Central hepatectomy is amongst the most difficult surgeries of liver tumors. For the routine local excision of a tumor, if the tumor has invaded the blood vessels or bile duct of the liver, then half of the liver or three lobes of the liver are resected. This results in two major drawbacks, one of which is that the residual hepatic lobe may not compensate for the damage, so it is not possible to perform conventional partial resection. The other is that the volume of normal liver tissue removed may be much more than the volume of tumor removed, causing substantial waste. In the present study, surgery was performed to resect a central liver tumor. In that surgery, the V segment and parts of the IV, VI and VIII segments were resected, and the blood supply and biliary drainage of the left hepatic lobe were kept intact. However, for the remaining VI, VII and VIII segments of the right hepatic lobe, only the blood supply from the portal vein was maintained and no arterial blood supply or biliary drainage was kept so that the patient had the opportunity to undergo radical resection and successful rehabilitation. The reason these opportunities may be possible is that the residual right liver is a temporary replacement therapy in the perioperative period. Therefore, for central hepatic tumors, particularly tumors that have invaded the neighboring bile ducts or blood vessels, if the blood supply and biliary drainage on one side is maintained and the blood supply to the other side from the portal vein is kept intact, then it is possible to perform radical resection. This provides a novel approach to the clinical resection of central liver tumors.
middle lobe liver tumor; middle hepatectomy; biliary drainage; blood supply
Genetic susceptibility to alcoholic cirrhosis (AC) exists. We previously demonstrated hepatic mitochondrial DNA (mtDNA) damage in patients with AC compared with chronic alcoholics without cirrhosis. Mitochondrial transcription factor A (mtTFA) is central to mtDNA expression regulation and repair; however, it is unclear whether there are specific mtTFA single nucleotide polymorphisms (SNPs) in patients with AC and whether they affect mtDNA repair. In the present study, we screened mtTFA SNPs in patients with AC and analyzed their impact on the copy number of mtDNA in AC. A total of 50 patients with AC, 50 alcoholics without AC and 50 normal subjects were enrolled in the study. SNPs of full-length mtTFA were analyzed using the polymerase chain reaction (PCR) combined with gene sequencing. The hepatic mtTFA mRNA and mtDNA copy numbers were measured using quantitative PCR (qPCR), and mtTFA protein was measured using western blot analysis. A total of 18 mtTFA SNPs specific to patients with AC with frequencies >10% were identified. Two were located in the coding region and 16 were identified in non-coding regions. Conversely, there were five SNPs that were only present in patients with AC and normal subjects and had a frequency >10%. In the AC group, the hepatic mtTFA mRNA and protein levels were significantly lower than those in the other two groups. Moreover, the hepatic mtDNA copy number was significantly lower in the AC group than in the controls and alcoholics without AC. Based on these data, we conclude that AC-specific mtTFA SNPs may be responsible for the observed reductions in mtTFA mRNA, protein levels and mtDNA copy number and they may also increase the susceptibility to AC.
alcoholic cirrhosis; mitochondrial transcription factor A; single nucleotide polymorphisms; mitochondrial DNA; susceptibility
A novel design and facile synthesis process for carbon based hybrid materials, i.e., cobalt monoxide (CoO)-doped graphitic porous carbon microspheres (Co-GPCMs), have been developed. With the synthesis strategy, the mixture of cobalt gluconate, α-cyclodextrin and poly (ethylene oxide)106-poly (propylene oxide)70-poly (ethylene oxide)106 is treated hydrothermally, followed by pyrolysis in argon. The resultant Co-GPCMs exhibits a porous carbon matrix with localized graphitic structure while CoO nanodots are embedded in the carbon frame. Thus, the Co-GPCMs effectively combine the electric double-layer capacitance and pseudo-capacitance when used as the electrode in supercapacitor, which lead to a higher operation voltage (1.6 V) and give rise to a significantly higher energy density. This study provides a new research strategy for electrode materials in high energy density supercapacitors.
