on the global scale, and showed higher concentrations in the dry season mainly caused by water temperature variation. Caffeine (CF), carbamazepine (CBZ), metoprolol (MTP), N,N-diethyl-meta-toluamide (DEET), diclofenac (DF), bezafibrate (BF), and gemfibrozil (GF) were seven representative PPCPs, because the rest eight studied compounds occurred in low concentrations and less than 15% of the total concentration of PPCPs. Caffeine and bezafibrate, respectively, was the most abundant compound in surface water and riverside groundwater, with median concentrations of 3020.0 and 125.0 ng L -1 . Total concentrations of PPCPs in surface water were much higher than those in the riverside groundwater spatially. Attenuation of PPCPs during riverbank filtration was largely depending on the sources, site hydrogeological conditions, and physical-chemical properties of PPCPs, also was influenced by dissolved organic matter and environmental physicochemical parameters. CF, MTP, DEET, and CBZ were potential groundwater attenuation contaminants; DF, BF, and GF were groundwater-enriched contaminants based on their removal rates. Predominant removal mechanism of PPCPs like CF was biodegradation. Attenuation simulation showed that the one-way supply between Beiyun River and riverside groundwater, and further confirmed Beiyun River, was the main source of pharmaceutical compounds in the riverside groundwater.

Aim: To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma., Methods: In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumor-adjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively., Results: CXCR7 expression was up-regulated in gastric cancer tissues ( P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node ( r = 0.338, P = 0.000) and liver metastasis ( r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues ( χ 2 = 6.669, P = 0.010; χ 2 = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer ( r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12., Conclusion: The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer., Competing Interests: Conflict-of-interest statement: The authors declare no competing financial interests and have no conflicts of interest to disclose.

Objective: To investigate the expression of long noncoding RNA CCAT1 in cholangiocarcinoma (CCA) and to assess the CCAT1 expression as a prognostic biomarker for CCA., Patients and Methods: The CCAT1 expression in tumor tissues and paired adjacent normal tissues from 91 CCA patients was detected by quantitative real-time PCR. The association of the CCAT1 expression with clinicopathological features of CCA patients and the prognostic value of the CCAT1 expression for overall survival was also evaluated by Kaplan-Meier, Cox regression model and ROC analysis., Results: The CCAT1 expression was significantly upregulated in CCA tumor tissues compared with adjacent normal tissues. The CCAT1 expression was obviously associated with histological differentiation, lymph node invasion, and TNM stage. The overall survival of CCA patients with high CCAT1 expression was worse. Furthermore, the CCAT1 expression could be considered as an independent prognostic factor in predicting the overall survival for CCA patients., Conclusions: Our study showed that lncRNA CCAT1, which was upregulated and associated with aggressive malignant behavior, may serve as a novel prognostic biomarker and potential therapeutic target for cholangiocarcinoma.

Polymeric immunoglobulin receptors(pIgR) are key participants in the formation and secretion of secretory IgA(S-IgA), which is critical for the prevention of microbial infection and colonization in the respiratory system. Although increased respiratory colonization and infections are common in HIV/AIDS, little is known about the expression of pIgR in the airway mucosa of these patients. To address this, the expression levels of pIgR in the tracheal mucosa and lungs of SHIV/SIV-infected rhesus macaques were examined by real-time RTPCR and confocal microscopy. We found that the levels of both PIGR mRNA and pIgR immunoreactivity were lower in the tracheal mucosa of SHIV/SIV-infected rhesus macaques than that in non-infected rhesus macaques, and the difference in pIgR immunoreactivity was statistically significant. IL-17A, which enhances pIgR expression, was also changed in the same direction as that of pIgR. In contrast to changes in the tracheal mucosa, pIgR and IL-17A levels were higher in the lungs of infected rhesus macaques. These results indicated abnormal pIgR expression in SHIV/SIV, and by extension HIV infections, which might partially result from IL-17A alterations and might contribute to the increased microbial colonization and infection related to pulmonary complications in HIV/AIDS.

