The analgesic effect of transversalis fascia plane block after caesarean section under spinal anaesthesia with intrathecal morphine: a randomised controlled trial.

We aimed to test whether bilateral injection of bupivacaine 0.25% in the transversalis fascia plane reduced 24 h opioid dose after singleton caesarean section, under spinal anaesthesia with intrathecal morphine, compared with saline 0.9% injectate. We allocated randomly 52 women to bilateral injection of 20 ml saline 0.9% on arrival in the post-anaesthesia care unit and 54 women to bilateral injection of 20 ml bupivacaine 0.25% (with adrenaline 2.5 µg.ml-1 ). Mean (SD) cumulative morphine equivalent opioid dose 24 h after saline injection was 32.3 (28.3) mg and 18.7 (20.2) mg after bupivacaine injection, a mean (95%CI) difference of 13.7 (4.1-23.2) mg (p = 0.006). Median (IQR [range]) time to first postoperative opioid dose was 3.0 (1.5-10.3 [0.0-57.4]) h after saline 0.9% and 8.2 (2.7-29.6 [0.2-55.4]) h after bupivacaine 0.25% (p = 0.054). Transversalis fascia plane with bupivacaine 0.25% with adrenaline reduced postoperative pain at rest during 48 h (0-10-point scale) by a mean (95%CI) of 0.9 (0.2-1.6) points (p = 0.013) and on movement by 1.2 (0.4-2.1) points (p = 0.004). We conclude that transversalis fascia plane bupivacaine 0.25% with adrenaline reduces pain and opioid dose after caesarean section compared with saline 0.9%.

Application of principal component analysis with instrumental analysis and sensory evaluation for assessment of chicken breast meat juiciness.

1. The objectives of this study were to use principal component analysis (PCA) to analyse the variability of the three instrumental and 14 descriptive sensory properties of chicken breast meat. The meat was cooked until the internal temperature reached 85°C and further cooked for 0, 20, and 40 min. The second objective was to identify the most critical variables for assessing meat juiciness.2. Cooking loss and moisture content exhibited high correlation with sensorial moisture release and mouth feel.3. The distribution of objects on the axes of the first two principal components (PCs) enabled the identification of three groups undergoing different cooking durations. The four major PCs explained 80.0% of the total variability.4. Cooking loss, moisture content, water-holding capacity, sensorial moisture release and mouth feel were demonstrated as the most effective variables for the first two PCs. PCA with instrumental and sensory analyses proved an effective procedure for systematically and comprehensively judging chicken meat juiciness.

Decreased expression of SorCS1 in colorectal cancer: An independent predictor of poor prognosis.

Previously, we identified that sortilin related VPS10 domain containing receptor 1 (SorCS1) was hypermethylated in colorectal cancer (CRC) tissues. Here, we aimed to investigate the association between CRC and SorCS1. DNA methylation was determined by methylation-specific polymerase chain reaction (MSP) or quantitative real-time methylation analysis (MethyLight). Colorectal cancer tissue specimens from 239 patients that had undergone surgical treatment were evaluated using immunohistochemistry (IHC) analysis for the expression of SorCS1 and correlated with clinicopathological variables and prognosis. We found that SorCS1 was hypermethylated in CRC cell lines and 67.5% (27/40) CRC tumor tissues. The loss of SorCS1 mRNA (p<0.001) and protein expression (p=0.033) were highly correlated with promoter methylation. In addition, SorCS1 expression was significantly increased in younger patients (p=0.006), low CEA level (p<0.001) and pT1-2 stage (p=0.005). Survival analysis revealed that decreased expression of SorCS1 was an independent factor for predicting the increased risk of recurrence (p=0.024) and poor overall survival (p=0.006). Subgroup analysis for CEA level, pT and pN classifications showed that SorCS1 retained its stratified significance only in patients with low CEA level, pT3-4 tumors and pN1-2 lymph node status. Our findings suggest that SorCS1 is epigenetically inactivated in a substantial fraction of CRC, and its expression may be a promising prognostic factor in CRC patients.