AIM: To study the effects of Helicobacter pylori (H. pylori) tumor necrosis factor-α (TNF) inducing protein (Tip-α) on cytokine expression and its mechanism.
METHODS: We cloned Tip-α from the H. pylori strain 26695, transformed Escherichia coli with an expression plasmid, and then confirmed the expression product by Western blotting. Using different concentrations of Tip-α that affected SGC7901 and GES-1 cells at different times, we assessed cytokine levels using enzyme-linked immunosorbent assay. We blocked SGC7901 cells with pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of nuclear factor κB (NF-κB). We then detected interleukin (IL)-1β and TNF-α levels in SGC7901 cells.
RESULTS: Western blot analysis using an anti-Tip-α antibody revealed a 23-kDa protein, which indicated that recombinant Tip-α protein was recombined successfully. The levels of IL-1β, IL-8 and TNF-α were significantly higher following Tip-α interference, whether GES-1 cells or SGC-7901 cells were used (P < 0.05). However, the levels of cytokines (including IL-1β, IL-8 and TNF-α) secreted by SGC-7901 cells were greater than those secreted by GES-1 cells following treatment with Tip-α at the same concentration and for the same duration (P < 0.05). After blocking NF-κB with PDTC, the cells (GES-1 cells and SGC-7901 cells) underwent interference with Tip-α. We found that IL-1β and TNF-α levels were significantly decreased compared to cells that only underwent Tip-α interference (P < 0.05).
CONCLUSION: Tip-α plays an important role in cytokine expression through NF-κB.
Helicobacter pylori; Tumor necrosis factor-α inducing protein; Interleukin-1β; Interleukin-8; Tumor necrosis factor-α; Nuclear factor-κB
The present study describes the diagnosis and treatment of hyperfibrinolysis following surgery in a 25-year-old female patient. An examination revealed that the left kidney had been affected by severe hydronephrosis for two weeks prior to hospitalization. The diagnosis of a parapelvic cyst was obtained by preoperative intravenous pyelogram (IVP), computed tomography (CT) and upper left urinary tract retrograde pyelography. Unroofing of the left parapelvic cyst was performed by open surgery. The patient exhibited symptoms of shock 48 h later, and her hemoglobin (Hb) levels dropped to only 62.2 g/l. To treat this, 400 ml erythrocyte suspension transfusion was administered 3 times every other day. The patient’s Hb levels remained between 50 and 60 g/l. The D-dimer assay index rose from 0.3 to 16 mg/l and the fibrin degradation product (FDP) levels progressively increased following the hemorrhage, while the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (Fg) index were all within normal levels. p-Aminomethylbenzoic acid (PAMBA; 0.5 g) was administered to the patient every day, and as a consequence the Hb levels rose steadily from the next day onwards. After a one week course of PAMBA treatment, the patient’s condition became stable. Blood coagulation and fibrinolytic function measurements were all within the normal ranges in the three months following the surgery. Delayed hemorrhage following surgery should be considered as a possible cause of hyperfibrinolysis. Monitoring FDP and D-dimer levels may aid a rapid and clear diagnosis. Anti-fibrinolytic therapy, such as PAMBA treatment, is safe and effective for use against the type of hemorrhage caused by hyperfibrinolysis.
parapelvic cyst; hyperfibrinolysis; diagnosis and treatment
Intestinal ischemia-reperfusion (I/R) plays an important role in critical illnesses. Gut flora participate in the pathogenesis of the injury. This study is aimed at unraveling colonic microbiota alteration pattern and identifying specific bacterial species that differ significantly as well as observing colonic epithelium change in the same injury model during the reperfusion time course.