Objective: To investigate the clinical application of combined multiple artery-first approach to pancreatoduodenectomy. Methods: The clinical data of 53 patients who were diagnosed with peripancreatic head tumor at Department of Biliary-Pancreatic Surgery of Second Affiliated Hospital of Harbin Medical University between June 2013 and June 2015 was retrospectively analyzed.Pancreatic enhanced CT scan, magnetic resonance cholangiopancreatography, ultrasonography and tumor marker detection were applied for all the patients preoperatively.The 53 patients were operated by combined multiple artery-first approach(superior+ posterior approach, superior+ inferior approach, posterior+ inferior approach, superior+ posterior+ inferior approach) according to individualized therapeutic concept.And 42 patients underwent pancreatoduodenectomy, 9 patients underwent palliative operation and 2 patients just received exploratory operation. Results: Forty-two peripancreatic head tumor patients underwent pancreatoduodenectomy by applying combined multiple artery-first approach.The median operation time and intraoperative blood loss were (5.4±3.1)hours and (366±297)ml and the harvested lymph node and duration of hospital stay were 19±5 and (14.0±5.6)days.Nine patients underwent "total mesopancreas excision" and the rate of postoperative pancreatic fistula and R0 resection were 38.1% and 88.1%. Anomalous origin hepatic right artery was detected in one patients during the operation and no death occurred within 30 days postoperatively. Conclusion: According to the tumor location and patient's condition, individualistically applying combined multiple artery-first approach can reduce intraoperative blood loss, terminate unnecessary surgery, detect anomalous origin artery, make the tumor resection more radical and pancreatoduodenectomy more safety.

Due to the large surgical trauma and postoperative complications, the perioperative management of pancreaticoduodenectomy has been one of the urgent problems to be solved by the surgeons. With the development of modern medicine, enhanced recovery after surgery (ERAS) comes into being, basing on anti-stress mechanism and multi-disciplinary team, and the perioperative management of pancreaticoduodenectomy has been optimized and improved continuously. The surgeons through a range of measures that had evidence-based medicine basis to mitigate the extent of surgical trauma stress, reduce the incidence of postoperative complications, shorten patient recovery time previously healthy state, and achieve maximize benefit for patients. Currently, the ERAS application in the specific aspects of pancreaticoduodenectomy remains contentious. However, with the emergence of evidence-based medicine, ERAS is constantly being refined. Therefore, this article combined with ERAS guidelines and expert consensus is of great significance to deepen the research and understanding of ERAS in pancreaticoduodenectomy.

MicroRNAs (miRNAs) play critical roles in the proliferation of bovine preadipocytes. miR-2400 is a novel and unique miRNA from bovines. In the present study, we separated and identified preadipocytes from bovine samples. miR-2400 overexpression increased the rate of preadipocyte proliferation, which was analyzed with a combination of EdU and flow cytometry. Simultaneously, functional genes related to proliferation (PCNA, CCND2, CCNB1) were also increased, which was detected by real-time PCR. Furthermore, luciferase reporter assays showed that miR-2400 bound directly to the 3'untranslated regions (3'UTRs) of PRDM11 mRNA. These data suggested that miR-2400 could promote preadipocyte proliferation by targeting PRDM11., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Competing endogenous RNAs (ceRNAs) represent a novel layer regulations of long non-coding RNAs (lncRNAs) and genes that play important roles in cancer pathogenesis by binding microRNAs (miRNAs). However, the competition mechanism of ceRNAs in cholangiocarcinoma (CHOL) is not fully understood. In this study, we constructed a dysregulated ceRNA competitive network (CCEN) to globally characterize the competing difference between CHOL and normal tissues. Then, we integrated affinity propagation and Kaplan‑Meier (K-M) methods to identify functional clusters associated with survival. A total of 7 key ceRNA clusters were identified. Further functional annotation analyses found that Cluster23 and Cluster32 involved cell based functions, and the loss of ceRNA competitive relations in clusters may contribute to CHOL, by disturbing important biological processes, such as 'Pathway in cancer', MAPK and Neurotrophin signaling pathway. This study provides further insights into understanding the competitive mechanism of ceRNAs in CHOL.

