Objective: To evaluate the predictive performance of ‘Diprifusor’ TCI (target-controlled infusion) system for its better application in clinical anesthesia. Methods: The predictive performance of a ‘Diprifusor’ TCI system was investigated in 27 Chinese patients (16 males and 11 females) during upper abdominal surgery under total intravenous anesthesia (TIVA) with propofol/fentanyl. Measured arterial propofol concentrations were compared with the values predicted by the TCI infusion system. Performance was determined by the median performance error (MDPE), the median absolute performance error (MDAPE), the divergence (the percentage change of the absolute PE with time), and the wobble (the median absolute deviation of each PE from the MDPE). Results: The median (range) values of 14.9% (−21.6%~42.9%) for MDPE, 23.3% (6.9%~62.5%) for MDAPE, −1.9% h−1 (−32.7%~23.0% h−1) for divergence, and 18.9% (4.2%~59.6%) for wobble were obtained from 227 samples from all patients. For the studied population, the PE did not increase with time but with increasing target propofol concentration, particularly following induction. Conclusions: The control of depth of anaesthesia was good in all patients undergoing upper abdominal surgical operation and the predictive performance of the ‘Diprifusor’ target controlled infusion system was considered acceptable for clinical purposes. But the relatively bigger wobble showed that the pharmacokinetic model is not so suitable and requires improvement.
Target-controlled infusion (TCI); ‘Diprifusor’ TCI system; Predictive performance assessment; Wobble; Infusion
We have determined the X-ray crystal structures of the NADH-dependent alcohol dehydrogenase LlAdhA from Lactococcus lactis and its laboratory-evolved variant LlAdhARE1 at 1.9 Å and 2.5 Å resolution, respectively. LlAdhARE1, which contains three amino acid mutations (Y50F, I212T, and L264V), was engineered to increase the microbial production of isobutanol (2-methylpropan-1-ol) from isobutyraldehyde (2-methylpropanal). Structural comparison of LlAdhA and LlAdhARE1 indicates that the enhanced activity on isobutyraldehyde stems from increases in the protein’s active site size, hydrophobicity, and substrate access. Further structure-guided mutagenesis generated a quadruple mutant (Y50F/N110S/I212T/L264V), whose KM for isobutyraldehyde is ~17-fold lower and catalytic efficiency (kcat/KM) is ~160-fold higher than wild-type LlAdhA. Combining detailed structural information and directed evolution, we have achieved significant improvements in non-native alcohol dehydrogenase activity that will facilitate the production of next-generation fuels such as isobutanol from renewable resources.
Alcohol dehydrogenase; Crystal structure; Site-saturation mutagenesis; Directed evolution; Isobutyraldehyde; Biofuel
Patients with Type I neurofibromatosis scoliosis with intra-canal rib head protrusion are extremely rare. Current knowledge regarding the diagnosis and treatment for this situation are insufficient. The purpose of this study is to share our experience in the diagnosis and surgical treatments for such unique deformities.
Six patients with Type I neurofibromatosis scoliosis with rib head dislocation into the spinal canal were diagnosed at our institution. Posterior instrumentation and spinal fusion without intra-canal rib head resection via a posterior-only approach was performed for deformity correction and rib head extraction. The efficacy and outcomes of the surgery were evaluated by measurements before, immediately and 24 months after the surgery using the following parameters: coronal spinal Cobb angle, apex rotation and kyphosis of the spine and the intra-canal rib head position. Post-operative complications, surgery time and blood loss were also evaluated.
Patients were followed up for at least 24 months post-operatively. The three dimensional spinal deformity was significantly improved and the intra-canal rib head was significantly extracted from the canal immediately after the surgery. At follow-up 24 months after surgery, solid fusions were achieved along the fusion segments, and the deformity corrections and rib head positions were well maintained. There were no surgery-related complications any time after the surgery.
Systematic examinations are needed to identify patients with Type I neurofibromatosis scoliosis with rib head dislocation into the canal who can be treated by posterior-only spinal fusion without rib head resection.
