AIM: To develop a pharmacodynamic model of portal hypertension from chronic hepatitis.
METHODS: Pathological changes and collagen depositions were analyzed using morphometry to confirm CCl4-induced chronic hepatitis. At d0, d28, d56 and d84 of the process, the portal perfused velocities (μL/min) in isolated rat livers were exactly controlled with a quantified pump. The pressure (mmHg) was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume (300 mL) of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetylcholine were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.
RESULTS: At d0, d28, d56 and d84, the equations of portal pressure potency from the concentrations of phenylephrine used to constrict the portal vein in isolated perfused rat livers were Y = 0.1732 + 0.3970/[1 + 10(-4.3061-0.4407 X)], Y = -0.004934 + 0.12113/[1 + 10(-3.1247-0.3262 X)], Y = 0.0104 + 0.2643/[1 + 10(-8.8462-0.9579 X)], and Y = 0.01603 + 0.12107/[1 + 10(-5.1134-0.563 X)]; the median effective concentrations were 1.69 × 10-10 mol/L, 2.64 × 10-10 mol/L, 5.82 × 10-10 mol/L, and 8.24 × 10-10 mol/L, respectively. The equations from the concentrations of acetylcholine used to relax the portal vein were Y = -0.4548 + 0.3274/[1 + 10(6.1538 + 0.5554 X)], Y = -0.05391 + 0.06424/[1 + 10(3.8541 + 0.3469 X)], Y = -0.2733 + 0.22978/[1 + 10(3.0472 + 0.3008 X)], and Y = -0.0559 + 0.053178/[1 + 10(5.6336 + 0.5883 X)]; the median effective concentrations were 8.40 × 10-10 mol/L, 7.73 × 10-12 mol/L, 5.98 × 10-11 mol/L, and 2.66 × 10-10 mol/L, respectively.
CONCLUSION: A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concentrations of phenylephrine and acetylcholine.
Chronic hepatitis; Isolated portal perfused rat liver; Pharmacodynamic model; Portal hypertension
Rapid response to chemotherapy in metastatic colorectal cancer (mCRC) patients (response within 12 weeks of chemotherapy) may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs) in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens.
Materials and Methods
Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658). The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing
Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively). The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002). Their significances were all maintained even after multiple testing (all pc < 0.05). The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS) (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037). None of the SNPs predicted overall survival.
Polymorphisms of solute carriers’ may be useful to predict rapid response to irinotecan plus fluoropyrimidine and PFS in mCRC patients.
The Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) has been reported to have both tumor-promoting and tumor-suppressing roles in tumorigenesis. However, the role of SHP-2 in tumor immunity remains unclear. Here we observed progressively lower levels of phosphorylated SHP-2 in tumor-associated CD4+ T cells during melanoma development in a murine model. Similarly, the levels of phosphorylated SHP-2 in the CD4+ T cells of human melanoma specimens revealed a decrease paralleling cancer development. The CD4+ T cell-specific deletion of SHP-2 promoted melanoma metastasis in mice. Furthermore, SHP-2 deficiency in CD4+ T cells resulted in the increased release of inflammatory cytokines, especially IL-6, and the enhanced accumulation of tumor-promoting myeloid-derived suppressor cells (MDSCs) in tumor-bearing mice. An IL-6-neutralizing antibody reduced MDSC accumulation and inhibited tumor growth in CD4+ T-cell-specific SHP-2-knockout mice. Our results suggest that SHP-2 in CD4+ T cells plays an important role in preventing melanoma progression and metastasis.
AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis.
METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.
RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads.
CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.
Chronic hepatitis; Portal hypertension; Isolated portal perfused rat liver; Diammonium glycyrrhizinate; Inducible nitric oxide synthase
Influence of fish oil supplementation on postoperative atrial fibrillation (POAF) was inconsistent according to published clinical trials. The aim of the meta-analysis was to evaluate the effects of perioperative fish oil supplementation on the incidence of POAF after cardiac surgery.
Pubmed, Embase and the Cochrane Library databases were searched. Randomized controlled trials (RCTs) assessing perioperative fish oil supplementation for patients undergoing cardiac surgery were identified. Data concerning study design, patient characteristics, and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models.