Decreased T cell expression of H/ACA box small nucleolar RNA 12 promotes lupus pathogenesis in patients with systemic lupus erythematosus.

Objective To investigate whether the aberrant expression of non-coding RNAs (ncRNAs) in T cells from patients with systemic lupus erythematosus (SLE) could contribute to the pathogenesis of lupus. Methods Expression profiles of RNA transcripts in T cells from three patients with SLE and three controls were analyzed by microarray analysis. Potentially aberrant-expressed ncRNAs were validated using T cell samples from 23 patients with SLE and 17 controls. Transfection studies and microarray analyses were conducted to search for any gene expression that is regulated by specific ncRNAs. Results Initial analysis revealed differential expression of 18 ncRNAs in SLE T cells. After validation, decreased expression of H/ACA box small nucleolar RNA 12 (SNORA12) was confirmed in SLE T cells (0.69-fold, P = 0.007) compared with normal T cells, and its expression level was inversely associated with higher SLE disease activity scores. Jurkat cells transfected with a plasmid encoding SNORA12 showed increased expression of two genes and decreased expression of 15 genes in Jurkat cells. These changes of gene expression were significantly associated with the SLE pathway in the Kyoto Encyclopedia of Genes and Genomes map using microarray analysis. Overexpression of SNORA12 altered the expression of CD69, decreased the expression of histone cluster 1 H4 family member k (HIST1H4K), inhibited the secretion of interferon gamma and the expression of HIST1H4K was increased in SLE T cells. Conclusion Among the ncRNAs, we found that the expression level of SNORA12, which belongs to the family of small nucleolar RNAs, was lower in SLE T cells and affected T cell function. This novel finding suggests that aberrant-expressed snoRNAs lead to dysfunction of T cells and may be involved in the immunopathogenesis of SLE.

Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production.

We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed insulin-like growth factor-1 receptor (IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF-1R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin (IL)-10 production by activated normal T cells, but not RA T cells. The transfection of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines.

Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3(+) anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3(+) anti-CD28(+) lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3(+) anti-CD28(+) LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells.

Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed miRNAs using real-time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant-expressed miRNAs was detected using real-time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR-145, miR-224, miR-513-5p, miR-150, miR-516a-5p, miR-483-5p and miR-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed miR-145 and over-expressed miR-224 were noted. We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with miR-145 suppressed STAT1 and miR-224 transfection suppressed API5 protein expression. Over-expression of miR-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR-145 and miR-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 (STAT)-1 expression in patients with SLE.

Combination of nifedipine and subtherapeutic dose of cyclosporin additively suppresses mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca(2+) -calcineurin-nuclear factor of activated T cells pathway.

Abnormal Ca(2+) -mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca(2+) signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca(2+) level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca(2+) influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca(2+) channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca(2+) -calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA.

Prognostic value of regulator T cells in patients with pancreatic cancer: a systematic review and meta-analysis.

OBJECTIVE: This study focused on investigating the relationship between the level of regulatory T cells (Tregs) infiltration and the prognosis of pancreatic cancer patients by using meta-analysis to identify new clinical diagnostic markers. MATERIALS AND METHODS: We looked through PubMed, Embase, and the Cochrane Library for studies published between the database's inception and September 2021. We included studies that looked at the relationship between Tregs and pancreatic cancer prognosis. We exempted duplicate publications, studies without full text, insufficient information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. The data were analyzed using STATA 15.1. RESULTS: The pooled results show that high infiltrating Treg is highly correlated with lower OS of pancreatic cancer patients (HR=1.56, 95% CI: 1.23-1.990.000), but not with DFS of patients with pancreatic cancer (HR=1.29, 95% CI: 0.88-1.89, p=0.184). On the other hand, the results show that high infiltrating Treg is significantly associated with lower OS (HR=2.13, 95% CI: 1.70-2.67, p=0.000) and DFS (HR=1.79, 95% CI: 1.12-2.86, p=0.015) in patients from Asia, whereas it is not significantly associated with OS and DFS in patients from Europe and America. CONCLUSIONS: This meta-analysis suggests that the assessment of Tregs may help to predict the prognosis in pancreatic cancer patients. Advanced histological techniques for obtaining more detailed information about Treg activity may assist in the identification of novel treatment strategies.