Neurofibromatosis; Rib Head Protrusion; Posterior Spinal Fusion
Accumulation of triglycerides (TG) in heart tissue has been associated with changes in left ventricular function. Proton magnetic resonance spectroscopy (1H-MRS) is currently the only non-invasive in vivo method to measure myocardial TG content. The primary aim of this study was to determine if these in vivo measurements are specific to myocardial TG in human subjects. Thus, in vivo
1H-MRS measurements were conducted on orthotopic heart transplant patients (n = 8) immediately before they underwent routine biopsies and ex vivo measurements were made on the endomyocardial biopsy samples. The correlation coefficient between the two measurements was 0.97, with p < 0.005, demonstrating for the first time the specificity of the in vivo measurement in human heart. From accompanying reliability experiments, the standardized typical error for the in vivo
1H-MRS method was estimated to be 7.0%, with a 95% confidence interval from 5.5 to 9.4%. These results suggest that 1H-MRS provides a specific and reliable measurement of myocardial TG content and is suitable for routine studies.
myocardial; triglycerides; spectroscopy
In this issue and in a recent issue of Cell, Vahedi et al. and Samstein et al. provide new insights into the strategies used to establish an enhancer landscape during development of cell lineages. They report that enhancer landscapes characterizing T cell lineages are pre-established and strongly influenced by environmental stimuli.
The improvement of bone ingrowth into prosthesis and enhancement of the combination of the range between the bone and prosthesis are important for long-term stability of artificial joints. They are the focus of research on uncemented artificial joints. Porous materials can be of potential use to solve these problems.
This research aims to observe the characteristics of the new porous Ti-25Nb alloy and its biocompatibility in vitro, and to provide basic experimental evidence for the development of new porous prostheses or bone implants for bone tissue regeneration.
The Ti-25Nb alloys with different porosities were fabricated using powder metallurgy. The alloys were then evaluated based on several characteristics, such as mechanical properties, purity, pore size, and porosity. To evaluate biocompatibility, the specimens were subjected to methylthiazol tetrazolium (MTT) colorimetric assay, cell adhesion and proliferation assay using acridine staining, scanning electron microscopy, and detection of inflammation factor interleukin-6 (IL-6).
The porous Ti-25Nb alloy with interconnected pores had a pore size of 200 µm to 500 µm, which was favorable for bone ingrowth. The compressive strength of the alloy was similar to that of cortical bone, while with the elastic modulus closer to cancellous bone. MTT assay showed that the alloy had no adverse reaction to rabbit bone marrow mesenchymal stem cells, with a toxicity level of 0 to 1. Cell adhesion and proliferation experiments showed excellent cell growth on the surface and inside the pores of the alloy. According to the IL-6 levels, the alloy did not cause any obvious inflammatory response.
All porous Ti-25Nb alloys showed good biocompatibility regardless of the percentage of porosity. The basic requirement of clinical orthopedic implants was satisfied, which made the alloy a good prospect for biomedical application. The alloy with 70% porosity had the optimum mechanical properties, as well as suitable pore size and porosity, which allowed more bone ingrowth.
Tumor survival is significantly correlated with the immune response of patients. IFNG plays an important role in the tumor host response and decreased IFNG expression is often observed in lung cancer. Studies have shown that CpG island hypermethylation plays a critical role in transcriptional silencing of IFNG gene expression. However, there is limited understanding regarding the molecular mechanisms of altered methylation, and whether the tumor microenvironment has any effect on DNA methylation and IFNG production. In the current study, we demonstrate that plasma and intra-cellular IFNG levels are significantly lower in lung cancer patients. Hypermethylation of the IFNG promoter in CD4+ T cells and plasma IFNG was negatively correlated. CD4+ T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. In conclusion, decreased IFNG expression of CD4+ T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. Our study suggests that interaction between lung cancer cells and CD4+ T cells induces DNMT expression and IFNG promoter hypermethylation in CD4+ T cell, which may serve as an important mechanism of tumor-induced immunosuppression.
Plasmodium vivax is the main malaria parasite in China, and China is now making efforts to eliminate malaria by 2020. Radical cure of vivax malaria is one of challenges for malaria elimination. The purpose is to evaluate the efficacy and safety of artemisinin-naphthoquine (ANQ) versus chloroquine-primaquine (CQ-PQ) in treatment of vivax malaria in Yunnan Province, China.
An open-label randomized and non-inferiority design, eligible patients with monoinfections of P. vivax were randomly assigned to receive either a total target dose of ANQ 24.5 mg/kg (naphthoquine 7 mg/kg and artemisinin 17.5 mg/kg), once a day for three days, or a total CQ dose of 24 mg base/kg, once a day for three days plus a PQ dose of 0.45 mg base/kg/day, once a day for eight days. Patients were followed up for one year. The difference in efficacy between ANQ and CQ-PQ was compared via Wilson’s test.