Purpose: We aimed to characterize the clinical profile, etiology, and outcomes of young Chinese patients with Budd-Chiari syndrome treated with recanalization., Methods: A total of 35 consecutive young patients (≤25 years of age) with primary Budd-Chiari syndrome treated with recanalization at our center were enrolled in this study between March 2011 and December 2014. Data on baseline information, etiology tests, therapeutic recanalization strategies, and follow-up were collected., Results: The most common clinical feature was ascites, present in 33 cases (94%). Hepatic vein obstruction was present in 60% (21/35) of patients, inferior vena cava obstruction in 3% (1/35), and combined obstruction in 37% (13/35). The most common risk factor for thrombosis was hyperhomocysteinemia (14/35, 40%). Recanalization was technically successful in 32 of 35 patients (91%), and clinically successful in 28 of these 32 patients (88%). The cumulative 1- and 3-year primary patency rates were 75.2 and 54.3%, respectively. The cumulative 1- and 3-year secondary patency rates were 89.3 and 89.3%, respectively. The cumulative 1- and 3-year survival rates were 96.9 and 93.8%, respectively., Conclusion: In this study, the most common type of lesion was hepatic vein obstruction, the most common thrombotic risk factor was hyperhomocysteinemia, and recanalization resulted in good mid-term outcomes in young Chinese patients with Budd-Chiari syndrome.

Objective: To determine the long-term patency and survival of percutaneous recanalization for hepatic vein (HV)-type Budd-Chiari syndrome (BCS)., Methods: From March 2009 to November 2014, consecutive symptomatic HV-type BCS patients were treated by percutaneous recanalization in our centers. These patients underwent main HV (MHV) or accessory HV (AHV) recanalization. Data on patient characteristics, technical success, clinical success, long-term patency, and survival were collected and analyzed., Results: During the enrolled periods, a total of 143 symptomatic HV-type BCS patients were treated by percutaneous recanalization in our centers. Technical success was achieved in 140 of 143 patients. One hundred eleven patients underwent MHV recanalization, and 29 underwent AHV recanalization. Clinical success was achieved in 136 of 140 patients. The mean MHV/AHV pressure decreased from 33.5 ± 4.1 mmHg before treatment to 12.5 ± 3.1 mmHg after treatment (p = 0.000). The 136 patients were followed for 7-75 months (mean 33.9 ± 15.3 months). Twenty-eight patients experienced re-obstruction of MHV (n = 24) or AHV (n = 4) at 3 to 36 months (mean 18.0 ± 11.5 months) after treatment. The cumulative 1-, 3-, and 6-year primary patency rates were 91.1, 77.4, and 74.0%, respectively. The cumulative 1-, 3-, and 6-year secondary patency rates were 97.0, 92.4, and 88.8%, respectively. The cumulative 1-, 3-, and 6-year survival rates were 97.7, 92.2, and 90.0%, respectively., Conclusion: Percutaneous recanalization can provide good long-term patency and survival in HV-type BCS patients.

Background: The aim of this paper was to evaluate the effectiveness and long-term outcome of combined catheter-directed thrombolysis (CDT) and iliac vein recanalization in management of iliac vein compression syndrome (IVCS) with secondary acute deep vein thrombosis (DVT)., Methods: From January 2006 to February 2014, consecutive patients with IVCS and secondary acute DVT were treated with combined CDT and iliac vein recanalization. Data on technical success, clinical success, and follow-up were analyzed respectively., Results: A total of 55 patients were included in this retrospective study. Technical success was achieved in all patients. The filter was placed in 24 patients and all filters were successfully retrieved after treatment. The total dose of urokinase ranged from 1.6×106 to 6.6×106 units (mean, 3.72±0.13×106 units). The thrombus were totally dissolved in all patients. The iliac venous stents were placed in 7 patients. Clinical success was achieved in all patients. During the follow-up of 6-103 months (mean, 35.87±27.86 months), eight patients experienced the recurrence of DVT 1-39 months (mean, 13.13±12.25 months) after treatment. The cumulative 1-, 3-, and 6-year primary patency rates were 88.5, 85.3 and 80.0%, respectively. The cumulative 1-, 3-, and 6-year secondary patency rates were 98.0, 94.2, and 88.7%, respectively. At univariate and multivariate analysis, the independent predictor of recurrence of DVT was INR<2 after treatment., Conclusion: Combined CDT and iliac vein recanalization could provide a favorable effectiveness and long-term outcome for patients with IVCS and secondary acute DVT.