Eight RCTs involving 2687 patients were included. Perioperative supplementation of fish oil did not significantly reduce the incidence of POAF (RR = 0.86, 95%CI 0.71 to 1.03, p = 0.11) or length of hospitalization after surgery (WMD = 0.10 days, 95% CI: 0.48 to 0.67 days, p = 0.75). Fish oil supplementation also did not affect the perioperative mortality, incidence of major bleeding or the length of stay in the intensive care unit. Meta-regression and subgroup analyses indicated mean DHA dose in the supplements may be a potential modifier for the effects of fish oil for POAF. For supplements with DHA >1 g/d, fish oil significantly reduced the incidence of POAF; while it did not for the supplements with a lower dose of DHA.
Current evidence did not support a preventative role of fish oil for POAF. However, relative amounts of DHA and EPA in fish oil may be important for the prevention of POAF.
In the present work, we investigate the effect of “fatigue” on the fatigue behavior and atomic structure of Zr-based BMGs. Fatigue experiments on the failed-by-fatigue samples indicate that the remnants generally have similar or longer fatigue life than the as-cast samples. Meanwhile, the pair-distribution-function (PDF) analysis of the as-cast and post-fatigue samples showed very small changes of local atomic structures. These observations suggest that the fatigue life of the 6-mm in-diameter Zr-based BMG is dominated by the number of pre-existing crack-initiation sites in the sample. Once the crack initiates in the specimen, the fatigue-induced damage is accumulated locally on these initiated sites, while the rest of the region deforms elastically. The results suggest that the fatigue failure of BMGs under compression-compression fatigue experiments is a defect-controlled process. The present work indicates the significance of the improved fatigue resistance with decreasing the sample size.
Previous genome-wide association study by WTCCC identified many susceptibility loci of common autoimmune diseases in British, including rheumatoid arthritis (RA). Because of the genetic heterogeneity of RA, it is necessary to replicate these susceptibility loci in other populations. Here, three SNPs with strong RA association signal in the British were analyzed in Han Chinese, and two SNPs (rs6457617 and rs11761231) were genotyped in the test cohort firstly. The rs6457617 was significantly associated with RA in the test cohort. The individuals bearing the homozygous genotype CC had 0.39-fold risk than these bearing the wild-type genotype TT (P = 0.004, OR 0.39, [95% CI 0.21–0.74]). And the protective effect of allele C was confirmed in another validation cohort with 1514 samples (Pgenotye CC/TT = 5.9 × 10−10, OR 0.34, [95% CI 0.24–0.48]). The rs6457617 can be used as a tagSNP of HLA-DQA1∗03 which encoded MHC-II α chain. Since MHC restriction is important for primary T-cells in positive selection and negative selection stages, MHC protein polymorphisms may be implicated in shaping the T-cell repertoire, including the emergence of a T-cell clone involved in the inflammatory arthritis.
The association of functional polymorphisms in the promoter of the apoptosis gene FAS with systemic lupus erythematosus (SLE) susceptibility has been a controversial subject. We conducted a case-control study to investigate this association in a Chinese population and performed a meta-analysis in different populations. The single nucleotide polymorphisms (SNPs) rs2234767 (−1377G>A) and rs1800682 (−670A>G) were genotyped by TaqMan allelic discrimination assays in 552 Chinese SLE patients and 718 healthy controls. In our case-control study, we observed allelic association between the promoter SNP rs2234767 [P=0.033, odds ratio (OR)=0.836, 95% confidence interval (CI), 0.709–0.986] and SLE but not the SNP rs1800682. Haplotype analysis revealed that one haplotype of GA was significantly associated with the disease (P=0.039, OR=1.184, 95% CI, 1.009–1.391). In the meta-analysis available studies, including our data, were combined using the STATA software package v.7.0. The meta-analysis revealed a significant association between FAS polymorphisms and SLE (rs2234767 A vs. G allele; P=0.004, OR=0.819, 95% CI, 0.715–0.938, rs1800682 G vs. A allele: P=0.034, OR=0.791, 95% CI, 0.637–0.983). In conclusion, FAS gene polymorphisms may contribute to SLE susceptibility in the Chinese population, and the meta-analysis shows that FAS polymorphisms may be associated with SLE susceptibility in different populations.