By day 42, the number of patients free of recurrence was 125 (98.4%; 95% Confidence interval, 94.4-99.8%) for ANQ arm and 123 (96.1%; 95%CI, 91.1-98.7%) for CQ-PQ, and non-significant (P = 0.4496). By day 365, the number was 101 (79.5%; 95%CI, 71.8-85.9%) for ANQ and 106 (82.8%; 95%CI, 75.1-88.9%) for CQ-PQ, and non-significant (P = 0.610). So the proportions of patients free of recurrence had no significant difference between ANQ and CQ-PQ groups by day 28, 42 and 365; compared with CQ-PQ, the side effect of ANQ was mild.
ANQ is non-inferior to CQ-PQ in terms of patients free of recurrence, and safer than CQ-PQ.
Plasmodium vivax; Artemisinin-naphthoquine; Efficacy; Safety
The Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene rs7756992 A/G polymorphism has been suggested to be associated with type 2 diabetes mellitus (T2DM), but the individual studies results are still controversial. To explore the association of CDKAL1 gene rs7756992 A/G polymorphism with T2DM, a meta-analysis involving 62,567 subjects from 21 separate studies was conducted. In the whole population, a significant association was found between CDKAL1 gene rs7756992 A/G polymorphism and T2DM under allelic (OR: 1.180, 95% CI: 1.130–1.230, P = 1.60 × 10−14), recessive (OR: 1.510, 95% CI: 1.380–1.660, P = 8.41 × 10−18), dominant (OR: 1.175, 95% CI: 1.109–1.246, P = 6.30 × 10−8), homozygous (OR: 1.400, 95% CI: 1.282–1.530, P = 8.02 × 10−14), and heterozygous genetic models (OR: 1.101, 95% CI: 1.040–1.166, P = 0.001). CDKAL1 gene rs7756992 A/G polymorphism was significantly associated with T2DM. The person with G allele of CDKAL1 gene rs7756992 A/G polymorphism might be predisposed to T2DM.
AIM: To investigate the relationship between increases in expression time of ABCG2 mRNA driven by cisplatin and efficacy of platinum-containing chemotherapy for gastric cancer.
METHODS: Tumor specimens and normal control tissues were collected from 78 patients with gastric cancer treated from January 2008 to December 2011. Fresh tumor tissue obtained from the surgically resected specimens was tested within 6 h. Polymerase chain reaction products were run on 2% agarose gels and analyzed under ultraviolet light after ethidium bromide staining. Increases in ABCG2 mRNA expression time were assessed after cancer cells were incubated with cisplatin, and were divided into terciles and compared in relation to clinical outcomes.
RESULTS: Among groups classified by expression time of ABCG2 mRNA, no significant differences in baseline clinical characteristics and pathological findings were detected. The median overall time was 14.2 (95%CI: 9.7-18.6), 11.4 (95%CI: 6.3-16.5) and 8.1 (95%CI: 5.4-10.8) in patients with low, intermediate and high increases in ABCG2 mRNA expression times (P < 0.05), respectively. Median survival associated with performance status and tumor node metastasis (TNM) stage showed a similar trend, with longer survival and higher risk for mortality associated with lower performance status score and TNM stage. In a multivariate analysis for survival with Cox proportional-hazards model, increased ABCG2 mRNA expression time was an independent predictor for overall survival. Overall survival was longer with increased ABCG2 mRNA expression times ≤ 0.71 than increased ABCG2 mRNA expression times > 0.71, with a hazard ratio for death of 0.855 (95%CI: 0.615-0.962, P = 0.038).
CONCLUSION: Increased ABCG2 mRNA expression time driven by cisplatin is associated with survival of gastric cancer patients, and this may help modify the therapeutic strategies.
Gastric cancer; ABCG2 mRNA expression; Cisplatin; Overall survival
Gene-distal enhancers are critical for tissue-specific gene expression, but their genomic determinants within a specific lineage at different stages of development are unknown. Here we profile chromatin state maps, transcription factor occupancy, and gene expression profiles during human erythroid development at fetal and adult stages. Comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that erythroid master regulators GATA1 and TAL1 act cooperatively within active enhancers but confer little predictive value for stage specificity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of an adult-stage expression program. Thus, the combinatorial assembly of lineage-specific master regulators and transcriptional co-regulators within developmental stage-specific enhancers determines gene expression programs and temporal regulation of transcriptional networks in a mammalian genome.