The aim of the present study was to determine the role of interleukin-6 (IL-6) in the epithelial-mesenchymal transition (EMT) of human intrahepatic biliary epithelial cell (HIBEC) lines in vitro. HIBECs were stimulated with IL-6 at concentrations of 0, 10, 20, 50 and 100 µg/l for 24 h. A wound healing and Transwell assay were performed to determine the migratory and invasive capacity of HIBECs, respectively. Following 24 h of incubation, IL-6 at 10 and 20 µg/l significantly increased the number of migrated and invaded cells (P<0.05), while stimulation with 50 and 100 µg/l IL-6 resulted in a further increase of the migratory and invasive capacity compared to that in all other groups (P<0.05). Furthermore, reverse-transcription quantitative polymerase chain reaction and western blot analyses were used to detect the mRNA and protein expression of EMT markers E-cadherin and vimentin in HIBECs. Decreased mRNA levels of E-cadherin accompanied by higher mRNA levels of vimentin were observed in the 10, 20, 50, 100 µg/l IL-6 groups compared to those in the 0 µg/l group (all P<0.05). Furthermore, the protein expression of E-cadherin was decreased, while that of vimentin was increased in the 50 and 100 µg/l IL-6 groups compared to those in the 0, 10 and 20 µg/l IL-6 groups (all P<0.05). The present study therefore indicated that IL-6 promoted the process of EMT in HIBECs as characterized by increased migration and invasion of HIBECs and the typical changes in mRNA and protein expression of the EMT markers E-cadherin and vimentin.

Our study investigated whether microRNA-122 (miR-122) played important roles in the proliferation, invasion and apoptosis of human cholangiocarcinoma (CC) cells. QBC939 and RBE cells lines were chosen and divided into five groups: miR-122 mimic group, anti-miR-122 group, negative control (NC) group, mock group and blank group. MiR-122 expression was measured by qRT-PCR. Roles of miR-122 in cell proliferation, apoptosis and invasion were investigated using MTT assay, flow cytometer and Transwell invasion assay, respectively. MiR-122 expression was lower in CC tissues and QBC939 cell than that in normal bile duct tissues, HCCC-9810 and RBE cells. In both QBC939 and RBE cells lines, miR-122 expression was higher in miR-122 mimic group than that in NC group, mock group and blank group; opposite results were found in anti-miR-122 group. Cell proliferation and invasion were remarkably inhibited in miR-122 mimic group after 48 h/72 h transfection, while apoptotic cells numbers were much greater in miR-122 mimic group; the opposite results were obtained from anti-miR-122 group (all P < 0.05). MiR-122 expression was significantly weaker in CC tissues, and miR-122 overexpression might play pivotal roles in inhibiting proliferation, stimulating apoptosis and suppressing invasion of CC cells, suggesting a new target for CC diagnosis and treatment.