ACTN3 genotype and swimming performance in Taiwan.

Studies have shown that the 577R allele of α-actinin-3 (ACTN3) is more prevalent in sprint athletes than in the general population or in endurance athletes. We examined the distribution of ACTN3 R577X (rs 1815739) genotypes and alleles in the Taiwanese general population (603) and in elite sprint swimmers who had participated in international/national events (168). Additionally, 50 pre-adolescent (age 11-13 years) male students and 38 adult males who completed 12-weeks of swimming training, were included in the present study. We found that the frequencies of the R allele were significantly higher in female international sprint swimmers (67.6%) than in national sprint swimmers (50.0%) or in the general population (53.7%). The 25-m performance was significantly improved across the genotypes after swimming training among the pre-adolescent males but not among the adult males. In addition, pre-adolescents with the RR genotype had the best performance both before and after training although not statistically significant. In conclusion, the frequencies of ACTN3 577R allele were significantly higher in female international sprint swimmers than among national sprint swimmers or the general population. Furthermore, male pre-adolescents with either the ACTN3 RX or XX genotype showed a greater improvement in 25-meter swimming performance than those with the RR genotype.

[Characteristics of CD8+ T cell infiltration in colorectal cancer and their correlation with prognosis].

Objective: As cytotoxic T cells, CD8+ T lymphocytes can kill tumor cells by releasing perforin and other effector molecules, but the correlation between their infiltration level and the prognosis of colorectal cancer varies in previous studies. This study aims to explore the distribution of CD8+T cells in tumor center and invasive margin of colorectal cancer, and to analyze their correlation with the prognosis of patients. Methods: A retrospective cohort study was used to analyze the clinicopathological features of 221 patients with colorectal cancer from the colorectal cancer pathological database of the Sixth Affiliated Hospital of Sun Yat-sen University between 2009 and 2012. Case inclusion criteria: (1) colorectal cancers confirmed by postoperative pathology; (2) patients with follow-up data. Exclusion criteria: (1) multiple primary cancers; (2) inflammatory bowel disease, Lynch syndrome or familial adenomatous polyposis; (3) no available paraffin slides; (4) patients receiving preoperative radiotherapy or chemotherapy. A total of 221 patients met the criteria. Immunohistochemical staining was used to count the CD8+ T cells in tumor center and invasive margin in the paraffin slides. Meanwhile the relative expression of CD8B gene in 22 fresh freeze samples of colorectal cancer was detected. Then the correlation of the expression with CD8+T cell density was examined. The patients were divided into high and low infiltration groups according to the level of CD8+T cells. Log-rank test was applied to compare the overall survival of the two groups of patients, and Cox regression analysis was used to adjust the prognostic significance of CD8+T cell infiltration. Results: There were 118 males and 103 females. In 221 slides, CD8+T cells infiltrating in invasive margin were more than those in tumor center [median (range): 37(0-141) / field vs. 14(0-106) / field, Z=-11.985, P<0.001], and the number of CD8+T cell in the tumor center was positively correlated with those in invasive margin (r=0.610, P<0.001). The number of CD8+ T cell in tumor center was positively correlated with the relative expression of CD8B gene (r=0.524, P=0.012). Survival analysis showed that the overall survival of the high infiltration group was better than that of the low infiltration group both in tumor center and invasive margin (median survival: 84.1 months vs. 73.5 months, P<0.001; 84.2 months vs. 75.9 months, P=0.002). Cox regression analysis revealed that high CD8+T cell infiltration in tumor center was an independent protective factor of overall survival (HR=0.369, 95% CI: 0.168-0.812, P=0.013). Conclusions: The infiltration level of CD8+T cells in tumor center is lower than that in invasive margin, and they are positively correlated. The level of CD8+ T cell infiltration in tumor center is related to overall survival and can be used as a potential pronostic marker.

Effects of PPARγ agonist pioglitazone on cardiac fibrosis in diabetic mice by regulating PTEN/AKT/FAK pathway.