systemic lupus erythematosus; FAS; single-nucleotide polymorphisms; meta-analysis
Only a few investigations were based on limb bone density. This study evaluated the efficacy of soy isoflavone in the treatment of the principal menopausal disorders, limb bone density and the role of pathway. The research protocol involved the random subdivision of the enrolled sample into two groups of 40 women, who were to receive treatment for 6 months with isoflavone (90 mg/day) and with placebo. All of the patients were asked to fill in a questionnaire concerning their complaints. BMD of the radius and tibia were measured using quantitative ultrasound. Bone metabolism indexes calcium, phosphorus and alkaline phosphatase (ALP) were examined regularly. Serum cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) examined by ELISA. The results of the score of Kupperman table showed that the isoflavone can lead to a significant reduction in some of the disorders. Compared with placebo, the tibia bone density in isoflavone group increased obviously against the base value before trail. Isoflavone led to a stronger descent of the concentration of ALP and a decrease of IL-6 and TNF-α level than placebo. For climacteric women, soy isoflavone in the dose of 90 mg/day could improve some menopausal syndromes and was effective on increasing limb bone density, which maybe had the relationship with the levels of IL-6, TNF-α and ALP in serum.
soy isoflavone; climacteric women; bone mineral density; serum cytokines; bone metabolism indexes
A series of diaryl amines, ethers and thioethers were synthesized under microwave irradiation efficiently at presence of KF/Al2O3 in 83%–96% yields without any solvent. The salient characters of this method lie in short reaction time, high yields, general applicability to substrates and simple workup procedure. At the same time, their antifungal biological activities against six phytopathogen were evaluated. Most of the compounds (3b, 3c, 3g–o) are more potent than thiophannate-methyl against to Magnaporthe oryzae. This implies that diaryl amine or ether moiety may be helpful in finding a fungicide against Magnaporthe oryzae.
microwave-assisted organic synthesis; diaryl amine; diaryl ether; KF/Al2O3
Peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) is involved in the process of tumorigenesis. The two single nucleotide polymorphisms (−677T>C, −842G>C) in the PIN1 promoter region have been suspected of being associated with cancer risk for years, but the conclusion is still inconclusive.
Eligible case-control studies were retrieved by searching databases and references of related reviews and studies. Genotype distribution data, adjusted odds ratios (ORs) and 95% confidence (CIs) intervals were extracted to calculate pooled ORs.
A total of 4619 cancer cases and 4661 controls were included in this meta-analysis. Overall, the PIN1 −667T>C polymorphism was not associated with cancer risk, while the −842C allele was significantly associated with reduced cancer risk (CC+GC vs. GG, OR = 0.725, 95% CI: 0.607–0.865; Pheterogeneity = 0.012 and GC vs. GG: OR = 0.721, 95% CI: 0.591–0.880; Pheterogeneity = 0.003). Results from genotype distribution data were in agreement with those calculated with adjusted ORs and 95% CIs. No publication bias was detected.
Results of this meta-analysis suggest that the PIN1 −842G>C polymorphism is associated with decreased cancer risk, but that the −667T>C polymorphism is not.
The disease burden of children with laboratory-confirmed influenza in China has not been well described. The aim of this study was to understand the epidemiology and socio-economic burden of influenza in children younger than 5 years in outpatient and emergency department settings.
A prospective study of laboratory-confirmed influenza among children presenting to the outpatient settings in Soochow University Affiliated Children's Hospital with symptoms of influenza-like illness (ILI) was performed from March 2011 to February 2012. Throat swabs were collected for detection of influenza virus by reverse transcription polymerase chain reaction assay. Data were collected using a researcher administered questionnaire, concerning demographics, clinical characteristics, direct and indirect costs, day care absence, parental work loss and similar respiratory illness development in the family.
Among a total of 6,901 children who sought care at internal outpatient settings, 1,726 (25%) fulfilled the criteria of ILI and 1,537 were enrolled. Influenza was documented in 365 (24%) of enrolled 1,537 ILI cases. Among positive patients, 52 (14%) were type A and 313 (86%) were type B. About 52% of influenza outpatients had over-the-counter medications before physician visit and 41% visited hospitals two or more times. Children who attended daycare missed an average of 1.9 days. For each child with influenza-confirmed disease, the parents missed a mean of 1.8 work days. Similar respiratory symptoms were reported in 43% of family contacts of influenza positive children after onset of the child's illness. The mean direct and indirect costs per episode of influenza were $123.4 for outpatient clinics and $134.6 for emergency departments, and $125.9 for influenza A and $127.5 for influenza B.