Amur ide (Leuciscus waleckii) is an economically and ecologically important cyprinid species in Northern Asia. The Dali Nor population living in the soda lake Dali Nor can adapt the extremely high alkalinity, providing us a valuable material to understand the adaptation mechanism against extreme environmental stress in teleost.
In this study, we generated high-throughput RNA-Seq data from three tissues gill, liver and kidney of L. waleckii living in the soda lake Dali Nor and the fresh water lake Ganggeng Nor, then performed parallel comparisons of three tissues. Our results showed that out of assembled 64,603 transcript contigs, 28,391 contigs had been assigned with a known function, corresponding to 20,371 unique protein accessions. We found 477, 2,761 and 3,376 differentially expressed genes (DEGs) in the gill, kidney, and liver, respectively, of Dali Nor population compared to Ganggeng Nor population with FDR ≤ 0.01and fold-change ≥ 2. Further analysis revealed that well-known functional categories of genes and signaling pathway, which are associated with stress response and extreme environment adaptation, have been significantly enriched, including the functional categories of “response to stimulus”, “transferase activity”, “transporter activity” and “oxidoreductase activity”, and signaling pathways of “mTOR signaling”, “EIF2 signaling”, “superpathway of cholesterol biosynthesis”. We also identified significantly DEGs encoding important modulators on stress adaptation and tolerance, including carbonic anhydrases, heat shock proteins, superoxide dismutase, glutathione S-transferases, aminopeptidase N, and aminotransferases.
Overall, this study demonstrated that transcriptome changes in L. waleckii played a role in adaptation to complicated environmental stress in the highly alkalized Dali Nor lake. The results set a foundation for further analyses on alkaline-responsive candidate genes, which help us understand teleost adaptation under extreme environmental stress and ultimately benefit future breeding for alkaline-tolerant fish strains.
L. waleckii; RNA-Seq; Gene expression; Adaptation
The incorporation of human APOBEC3G (hA3G) into HIV is required for exerting its antiviral activity, therefore the mechanism underlying hA3G virion encapsidation has been investigated extensively. hA3G was shown to form low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. The function of different forms of hA3G in its viral incorporation remains unclear.
In this study, we investigated the subcellular distribution and lipid raft association of hA3G using subcellular fractionation, membrane floatation assay and pulse-chase radiolabeling experiments respectively, and studied the correlation between the ability of hA3G to form the different complex and its viral incorporation. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation.
Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G.
Obstructive jaundice is a condition caused by blockage of the flow of bile out of the liver. This results in an overflow of bile and its by-products into the blood, and bile excretion from the body is incomplete. Untreated, obstructive jaundice can lead to serious infection that spreads to other parts of the body. We examined the protective effect of capillary artemisia polysaccharide on oxidative damage to the liver in growing rats with obstructive jaundice (OJ). Growing male Wistar rats (n=40, age 3–4 weeks) were randomly divided into four groups (n=10 in each group): normal control group, sham group, OJ group and OJ with capillary artimesia polysaccha-ride treatment group (study group). The rats of the OJ group and the study group were subjected to common bile dust ligation, while the sham group had the bile duct mobilized but not ligated. The rats of the study group recieved 5 ml/kg capillary artimesia polysaccharide (0.5 g/ml) by intraperitoneal (i.p.) injection once daily while the other groups were administered 5 ml/kg saline by i.p. injection. After 4 weeks, the rats were sacrificed to obtain liver weight and to compute the liver coefficient. Additional measures included liver homogenate malondialdehyde (MDA) and the activity levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The liver weight and liver coefficient of rats in the study group were lower than those in the OJ group and higher than those in the control and sham groups (P<0.05). Liver homogenate MDA content in the study group rats was lower than that in the OJ group and higher than that in the control and sham group (P<0.05). SOD, GSH-Px and CAT activities were higher in the study group rats than those in the OJ group and lower than those in other groups (P<0.05). Capillary artimesia capillary artemisia polysaccharide protects the liver from oxidative damage and improves antioxidant defense in growing rats with obstructive jaundice.
capillary artimesia; obstructive jaundice; oxidative damage; polysaccharide
Human bocavirus 1 (HBoV1) is an emerging human-pathogenic respiratory virus. We characterized two important features of HBoV1 infection in polarized primary human airway epithelia (HAE). Apical HBoV1 infection of HAE at a low multiplicity of infection causes disruption of the tight junction barrier, loss of cilia, and epithelial cell hypertrophy, which are hallmarks of the airway epithelial damage caused by HBoV1 infection. HBoV1 also infects HAE from the basolateral surface productively, although less efficiently, and this also leads to the characteristic airway epithelial damage.
Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. The enhanced nitrative stress plays an important role in homocysteine-induced endothelial dysfunction. Previous studies have showed that phytoestrogen α-zearalanol alleviated endothelial injury in ovariectomized hyperhomocysteinemic rats; however, the underlying mechanism remains to be clarified. This study was to investigate the effects of α-zearalanol on homocysteine-induced endothelial apoptosis in vitro and explore the possible role of nitrative stress in these effects. Results showed that homocysteine (500 μmol/L, 24 h) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) obviously, and this effect was significantly attenuated by pretreatment with α-zearalanol (10−8~10−6 mol/L). Moreover, α-zearalanol downregulated proapoptotic protein Bax, upregulated antiapoptotic proteins Bcl-2 and Bcl-XL, and decreased the expression and activity of caspase-9. These findings demonstrated that α-zearalanol could effectively alleviate homocysteine-induced endothelial apoptosis, and this antiapoptosis effect might be related to the inhibition of the intrinsic pathway. Western blot indicated an enhanced 3-nitrotyrosine expression in HUVECs when challenged with homocysteine, which was attenuated by pretreatment with α-zearalanol. This result implied that inhibition of nitrative stress might play a role in the protective effect of α-zearalanol on endothelial cells. Such discovery may shed a novel light on the antiatherogenic activities of α-zearalanol in hyperhomocysteinemia.
The aim of this study was to investigate the association between signal transducer and activator of transcription 3 (STAT3) polymorphisms and autoimmune thyroid diseases and clinical features. We genotyped six single-nucleotide polymorphisms (SNPs) rs1053005, rs2293152, rs744166, rs17593222, rs2291281, and rs2291282 of STAT3 gene in 667 patients with autoimmune thyroid disease (417 Graves’ disease (GD) and 250 Hashimoto’s thyroiditis (HT)) and 301 healthy controls. The allele A from rs1053005 was significantly less frequent in both GD and HT patients (P = 0.0024, OR = 0.6958, 95%CI = 0.5508–0.8788; P = 0.0091, OR = 0.7013, 95%CI = 0.5397–0.9112, respectively). The AA genotype of rs1053005 was less in GD and HT patients too (P = 0.0025,OR = 0.6278, 95%CI = 0.466–0.847) and (P = 0.0036,OR = 0.601, 95%CI = 0.428–0.843). The allele G from rs17593222 increased the susceptibility to the ophthalmopathy development both in autoimmune thyroid disease (AITD) and GD patients (P = 0.0007, OR = 3.980, 95%CI = 1.871–8.464; P = 0.0081, OR = 3.378, 95%CI = 1.441–7.919, respectively). The allele A and AA genotype of SNP rs1053005 may protect individuals from the susceptibility to AITD and their frequency decreased in AITD patients. In addition, the allele G of rs17593222 may increase the ophthalmopathy risk in AITD patients. Our findings suggest the existence of association between STAT3 gene and AITD, thus adding STAT3 gene to the list of the predisposing genes to AITD.
Signal transducer and activator of transcription 3 (STAT3); Single-nucleotide polymorphisms (SNPs); Autoimmune thyroid disease; Graves’ disease; Hashimoto’s thyroiditis
A new approach, the projective system approach, is proposed to realize modified projective synchronization between two different chaotic systems. By simple analysis of trajectories in the phase space, a projective system of the original chaotic systems is obtained to replace the errors system to judge the occurrence of modified projective synchronization.
Theoretical analysis and numerical simulations show that, although the projective system may not be unique, modified projective synchronization can be achieved provided that the origin of any of projective systems is asymptotically stable. Furthermore, an example is presented to illustrate that even a necessary and sufficient condition for modified projective synchronization can be derived by using the projective system approach.
To investigate the relationship between the level of left renal vein (LRV) compression and changes in the perfusion of the left kidney in patients with nutcracker syndrome (NCS) by one-stop whole-organ perfusion imaging of bilateral kidneys using 640-slice volume CT.