Denaturing gradient gel electrophoresis (DGGE) was used to monitor the colonic microbiota of control rats and experimental rats that underwent 0.5 hour ischemia and 1, 3, 6, 12, 24, and 72 hours following reperfusion respectively. The microbiota similarity, bacterial diversity and species that characterized the dysbiosis were estimated based on the DGGE profiles using a combination of statistical approaches. The interested bacterial species in the gel were cut and sequenced and were subsequently quantified and confirmed with real-time PCR. Meanwhile, the epithelial barrier was checked by microscopy and D-lactate analysis. Colonic flora changed early and differed significantly at 6 hours after reperfusion and then started to recover. The shifts were characterized by the increase of Escherichia coli and Prevotella oralis, and Lactobacilli proliferation together with epithelia healing.
This study shows for the first time that intestinal ischemia-reperfusion results in colonic flora dysbiosis that follows epithelia damage, and identifies the bacterial species that contribute most.
The objective of this study was to investigate the mechanical characteristics of implant–abutment interface design in a dental implant system, using nonlinear finite element analysis (FEA) method. This finite element simulation study was applied on three commonly used commercial dental implant systems: model I, the reduced-diameter 3i implant system (West Palm Beach, FL, USA) with a hex and a 12-point double internal hexagonal connection; model II, the Semados implant system (Bego, Bremen, Germany) with combination of a conical (45° taper) and internal hexagonal connection; and model III, the Brånemark implant system (Nobel Biocare, Gothenburg, Sweden) with external hexagonal connection. In simulation, a force of 170 N with 45° oblique to the longitudinal axis of the implant was loaded to the top surface of the abutment. It has been found from the strength and stiffness analysis that the 3i implant system has the lowest maximum von Mises stress, principal stress and displacement while the Brånemark implant system has the highest. It was concluded from our preliminary study using nonlinear FEA that the reduced-diameter 3i implant system with a hex and a 12-point double internal hexagonal connection had a better stress distribution, and produced a smaller displacement than the other two implant systems.
external hexagonal connection; finite element analysis; implant–abutment interface; internal hexagonal connection; nonlinear analysis
An increasing number of biological machines have been revealed to have more than two macroscopic states. Quantifying the underlying multiple-basin functional landscape is essential for understanding their functions. However, the present models seem to be insufficient to describe such multiple-state systems. To meet this challenge, we have developed a coarse grained triple-basin structure-based model with implicit ligand. Based on our model, the constructed functional landscape is sufficiently sampled by the brute-force molecular dynamics simulation. We explored maltose-binding protein (MBP) which undergoes large-scale domain motion between open, apo-closed (partially closed) and holo-closed (fully closed) states responding to ligand binding. We revealed an underlying mechanism whereby major induced fit and minor population shift pathways co-exist by quantitative flux analysis. We found that the hinge regions play an important role in the functional dynamics as well as that increases in its flexibility promote population shifts. This finding provides a theoretical explanation of the mechanistic discrepancies in PBP protein family. We also found a functional “backtracking” behavior that favors conformational change. We further explored the underlying folding landscape in response to ligand binding. Consistent with earlier experimental findings, the presence of ligand increases the cooperativity and stability of MBP. This work provides the first study to explore the folding dynamics and functional dynamics under the same theoretical framework using our triple-basin functional model.
A central goal of biology is to understand the function of the organism and its constituent parts at each of its scales of complexity. Function at the molecular level is often realized by changes in conformation. Unfortunately, experimental explorations of global motions critical for functional conformational changes are still challenging. In the present work, we developed a coarse grained triple-well structure-based model to explore the underlying functional landscape of maltose-binding protein (MBP). By quantitative flux analysis, we uncover the underlying mechanism by which the major induced fit and minor population shift pathways co-exist. Though we have previously lent credence to the assertion that dynamical equilibrium between open and minor closed conformations exist for all the free PBPs, the generality of this rule is still a matter of open debate. We found that the hinge flexibility is favorable to population shift mechanism. This finding provides a theoretical explanation of the mechanism discrepancies in PBP protein family. We also simulated the folding dynamics using this functional multi-basin model which successfully reproduced earlier protein melting experiment. This represents an exciting opportunity to characterize the interplay between folding and function, which is a long-standing question in the community. The theoretical approach employed in this study is general and can be applied to other systems.