Purpose: This study aimed at investigating the feasibility and effectiveness of retrograde puncture assisted hepatic vein (HV) recanalization in management of Budd-Chiari syndrome (BCS) patients with segmental obstruction of HV., Materials and Methods: From May 2011 to August 2014, 76 BCS patients with obstruction of HV were treated by routine transjugular HV recanalization in our center. Among them, 17 patients with segmental obstruction (obstruction length >1 cm) of HV experienced failure of the routine transjugular HV recanalization and underwent retrograde puncture assisted HV recanalization. Data on technical success, clinical success and follow-up were collected and analyzed retrospectively., Results: Retrograde puncture assisted HV recanalization was technically successful in 14 of 17 (82 %) patients. Of these 14 patients, 12 patients underwent HV balloon dilation, and 2 patients underwent HV stent insertion. No procedure-related complications occurred in any of our patient. Clinical success was achieved in all of the 14 patients who experienced technical success. The mean HV pressure decreased from 43.6 ± 6.7 cmH2O before treatment to 18.4 ± 4.8 cmH2O after treatment (P < 0.001). BCS-related symptoms began to improve on the next day following the treatment. During 4-43 months (mean 17.4 ± 10.8 months) of follow-up, three patients experienced re-obstruction of HV., Conclusions: Retrograde puncture assisted HV recanalization is a simple, safe, and effective treatment for BCS patients with segmental obstruction of HV. It can serve as an additional treatment option for patients who experience the technical failure of routine transjugular HV recanalization.

Purpose: To evaluate the clinical value of accessory hepatic vein (AHV) intervention in the treatment of Budd-Chiari syndrome (BCS)., Patients and Methods: From August 2008 to July 2014, consecutive patients with BCS caused by obstruction of three hepatic veins (HVs) with or without obstruction of inferior vena cava (IVC) were treated by recanalization or transjugular intrahepatic portosystemic shunt in our center. Patients who had the compensatory AHV and successfully underwent recanalization of AHV outflow were enrolled in this retrospective study. The clinical response to AHV drainage was analyzed., Results: Compensatory AHV was found in 69 of 97 (71.1%) patients, and 66 patients successfully underwent recanalization of AHV outflow (IVC recanalization, n = 49; AHV recanalization, n = 15; both, n = 2). In total, 78 AHVs were used instead of HV as the hepatic drainage vein after treatment. Fifty-five patients had one AHV, 10 patients had two AHVs, and 1 patient had three AHVs. The average diameter of all AHV stems was 8.0 ± 2.6 mm (range 5-21 mm). Clinical response to AHV drainage was positive in all patients. Patients' symptoms and liver function improved progressively after treatment. During the follow-up of 3-74 months (average 39.4 ± 11.0 months), 11 patients experienced reobstruction at 6 to 36 months (average 16.8 ± 9.8 months) after treatment., Conclusion: Compensatory AHV can be effectively used instead of HV for drainage of hepatic blood in patients with BCS. AHV intervention can help to simplify the BCS treatment procedure.

Purpose: To investigate the feasibility, safety, and effectiveness of combined thrombus aspiration and inferior vena cava (IVC) recanalization for Budd-Chiari syndrome (BCS) patients with IVC thrombosis., Materials and Methods: From March 2011 to October 2014, 17 consecutive BCS patients with IVC thrombosis [male 13, female 4 (mean age 52.6 ± 8.4 years, range 43-72 years)] treated by combined thrombus aspiration and IVC recanalization were enrolled in this retrospective study. An 8F guiding catheter was used as the aspiration catheter. During the treatment, the aspiration catheter was placed from the right femoral vein to the IVC thrombi, and a 20-ml syringe was connected with the aspiration catheter for thrombus aspiration. IVC recanalization was performed after thrombus aspiration. Data on technical success, clinical success, and follow-up were analyzed., Results: Technical success was achieved in all patients. After thrombus aspiration, 12 patients had no visible thrombi on IVC venography, while 5 patients were shown to have the IVC mural thrombi. Afterwards, 13 patients were treated by IVC balloon dilation, and 4 patients were treated by IVC stent insertion. No patient experienced dyspnea after treatment. The average IVC pressure decreased from 29.8 ± 3.4 cmH2O to 8.6 ± 2.1 cmH2O (P < 0.001). Clinical success was achieved in all patients. The average follow-up period was 15.3 ± 11.6 months (range 2-44 months). Long-term IVC patency was achieved in 15 of 17 patients., Conclusion: Combined thrombus aspiration and IVC recanalization can be a safe and effective method for BCS patients with IVC thrombosis.