Twelve patients, clinically diagnosed with NCS, were subjected to one-stop examination of kidneys. Angiography and whole-organ perfusion imaging of bilateral kidneys were conducted, and the compression segment of LRV was demonstrated and measured. Information including the results of whole-organ perfusion images of both kidneys in 12 patients was collected. Results of epigastrium dynamic volume scanning by 640-slice volume CT were collected for 12 patients as control group. Left and right renal cortexes were chosen as regions of interest (ROI), and their perfusion values were measured.
The perfusion values of the left and right renal cortexes in the control group were 323.8 ml·min−1·100 ml−1 and 322.9 ml·min−1·100 ml−1, respectively. The difference was not statistically significant (t = 1.388, P = 0.193). For NCS patients, the perfusion values of the left and right renal cortexes were 350.8 ml·min−1·100 ml−1 and 391.1 ml·min−1·100 ml−1, respectively. Significantly decreased value was observed in left renal cortex compared to that of the right renal cortex, with the mean decrease of 40.3 ml·min−1·100 ml−1, and the difference was statistically significant (t = −4.204, P = 0.001).
As a non-invasive functional imaging technique, whole-organ perfusion imaging of kidneys can be used to evaluate the organ and tissue perfusion status and to accurately reflect the hemodynamic changes of the left renal cortex in the patients with NCS. Whole organ perfusion imaging may also provide the basis for quantitative diagnosis and clinical interventions of NCS.
SARI is associated with the risk for several cancers, and loss of SARI expression is frequently found in aggressive and metastatic cancer. Limited evidence shows that SARI is a tumor suppressor gene, but the role of SARI in non-small cell lung cancer (NSCLC) has not been previously reported. This study was to investigate the SARI expression profile in surgically resected lung cancer tissues of Chinese patients by immunohistochemistry and evaluate the relationship between SARI expression and prognosis of lung cancer patients. Furthermore, SARI gene was transfected into lung cancer cells (A549), and the growth curve and cell healing of lung cancer cells were determined, aiming to investigate the influence of SARI on the growth and migration of lung cancer cells in vitro. Results showed that 103 of 195 (52.82%) tissues were positive for SARI. When compared with normal tissues, SARI expression significantly reduced in 50.26% of NSCLC tissues. Patients with negative or reduced SARI expression were more likely to have advanced lung cancer and lymph node metastasis. In squamous carcinoma and adenocarcinoma patients, the SARI expression had no relation with the survival time; However in one-on-one analysis SARI expression in tumor cells and adjacent tissues, patients which tumor cells SARI express reduced than adjacent tissues, survival time was significantly shorter than those without reduction in SARI expression (Log Rank test, p = 0.001). After transfection by SARI gene, the proliferation and migration of A549 cells were obviously inhibited (p < 0.001). These results demonstrate that decreased SARI expression may predict a poor prognosis in NSCLC patients, and SARI may serve as a prognostic biomarker and potential therapeutic target for lung cancer.
SARI; non-small cell lung cancer; prognosis; surgically resected cancer
AIM: To investigate the clinical advantages of the stent-laparoscopy approach to treat colorectal cancer (CRC) patients with acute colorectal obstruction (ACO).
METHODS: From April 2008 to April 2012, surgery-related parameters, complications, overall survival (OS), and disease-free survival (DFS) of 74 consecutive patients with left-sided CRC presented with ACO who underwent self-expandable metallic stent (SEMS) placement followed by one-stage open (n = 58) or laparoscopic resection (n = 16) were evaluated retrospectively. The stent-laparoscopy group was also compared with a control group of 96 CRC patients who underwent regular laparoscopy without ACO between January 2010 and December 2011 to explore whether SEMS placement influenced the laparoscopic procedure or reduced long-term survival by influencing CRC oncological characteristics.
RESULTS: The characteristics of patients among these groups were comparable. The rate of conversion to open surgery was 12.5% in the stent-laparoscopy group. Bowel function recovery and postoperative hospital stay were significantly shorter (3.3 ± 0.9 d vs 4.2 ± 1.5 d and 6.7 ± 1.1 d vs 9.5 ± 6.7 d, P = 0.016 and P = 0.005), and surgical time was significantly longer (152.1 ± 44.4 min vs 127.4 ± 38.4 min, P = 0.045) in the stent-laparoscopy group than in the stent-open group. Surgery-related complications and the rate of admission to the intensive care unit were lower in the stent-laparoscopy group. There were no significant differences in the interval between stenting and surgery, intraoperative blood loss, OS, and DFS between the two stent groups. Compared with those in the stent-laparoscopy group, all surgery-related parameters, complications, OS, and DFS in the control group were comparable.