The dysbiosis of intestinal microbiota has been established in Crohn's disease (CD), but the molecular characterization of this dysbiosis in Chinese subjects with CD remains unclear. This study aims to investigate the predominant bacterial composition of the faecal and mucosal-associated microbiota in Chinese CD patients using culture-independent techniques.
Eighteen patients with CD and 9 healthy controls were included in this study. The faeces and the intestinal mucosal tissues from the ulcerated and nonulcerated sites were subjected to bacterial community fingerprinting using denaturing gradient gel electrophoresis (DGGE). The predominant bacterial composition in the faeces and mucosa was determined with DNA sequencing and BLAST. We showed that the bacterial diversity in the faeces of CD patients was reduced compared with that in healthy controls (p<0.01). The faecal bacterial dysbiosis of the patients was characterized by an elevated abundance of γ-Proteobacteria (especially Escherichia coli and Shigella flexneri) and a reduced proportion of Bacteroidetes and Firmicutes. Five bacterial species defined the microbiota imbalance of the ulcerated mucosa in CD, including an increase in Escherichia coli, a decrease in Faecalibacterium prausnitzii, Lactobacillus coleohominis, Bacteroides sp and Streptococcus gallolyticus in the bacterial community as compared with the nonulcerated (p<0.01).
This is the first description of intestinal microbiota dysbiosis in Chinese CD patients. These results allow a better understanding of the faecal and mucosal microbiota in CD, showing a predominance of some opportunistic pathogenic bacteria and a decrease in beneficial bacterial species. The findings may provide novel insights into the pathogenesis of CD in Chinese population.
The title hydrazone compound, C15H13N3O3·CH3OH, crystallized as a methanol solvate. The hydrazone molecule has an E configuration about the C=N bond and is almost planar, with a dihedral angle between the benzene rings of 5.3 (3)°. In the crystal, the hydrazone molecules are linked via the methanol solvent molecule through N—H⋯O and O—H⋯O hydrogen bonds, so forming chains propagating along the a-axis direction.
In the title compound, C15H12I2N2O2, the dihedral angle between the benzene rings is 26.5 (3)° and the molecule has an E configuration about the C=N bond. An intramolecular O—H⋯N hydrogen bond is observed in the molecule. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, forming chains along the c axis.
In the title compound, C14H10ClN3O3, the dihedral angle between the benzene rings is 6.64 (13)°. In the crystal, molecules are linked through N—H⋯O hydrogen bonds, forming chains running along the c axis direction.
In the title compound, C15H14N2O3, the dihedral angle between the two benzene rings is 47.9 (3)°. In the crystal, molecules are linked through N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds, forming layers parallel to the ab plane.
In the title compound, C14H10BrN3O4·CH4O, the dihedral angle between the two benzene rings in the hydrazone molecule is 5.8 (3)° and an intramolecular O—H⋯N hydrogen bond generates an S(6) ring motif. An O—H⋯O hydrogen bond occurs between the hydrazone molecule and the methanol solvent molecule. In the crystal, the components are linked by intermolecular N—H⋯O hydrogen bonds, forming chains along the a axis.
In the molecule of the title compound, C15H13N3O3, an intramolecular O—H⋯N hydrogen bond influences the planarity of the conformation; the dihedral angle between the benzene rings is 11.4 (3)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds into chains in .
The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity.
The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions.
Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.
In the title compound, C15H15N3O, the dihedral angle between the pyridine and benzene rings is 36.3 (2)°. In the crystal, molecules are linked through intermolecular N—H⋯O hydrogen bonds, forming chains along the b axis.