OBJECTIVE: The aim of this study was to explore the role of pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, in cardiac fibrosis of diabetic mice. MATERIALS AND METHODS: A total of 60 adult male C57/B6 mice were divided into 3 groups using a random number table, namely, control group (Sham group, n=20), diabetic cardiomyopathy group (DCM group, n=20), DCM + PIO group (n=20). Streptozocin (STZ) was injected into mice at a dose of 125 mg/Kg to induce the model of diabetes in vivo. After successful induction, mice in DCM + PIO group were intragastrically given PIO at 10 mg/kg/d once a day for 6 weeks. Meanwhile, those in Sham group and DCM group were given the same volume of normal saline. After 6 weeks, ejection fraction % (EF%), fraction shortening % (FS%) and heart rate of mice in each group were examined via echocardiography. Picrosirius red (PSR) staining assay was conducted to detect collagen deposition in myocardial tissues of mice in each group. The protein expression level of PPARγ in mouse myocardial tissues in each group was measured through Western blotting and immunohistochemical staining assays. Hematoxylin-eosin (H&E) staining assay was carried out to evaluate the myocardial hypertrophy of mice in each group. The protein expression level of transforming growth factor-ß (TGF-ß) in mouse myocardial tissues in each group was measured through immunohistochemical staining assay. In addition, Western blotting was employed to detect the expression of proteins related to the phosphate and tension homology deleted on chromsome ten (PTEN)/protein kinase B (AKT)/focal adhesion kinase (FAK) signaling pathway in myocardial tissues of mice in each group. RESULTS: The messenger ribonucleic acid (mRNA) and protein expression levels of PPARγ in mouse myocardial tissues were significantly lower in DCM group than those in Sham group (p<0.05). PPARγ agonist PIO could significantly increase the protein expression of PPARγ in myocardial tissues of DCM mice. The results of cardiac Doppler ultrasound revealed that PIO significantly upregulated EF% and FS% in DCM mice (p<0.05). Besides, PIO remarkably reduced collagen deposition and TGF-ß protein expression in myocardial tissues in DCM mice (p<0.05). H&E staining results showed that PIO notably attenuated myocardial hypertrophy in DCM mice (p<0.05). Furthermore, it was discovered that PIO markedly elevated PTEN protein in myocardial tissues of DCM mice and inhibited the phosphorylation of AKT and FAK proteins (p<0.05). CONCLUSIONS: The protective effect of PIO against cardiac fibrosis in diabetic mice may be related to its regulation on the PTEN/AKT/FAK signaling pathway. Our findings suggest that PIO is expected to become a targeted drug for the treatment of DCM in clinical practice.

Anti-inflammatory effects of pioglitazone on iron-induced oxidative injury in the nigrostriatal dopaminergic system.

AIMS: Transition metals, oxidative stress and neuroinflammation have been proposed as part of a vicious cycle in central nervous system neurodegeneration. Our aim was to study the anti-inflammatory effect of pioglitazone, a peroxisome proliferative activated receptor-γ agonist, on iron-induced oxidative injury in rat brain. METHODS: Intranigral infusion of ferrous citrate (iron) was performed on anaesthetized rats. Pioglitazone (20 mg/kg) was orally administered. Oxidative injury was investigated by measuring lipid peroxidation in the substantia nigra (SN) and dopamine content in the striatum. Western blot assay and DNA fragmentation were employed to study the involvement of α-synuclein aggregation, neuroinflammation as well as activation of endoplasmic reticulum (ER) and mitochondrial pathways in iron-induced apoptosis. RESULTS: Intranigral infusion of iron time-dependently increased α-synuclein aggregation and haem oxygenase-1 levels. Furthermore, apoptosis was demonstrated by TUNEL-positive cells and DNA fragmentation in the iron-infused SN. Systemic pioglitazone was found to potentiate iron-induced elevation in nuclear peroxisome proliferative activated receptor-γ levels. However, pioglitazone inhibited iron-induced α-synuclein aggregation, elevations in interleukin-1ß and interleukin-6 mRNA levels as well as increases in oxygenase-1, cyclo-oxygenase II, nitric oxide synthase and ED-1 protein levels, an indicator of activated microglia. Moreover, iron-induced DNA laddering as well as activation of ER and mitochondrial pathways were attenuated by pioglitazone. In addition, pioglitazone decreased iron-induced elevation in lipid peroxidation in the infused SN and depletion in striatal dopamine level. CONCLUSIONS: Our results suggest that pioglitazone prevents iron-induced apoptosis via both ER and mitochondrial pathways. Furthermore, inhibition of α-synuclein aggregation and neuroinflammation may contribute to the pioglitazone-induced neuroprotection in central nervous system.