In order to investigate the characteristics of 5 typical kinds of fluoroquinolones (FQs) pollution in waters from a city, surface water and groundwater samples from main drainage rivers and typical areas were collected, respectively. The conventional test and FQs concentrations analysis of the water samples were conducted. The results showed the concentration and composition of FQs in groundwater differed substantially from those in surface water. The average concentration of FQs in surface water was 789.1 ng x L(-1) with the main components of ofloxacin (OFL) and lomefloxacin (LOM). This value was higher than the average concentration of FQs in groundwater: 342.7 ng x L(-1) with the main components of norfloxacin (NOR) and lomefloxacin (LOM). The enrofloxacin (ENR) exhibited relatively lower levels in both surface water and groundwater as compared to others. The highest FQs concentrations in surface water were found in trenches, followed by tributaries and the main stream. For groundwater, FQs concentrations were relatively higher in the sewage riverside. A decreasing trend of FQs concentration was monitored with the increasing distance of sampling points to the drainage rivers and all components mentioned above showed similar changing trends. The results of this study preliminarily indicated that FQs in groundwater along the riverside probably came from the surface water.

Purpose: To investigate the feasibility, strategy, and long-term outcome of percutaneous recanalization for combined-type Budd-Chiari syndrome (BCS)., Methods: From December 2007 to August 2014, consecutive symptomatic combined-type BCS patients were treated by percutaneous recanalization in our centers. Inferior vena cava (IVC) recanalization was the first-stage treatment for all patients. Recanalization of one hepatic vein (HV) was the second-stage treatment for the selected patients. If the patient had the compensatory and patent accessory HV (AHV), we observed this patient for 7 days after IVC recanalization. If the symptoms of portal hypertension improved, HV recanalization was not needed. Otherwise, HV recanalization was performed. If the patient had no patent AHV, HV recanalization was performed 3 days after IVC recanalization. Data on technical success, clinical success, and follow-up were analyzed, respectively., Results: Sixty-two symptomatic combined-type BCS patients were enrolled. Technical success of percutaneous recanalization was achieved in 60 patients. Among them, 52 patients had the patent AHV and underwent single IVC recanalization, and 8 patients had no patent AHV and underwent combined IVC and HV recanalization. Clinical success was achieved in all of the 60 patients. Three patients died during the follow-up. The cumulative 1-, 2-, and 4-year survival rates were 98.3%, 96.5%, and 92.7%, respectively., Conclusion: Percutaneous recanalization is suitable for most combined-type BCS patients. Treatment strategy can be made according to the situation of AHV. If the patient has the patent AHV, single IVC recanalization is enough. Otherwise, combined IVC and HV recanalization should be performed.

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Claudins are aberrantly expressed in aggressive breast cancer. However, the relationship between claudins and VM formation is not clear. We examined VM in two human breast cancer cell lines with different aggressive capabilities (MDA-MB-231 and MCF-7 cells) and one human umbilical vein endothelial cell line (HUVEC). Both HUVEC and MDA-MB-231 cells formed vascular channels in Matrigel cultures, while MCF-7 cells did not. Western blot analysis revealed a possible correlation between claudin-4 and -6 expression in breast cancer cell lines and tumor aggressiveness, with protein levels correlating with the ability to form vascular channels. Treatment of MDA-MB-231 and HUVEC cells with claudin-4 monoclonal antibodies completely inhibited the ability of cells to form vascular channels. Moreover, knockdown of claudin-4 by short hairpin RNA completely inhibited tubule formation in MDA-MB-231 cells. Overexpression of claudin-4 in MCF-7 cells induced formation of vascular channels. Immunocytochemistry revealed that membranous claudin-4 protein was significantly associated with vascular channel formation. Collectively, these results indicate that claudin-4 may play a critical role in VM in human breast cancer cells, opening new opportunities to improve aggressive breast cancer therapy.