Influenza is a common cause of influenza-like illness among children and has substantial socio-economic impact on children and their families regarding healthcare seeking and day care/work absence. The direct and indirect costs of childhood influenza impose a heavy financial burden on families. Prevention measures such as influenza vaccine could reduce the occurrence of influenza in children and the economic burden on families.
Despite rapid progress in understanding the mechanisms that shape the evolution of proteins, the relative importance of various factors remain to be elucidated. In this study, we have assessed the effects of 16 different biological features on the evolutionary rates (ERs) of protein-coding sequences in bacterial genomes.
Our analysis of 18 bacterial species revealed new correlations between ERs and constraining factors. Previous studies have suggested that transcriptional abundance overwhelmingly constrains the evolution of yeast protein sequences. This transcriptional abundance leads to selection against misfolding or misinteractions. In this study we found that there was no single factor in determining the evolution of bacterial proteins. Not only transcriptional abundance (codon adaptation index and expression level), but also protein-protein associations (PPAs), essentiality (ESS), subcellular localization of cytoplasmic membrane (SLM), transmembrane helices (TMH) and hydropathicity score (HS) independently and significantly affected the ERs of bacterial proteins. In some species, PPA and ESS demonstrate higher correlations with ER than transcriptional abundance.
Different forces drive the evolution of protein sequences in yeast and bacteria. In bacteria, the constraints are involved in avoiding a build-up of toxic molecules caused by misfolding/misinteraction (transcriptional abundance), while retaining important functions (ESS, PPA) and maintaining the cell membrane (SLM, TMH and HS). Each of these independently contributes to the variation in protein evolution.
Evolutionary rates; Bacteria; Multiple features; Transcriptional abundance
The aim of this study was to evaluate the status of HER2 protein expression in patients with renal cell carcinoma (RCC) and to determine its prognostic significance. A total of 42 paraffin-embedded tumor tissues and 42 additional corresponding adjacent normal tissues from RCC patients were randomly collected and studied using immunohistochemistry (IHC). Protein samples of 6 fresh specimens from tumor and adjacent normal tissues obtained during surgery were extracted and tested using western blotting to confirm the IHC results. Of the 42 tumor tissues and adjacent normal tissues tested, IHC showed that 7 tumors (16.67%) and 33 adjacent normal tissues (78.57%) expressed the HER2 protein. In addition, results of the western blotting revealed weak HER2 reactivity in primary tumor cells in two of 6 specimens obtained during surgery. All 6 normal tissues showed positive expression, which was in accordance with the outcome of IHC. In conclusion, HER2 is frequently expressed in normal renal tissues and rarely expressed in RCC tissues. Furthermore, the HER2 status of normal tissue is negatively correlated with that of the RCC tissues (r=−0.410, P=0.007) and the TNM stage (r=−0.246, P=0.027), suggesting that HER2 is involved in RCC oncogenesis.
HER2; renal cell carcinoma; TNM stage
The major histocompatibility complex (MHC) is one of the most variable and gene-dense regions of the human genome. Most studies of the MHC, and associated regions, focus on minor variants and HLA typing, many of which have been demonstrated to be associated with human disease susceptibility and metabolic pathways. However, the detection of variants in the MHC region, and diagnostic HLA typing, still lacks a coherent, standardized, cost effective and high coverage protocol of clinical quality and reliability. In this paper, we presented such a method for the accurate detection of minor variants and HLA types in the human MHC region, using high-throughput, high-coverage sequencing of target regions. A probe set was designed to template upon the 8 annotated human MHC haplotypes, and to encompass the 5 megabases (Mb) of the extended MHC region. We deployed our probes upon three, genetically diverse human samples for probe set evaluation, and sequencing data show that ∼97% of the MHC region, and over 99% of the genes in MHC region, are covered with sufficient depth and good evenness. 98% of genotypes called by this capture sequencing prove consistent with established HapMap genotypes. We have concurrently developed a one-step pipeline for calling any HLA type referenced in the IMGT/HLA database from this target capture sequencing data, which shows over 96% typing accuracy when deployed at 4 digital resolution. This cost-effective and highly accurate approach for variant detection and HLA typing in the MHC region may lend further insight into immune-mediated diseases studies, and may find clinical utility in transplantation medicine research. This one-step pipeline is released for general evaluation and use by the scientific community.