CONCLUSION: The stent-laparoscopy approach is a feasible, rapid, and minimally invasive option for patients with ACO caused by left-sided CRC and can achieve a favorable long-term prognosis.
Self-expandable metallic stent; Colorectal cancer; Endoscopy; Laparoscopy; Efficiency; Safety
The Gram-negative bacteria type VI secretion system (T6SS) has been found to play an important role in interbacterial competition, biofilm formation and many other virulence-related processes. The bacteria harboring T6SS inject the effectors into their recipient’s cytoplasm or periplasm to kill them and meanwhile, to avoid inhibiting itself, the cognate immunity proteins were produced to acts as the effector inhibitor. Tae4 (type VI amidase effector 4) and Tai4 (type VI amidase immunity 4) are newly identified T6SS effector-immunity (EI) pairs. We have recently solved the structures of StTae4-Tai4 and EcTae4-Tai4 complexes from the human pathogens Salmonella typhimurium and Enterobacter cloacae, respectively. It is very interesting and important to discover whether there is cross-neutralization between St- and EcTai4 and whether their effector inhibition mechanism is conserved. Here, we determined the crystal structure of StTae4 in complex with EcTai4. The solution conformation study revealed it is a compact heterotetramer that consists of an EcTai4 homodimer binding two StTae4 molecules in solution, different from that in crystal. A remarkable shift can be observed in both the flexible winding loop of StTae4 and protruding loop of EcTai4 and disulfide bonds are formed to stabilize their overall conformations. The in vitro and in vivo interactions studies showed EcTai4 can efficiently rescue the cells from the toxicity of its cognate effectors StTae4, but can not neutralize the toxic activities of the effectors from other families. These findings provide clear structural evidence to support the previous observation of cross-immunity within T6SS families and provide a basis for understanding their important roles in polymicrobial environments.
To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren-Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T.
Materials and Methods
30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-Organ MR Imaging Score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA.
Lateral (72±10 milliseconds, median ± interquartile range) and medial (65±10 milliseconds) femoral anterior cartilage subregions in moderate-severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful-minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate-severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful-minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal).
T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with osteoarthritis.
MRI; Cartilage; T1rho mapping; Meniscus; Osteoarthritis
In Huntington's disease (HD), the mutant huntingtin (mhtt) protein is associated with striatal dysfunction and degeneration. Excitotoxicity and early synaptic defects are attributed, in part, to altered NMDA receptor (NMDAR) trafficking and function. Deleterious extrasynaptic NMDAR localization and signalling are increased early in yeast artificial chromosome mice expressing full-length mhtt with 128 polyglutamine repeats (YAC128 mice). NMDAR trafficking at the plasma membrane is regulated by dephosphorylation of the NMDAR subunit GluN2B tyrosine 1472 (Y1472) residue by STriatal-Enriched protein tyrosine Phosphatase (STEP). NMDAR function is also regulated by calpain cleavage of the GluN2B C-terminus. Activation of both STEP and calpain is calcium-dependent, and disruption of calcium homeostasis occurs early in the HD striatum. Here, we show increased calpain cleavage of GluN2B at both synaptic and extrasynaptic sites, and elevated extrasynaptic total GluN2B expression in the YAC128 striatum. Calpain inhibition significantly reduced extrasynaptic GluN2B expression in the YAC128 but not wild-type striatum. Furthermore, calpain inhibition reduced whole-cell NMDAR current and the surface/internal GluN2B ratio in co-cultured striatal neurons, without affecting synaptic GluN2B localization. Synaptic STEP activity was also significantly higher in the YAC128 striatum, correlating with decreased GluN2B Y1472 phosphorylation. A substrate-trapping STEP protein (TAT-STEP C-S) significantly increased VGLUT1-GluN2B colocalization, as well as increasing synaptic GluN2B expression and Y1472 phosphorylation. Moreover, combined calpain inhibition and STEP inactivation reduced extrasynaptic, while increasing synaptic GluN2B expression in the YAC128 striatum. These results indicate that increased STEP and calpain activation contribute to altered NMDAR localization in an HD mouse model, suggesting new therapeutic targets for HD.