Comparison of gadoxetic acid-enhanced MRI and superparamagnetic iron oxide-enhanced MRI for the detection of hepatocellular carcinoma.

AIM: To compare the diagnostic accuracy and sensitivity of gadoxetic acid-enhanced MRI and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Eighty-nine patients (118 HCCs) who underwent three-dimensional gadoxetic acid-enhanced MRI and SPIO-enhanced MRI with a mean interval of 4.7 days (range 3-7 days), were included in this study. Two observers reviewed the gadoxetic acid set (unenhanced, early dynamic, 10 and 20 min hepatocyte-phase images) and SPIO set [unenhanced and ferucarbotran-enhanced T1-, T2-turbo spin-echo (TSE), and T2* weighted imaging (WI)] in consensus. Diagnostic accuracy and sensitivity were evaluated using the alternative-free response receiver operator characteristic (ROC) method. RESULTS: The area under ROC curve (Az value) and sensitivity of the gadoxetic acid set (Az 0.964; sensitivity 90.7%) were significantly higher than those of the SPIO set (Az 0.830; sensitivity 84.7%; p<0.05). There were 14 and seven lesions that were verified only on the gadoxetic acid set and only on the SPIO set, respectively. Four HCCs were clearly revealed as hypointense only on gadoxetic acid-enhanced hepatocyte phase imaging, but were occult on other sequences, including the SPIO set. CONCLUSION: Gadoxetic acid-enhanced MRI is better than SPIO-enhanced MRI for the detection of HCCs.

Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices.

BACKGROUND: Very early rebleeding is frequently encountered in patients with acute oesophageal variceal bleeding. A trial was designed to assess the efficacy and safety in patients with no active bleeding at endoscopy, receiving banding ligation association with terlipressin to prevent very early rebleeding. METHODS: Patients with no active variceal bleeding at endoscopy were evaluated. Eligible patients were randomised to receive terlipressin infusion alone for 5 days (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days (Combined group). Primary endpoints were treatment failure and very early rebleeding. RESULTS: The terlipressin group was composed of 46 patients and the Combined group was composed of 47 patients. Both groups were comparable in terms of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the Terlipressin group and 98% in the Combined group (p = 0.20). Very early rebleeding within 48-120 h occurred in 7 patients (15%) in the Terlipressin group but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002). Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627) was the only predictive factor of very early rebleeding. Blood requirement was significantly lower in the Combined group than in the Terlipressin group. Complications and 6-week survival were similar in both groups. CONCLUSIONS: Combination of banding ligation and terlipressin infusion for 2 days was superior to only infusion of terlipressin for 5 days in the reduction of very early rebleeding and treatment failure in patients with inactive variceal bleeding at endoscopy. TRIAL REGISTRATION NUMBER: ISRCTN28353453.

Early intervention with faecal microbiota transplantation: an effective means to improve growth performance and the intestinal development of suckling piglets.

Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-ß and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.

Ascending aorta replacement vs. total aortic arch replacement in the treatment of acute type A dissection: a meta-analysis.