The asymmetric unit of the title compound, C15H12I2N2O2, contains two independent molecules in which the dihedral angles between the two benzene rings are 62.4 (7) and 41.1 (7)°. Intramolecular O—H⋯N hydrogen bonds generate S(6) ring motifs in each molecule. In the crystal, molecules are linked through intermolecular N—H⋯O hydrogen bonds, forming chains along the a axis.
The asymmetric unit of the title compound, C15H12Br2N2O2, contains two independent molecules in which the dihedral angles between the benzene rings are 49.5 (7) and 66.4 (7)°. Intramolecular O—H⋯N hydrogen bonds generate S(6) ring motifs in each molecule. In the crystal, molecules are linked through intermolecular N—H⋯O hydrogen bonds, forming chains along the b axis.
In the title hydrazone compound, C15H12Cl2N2O, the dihedral angle between the two benzene rings is 12.2 (2)°. In the crystal, molecules are linked through intermolecular N—H⋯O hydrogen bonds, forming forming C(4) chains propagating in .
The title hydrazone compound, C15H13N3O3, was prepared by the condensation of 4-nitrobenzaldehyde with 2-methylbenzohydrazide in methanol. The dihedral angle between the two benzene rings is 14.8 (2)°. In the crystal, molecules are linked through intermolecular N—H⋯O hydrogen bonds, forming chains along the a axis.
The title hydrazone compound, C15H14N2O2, was prepared by the condensation of 4-hydroxybenzaldehyde with 2-methylbenzohydrazide in methanol. The dihedral angle between the two benzene rings is 42.3 (2)°. In the crystal structure, molecules are linked by intermolecular O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds, forming a three-dimensional framework.
HIV-1 protease processes the Gag and Gag-Pol polyproteins into mature structural and functional proteins, including itself, and is therefore indispensable for viral maturation1,2. The mature protease is active only as a dimer3–5 with each subunit contributing catalytic residues6. The full-length transframe region protease precursor appears to be monomeric yet undergoes maturation via intramolecular cleavage of a putative precursor dimer5,7–11, concomitant with the appearance of mature-like catalytic activity7,9. How such intramolecular cleavage can occur when the amino and carboxy termini of the mature protease are part of an intersubunit β-sheet located distal from the active site is unclear. Here we visualize the early events in N-terminal autoprocessing using an inactive mini-precursor with a four-residue N-terminal extension that mimics the transframe region protease precursor5,12. Using paramagnetic relaxation enhancement, a technique that is exquisitely sensitive to the presence of minor species13–16, we show that the mini-precursor forms highly transient, lowly populated (3–5%) dimeric encounter complexes that involve the mature dimer interface but occupy a wide range of subunit orientations relative to the mature dimer. Furthermore, the occupancy of the mature dimer configuration constitutes a very small fraction of the self-associated species (accounting for the very low enzymatic activity of the protease precursor), and the N-terminal extension makes transient intra- and intersubunit contacts with the substrate binding site and is therefore available for autocleavage when the correct dimer orientation is sampled within the encounter complex ensemble.
In the title compound, C16H15F2NO4, the dihedral angle between the three-membered ring and the quinoline ring system is 64.3 (3)°. In the crystal structure, intermolecular C—H⋯O hydrogen bonds link the molecules, forming a column running along .
DNA arrays permit rapid, large-scale screening for patterns of gene expression and simultaneously yield the expression levels of thousands of genes for samples. The number of samples is usually limited, and such datasets are very sparse in high-dimensional gene space. Furthermore, most of the genes collected may not necessarily be of interest and uncertainty about which genes are relevant makes it difficult to construct an informative gene space. Unsupervised empirical sample pattern discovery and informative genes identification of such sparse high-dimensional datasets present interesting but challenging problems.
A new model called empirical sample pattern detection (ESPD) is proposed to delineate pattern quality with informative genes. By integrating statistical metrics, data mining and machine learning techniques, this model dynamically measures and manipulates the relationship between samples and genes while conducting an iterative detection of informative space and the empirical pattern. The performance of the proposed method with various array datasets is illustrated.