In the title molecule, C22H16O, the indanone ring system is approximately planar with a dihedral angle between the fused rings of 5.13 (14)°. Two benzene rings are linked together at one side of a double bond, sitting on either side of the indanone ring system and making dihedral angles of 70.30 (12) and 44.74 (13)° with it. In the crystal, hydrogen bonding is not present, but weak C—H⋯π or π–π interactions occur and molecules form a sheet-like structure in the bc plane.
This study presented the performance of simultaneous nitrification and denitrification (SND) process using a new developed hybrid airlift reactor which integrated the activated sludge reaction process in the airlift reactor and the sludge settling separation process in the clarifier. The proposed reactor was started up successfully after 76 days within which the COD and total nitrogen removal rate can reach over 90% and 76.3%, respectively. The effects of different COD/N and DO concentrations on the performance of reactor were investigated. It was found that the influent COD/N maintained at 10 was sufficient for SND and the optimum DO concentration for SND was in the range of 0.5 to 0.8 mg L−1. Batch test demonstrated that both macroscopic environment caused by the spatial DO concentration difference and microscopic environment caused by the stratification of activated sludge may be responsible for the SND process in the reactor. The hybrid airlift reactor can accomplish SND process in a single reactor and in situ automatic separation of sludge; therefore, it may serve as a promising reactor in COD and nitrogen removal fields.
In previous randomized trials, transarterial chemoembolization (TACE) has shown an improvement of survival rate in hepatocellular carcinoma (HCC) when combined with radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or other therapies. The aim of this meta-analysis was to evaluate the effectiveness of combination therapy of TACE with RFA, PEI, radiotherapy (RT), three-dimensional conformal radiation therapy (3D-CRT) or High-Intensity Focused Ultrasound (HIFU).
Randomized or nonrandomized studies comparing TACE combined with RFA, PEI, RT, 3D-CRT or HIFU with TACE alone for HCC were included. Meta-analysis was performed using a fix-effects model in RCTs and a random-effects model among the observational studies.
10 randomized trials and 18 observational studies matched the selection criteria, including 2497 patients (682 in RCTs, 1815 in non-RCTs). Meta-analysis of RCTs showed that the combination of TACE and PEI ((RR)1-year=1.10, 95%CI=0.99-1.22, p=0.073; (RR)3-year=2.32, 95%CI=1.52-3.53, p<0.001), TACE+RT ((RR)1-year=1.37, 95%CI=1.11-1.70, p=0.004; (RR)3-year=2.32, 95%CI=1.44-3.75, p=0.001) were associated with higher survival rates. The results of observational studies were in good consistency with that of RCTs. Furthermore, TACE plus 3D-CRT ((RR)1-year=1.22, 95%CI=1.06-1.41, p=0.005; (RR)3-year=2.05, 95%CI=1.48-2.84, p<0.001) and TACE plus HIFU ((RR)1-year=1.16, 95%CI=1.01-1.33, p=0.033; (RR)3-year=1.66, 95%CI=1.12-2.45, p=0.011) have introduced marked survival benefit when pooling results from observational studies.
This meta-analysis demonstrated that TACE combined with local treatments, especially PEI, HIFU or 3D-CRT could improve the overall survival status than performing TACE alone. Importantly, these results need to be validated in further high-quality clinical trials.
Background. Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP. Methods and Results. Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ⩽30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect.
As a useful tool for geographical cluster detection of events, the spatial scan statistic is widely applied in many fields and plays an increasingly important role. The classic version of the spatial scan statistic for the binary outcome is developed by Kulldorff, based on the Bernoulli or the Poisson probability model. In this paper, we apply the Hypergeometric probability model to construct the likelihood function under the null hypothesis. Compared with existing methods, the likelihood function under the null hypothesis is an alternative and indirect method to identify the potential cluster, and the test statistic is the extreme value of the likelihood function. Similar with Kulldorff’s methods, we adopt Monte Carlo test for the test of significance. Both methods are applied for detecting spatial clusters of Japanese encephalitis in Sichuan province, China, in 2009, and the detected clusters are identical. Through a simulation to independent benchmark data, it is indicated that the test statistic based on the Hypergeometric model outweighs Kulldorff’s statistics for clusters of high population density or large size; otherwise Kulldorff’s statistics are superior.