OBJECTIVE: Acute type A aortic dissection (ATAAD) is a severe, rapidly progressing disease which typically requires patients to undergo emergency surgical intervention. Despite advancements in surgical procedures, still, ATAAD remains a surgical emergency associated with high mortality. The aim of this systematic review and meta-analysis was to compare whether either ascending aorta replacement (AR) or total aortic arch replacement (TR) leads to improved short- and long-term clinical outcomes. MATERIALS AND METHODS: A search of PubMed, Embase, Science Direct, Web of Science, SciELO, BIOSIS, and China National Knowledge Infrastructure (CNKI) databases were supplemented by searching through bibliographies of key articles. Thereafter, data on early and late prognostic factors were extracted. A systematic review and meta-analysis of 15 studies were performed to compare whether either AR or TR leads to a reduction in the risk of in-hospital and short-term mortality, postoperative complications, re-operation rate, and long-term mortality. RESULTS: A total of 15 cohort studies (n = 2822 patients with ATAAD; AR with HA, partial arch = 1911, TR = 911) were deemed eligible and included in the meta-analysis. Compared with TR, AR led to a significantly lower risk of in-hospital mortality (RR = 0.77; 95% CI: 0.61-0.96), shorter cardiopulmonary bypass time (CPB, mean difference = -53.09; 95% CI: -56.68--49.50), circulatory arrest time (CA, mean difference = -8.09; 95% CI: -9.04-7.15), and antegrade cerebral perfusion (ACP, mean difference = -28.62; 95% CI: -30.23--27.00). Differences in the incidence rates of neurological dysfunctions and renal dialysis were not significant. The pooled rate of aortic re-operation was lower in TR group (AR 7.6% vs. TR 5.3%), albeit not significantly (risk ratio = 1.39; 95% CI: 0.94-2.07; p = 0.10). CONCLUSIONS: These findings demonstrate that AR is associated with a lower early mortality rate and shorter operative times overall. Nevertheless, the incidence of postoperative complications in patients undergoing AR is comparable to that of patients undergoing TR. Further prospective follow-up data needs to be collected and analyzed to discern whether there are statistically significant differences in the risks of re-operation and long-term mortality between AR and TR procedures.

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma--a long-term follow-up study.

BACKGROUND: The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear. AIM: To compare the long-term outcome of PAI vs. PEI for treating small HCC. METHODS: From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed. RESULTS: Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group (P = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419-1.975), P = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 +/- 1.0 vs. 2.9 +/- 1.3, P = 0.018). CONCLUSION: Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.

Targeted inhibition of ß-catenin by miR-320 and decreased MMP-13 expression in suppressing chondrocyte collagen degradation.

OBJECTIVE: Wnt/ß-catenin pathway plays a critical role in modulating embryonic development, cell growth, and differentiation. The over-expression of ß-catenin activates this pathway and up-regulates expression of matrix metalloproteinase-13 (MMP-13), and promotes matrix degradation and occurrence of osteoarthritis (OA). This study aims to explore the effect of miR-320 expression in OA chondrocyte and underlying mechanisms. PATIENTS AND METHODS: Chondrocyte tissues from OA patients and normal individuals were collected for the detection of expression levels of miR-320, ß-catenin, MMP-13, and alpha-1 chain of type II collagen (COL2A1). Dual luciferase reporter assay was performed to test targeted regulation between miR-320 and ß-catenin. IL-1ß was used to simulate in vitro cultured chondrocytes, which were transfected with miR-320 mimic and/or si-ß-catenin, followed by quantification of miR-320, ß-catenin, MMP-13, and COL2A1. RESULTS: In chondrocytes of OA patients, expression of microRNA (miR)-320 is decreased. Bioinformatics analysis revealed complementary binding sites between miR-320 and ß-catenin. Compared to control group, increasing levels of ß-catenin and MMP-13 expression with reduction of miR-320 and COL2A1 expressions were observed in OA chondrocytes. Transfection of miR-320 mimic and/or si-ß-catenin depressed expression of ß-catenin and MMP-13 inside chondrocytes, accompanied with elevation of COL2A1 expression. CONCLUSIONS: MiR-320 expression in OA chondrocyte is decreased, accompanied with up regulation of ß-catenin and MMP-13. MiR-320 can inhibit ß-catenin and MMP-13 expressions, elevates COL2A1 expression, which provides novel insights for the treatment of osteoarthritis.

SHP-1 is a negative regulator of epithelial-mesenchymal transition in hepatocellular carcinoma.

This corrects the article DOI: 10.1038/onc.2014.445.