Aim: To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography (CT) perfusion of rabbit VX2 tumor., Methods: Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential (120 kVp) protocol with 350 mgI/mL contrast medium and filtered back projection, and a low tube potential (80 kVp) protocol with 270 mgI/mL contrast medium with iterative reconstruction. Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor. Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated., Results: A 38% reduction in contrast medium dose (360.1 ± 13.3 mgI/kg vs 583.5 ± 21.5 mgI/kg, P < 0.001) and a 73% decrease in radiation dose (1898.5 mGy • cm vs 6951.8 mGy • cm) were observed. Interestingly, there was a strong positive correlation in hepatic arterial perfusion (r = 0.907, P < 0.001; r = 0.879, P < 0.001), hepatic portal perfusion (r = 0.819, P = 0.002; r = 0.831, P = 0.002), and hepatic blood flow (r = 0.945, P < 0.001; r = 0.930, P < 0.001) as well as a moderate correlation in hepatic perfusion index (r = 0.736, P = 0.01; r = 0.636, P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor. These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumor-to-liver CNR during arterial and portal venous phases (5.63 ± 2.38 vs 6.16 ± 2.60, P = 0.814; 4.60 ± 1.27 vs 5.11 ± 1.74, P = 0.587)., Conclusion: Compared with the conventional protocol, low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.

The present study was designed to examine the effect of neovibsanin B on glioma cell viability, apoptosis and on the survival time in mice bearing tumor xenografts. The results demonstrated that neovibsanin B significantly reduced the cell viability of GL261-NS and GL261-AC cells in a dose-dependent manner. However the inhibition of proliferation was more significant in GL261-NS cells. The IC50 value of neovibsanin B against GL261-NS and GL261-AC cells is 5 and 25 nM, respectively. The inhibitory effect of neovibsanin B on cell growth was more effective than that of vincristine (VCR) (P < 0.05). We also observed a significant decrease in sphere-forming ability of GL261-NS cells on treatment with neovibsanin B. The number of colonies formed by GL261-NS cells on treatment with neovibsanin B, VCR and DMSO were 3.34 ± 1.02, 12.53 ± 3.46 and 61.34 ± 9.89% respectively after 7 days. The flow cytometry revealed a marked increase in apoptotic cell death of GL261-NS cells on treatment with neovibsanin B. The western blots showed a significant decrease in the level of activated caspase-3 on treatment with neovibsanin B after 24 h. In addition, neovibsanin B increased the median survival time of glioma-bearing mice (P < 0.05). Therefore, neovibsanin B effectively inhibits glioma cell viability by inducing apoptosis, and can be a potent therapeutic agent for the treatment of malignant glioma.

Objective: To evaluate the clinical value of Solitaire AB stents in the embolization of intracranial aneurysms., Patients and Methods: Solitaire AB stents were applied in treating 69 aneurysms in 65 patients. Among them, there were 67 "wide neck" aneurysms and two "narrow neck" aneurysms. Of the 69 aneurysms, there were 40 aneurysms in the posterior communicating artery, 13 in the ophthalmic artery segment, one in the cavernous segment of the internal carotid artery, three in the middle cerebral artery, one in the anterior communicating artery, eight in the vertebral artery, and three in the basilar artery. The treatment techniques used included transposition, parallel technique, post-release technique, and salvage stenting., Results: Immediate angiographic results showed complete thrombosis in 63 cases, residual aneurysm neck in two cases and partial embolism in four cases. Intraoperative aneurysm rupture was found in two cases, of which bleeding was stopped with continued filling. Postoperative hydrocephalus cerebrospinal fluid shunt was performed in one case. Coil shift was observed in two cases. No further bleeding cases occurred during the clinical follow-up. Of 14 patients who had undergone angiographic follow-up, three cases had recurrence and one case received re-embolization., Conclusions: Solitaire AB stent is clinically feasible when applied for the embolization of intracranial aneurysms using multiple techniques and, thus, warrants clinical promotion.