In this study, the functional role of INSM1 is examined with an AR42J acinar cell model for trans-differentiation into insulin-positive cells. Islet transcription factors (ITFs: INSM1, Pdx-1, and NeuroD1) are over-expressed in AR42J cells using adenoviral vectors. Addition of Ad-INSM1 alone or the combination of three ITFs to the AR42J cells triggers cellular trans-differentiation. Ectopic expression of INSM1 directly induces insulin, Pax6, and Nkx6.1 expression, whereas Pdx-1 and NeuroD1 were slightly suppressed by INSM1. Addition of Pdx-1 and NeuroD1 with INSM1 further enhances endocrine trans-differentiation by increasing both the numbers and intensity of the insulin positive cells with simultaneous activation of ITFs, Ngn3 and MafA. INSM1 expression alone partially inhibits dexamethasone-induced exocrine amylase expression. The combination of the three ITFs completely inhibits amylase expression and concomitantly induces greater acinar cell trans-differentiation into endocrine cells. Also, addition of the three ITFs promotes EGF and TGFβ receptors expression. Stimulation by the three ITFs along with the EGF/TGFβ growth factors strongly promotes insulin gene expression. The combination of the three ITFs and EGF/TGFβ growth factors with the primary cultured pancreatic acini also facilitates exocrine to endocrine cell differentiation. Taken together, both the AR42J cell line and the primary cultured mouse acinar cells support INSM1 induced acini trans-differentiation model.
INSM1; AR42J; islet transcription factor; acinar cells; trans-differentiation; reprogramming
The aim of this study was to investigate the method of posterior thoracolumbar vertebral pedicle screw reduction and fixation combined with vertebral bone implantation via the affected vertebral body under navigational aid for the treatment of thoracolumbar fractures. The efficacy of the procedure was also measured. Between June 2005 and March 2011, posterior thoracolumbar vertebral pedicle screw reduction and fixation plus artificial bone implantation via the affected vertebral pedicle under navigational aid was used to treat 30 patients with thoracolumbar fractures, including 18 males and 12 females, ranging in age from 21 to 57 years. Compared with the values prior to surgery, intraspinal occupation, vertebral height ratio and Cobb angle at the follow-up were significantly improved. At the long-term follow-up, the postoperative Cobb angle loss was <1° and the anterior vertebral body height loss was <2 mm. Posterior thoracolumbar vertebral pedicle screw reduction and fixation combined with vertebral bone implantation via the affected vertebral body under navigational aid may increase the accuracy and safety of surgery, and it is an ideal method of internal implantation. Bone implantation via the affected vertebral body may increase vertebral stability.
spine surgery; thoracolumbar fracture; internal fixation; computer-assisted surgery; bone transplantation
Elevated nitrogen (N) deposition in humid tropical regions may exacerbate phosphorus (P) deficiency in forests on highly weathered soils. However, it is not clear how P availability affects soil microbes and soil carbon (C), or how P processes interact with N deposition in tropical forests. We examined the effects of N and P additions on soil microbes and soil C pools in a N-saturated old-growth tropical forest in southern China to test the hypotheses that (1) N and P addition will have opposing effects on soil microbial biomass and activity, (2) N and P addition will alter the composition of the microbial community, (3) the addition of N and P will have interactive effects on soil microbes and (4) addition-mediated changes in microbial communities would feed back on soil C pools. Phospholipid fatty acid (PLFA) analysis was used to quantify the soil microbial community following four treatments: Control, N addition (15 g N m−2 yr−1), P addition (15 g P m−2 yr−1), and N&P addition (15 g N m−2 yr−1 plus 15 g P m−2 yr−1). These were applied from 2007 to 2011. Whereas additions of P increased soil microbial biomass, additions of N reduced soil microbial biomass. These effects, however, were transient, disappearing over longer periods. Moreover, N additions significantly increased relative abundance of fungal PLFAs and P additions significantly increased relative abundance of arbuscular mycorrhizal (AM) fungi PLFAs. Nitrogen addition had a negative effect on light fraction C, but no effect on heavy fraction C and total soil C. In contrast, P addition significantly decreased both light fraction C and total soil C. However, there were no interactions between N addition and P addition on soil microbes. Our results suggest that these nutrients are not co-limiting, and that P rather than N is limiting in this tropical forest.
Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and “Astrocyte-Cytokine-NMDAR-neuron” pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.