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%.

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.

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.

[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.

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.

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.

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.

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.

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.

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

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

Estimation of Right-Lobe Graft Weight From Computed Tomographic Volumetry for Living Donor Liver Transplantation.

BACKGROUND: The objective of the study was to establish a right-lobe graft weight (GW) estimation formula for living donor liver transplantation (LDLT) from right-lobe graft volume without veins (GVw/o_veins), including portal vein and hepatic vein measured by computed tomographic (CT) volumetry, and to compare its estimation accuracy with those of existing formulas. Right-lobe GW estimation formulas established with the use of graft volume with veins (GVw_veins) sacrifice accuracy because GW measured intra-operatively excludes the weight of blood in the veins. Right-lobe GW estimation formulas have been established with the use of right-lobe GVw/o_veins, but a more accurate formula must be developed. METHODS: The present study developed right-lobe GW estimation formulas based on GVw/o_veins as well as GVw_veins, using 40 cases of Korean donors: GW = 29.1 + 0.943 × GVw/o_veins (adjusted R2 = 0.94) and GW = 74.7 + 0.773 × GVw_veins (adjusted R2 = 0.87). The proposed GW estimation formulas were compared with existing GVw_veins- and GVw/o_veins-based models, using 43 cases additionally obtained from two medical centers for cross-validation. RESULTS: The GVw/o_veins-based formula developed in the present study was most preferred (absolute error = 21.5 ± 16.5 g and percentage of absolute error = 3.0 ± 2.3%). CONCLUSIONS: The GVw/o_veins-based formula is preferred to the GVw_veins-based formula in GW estimation. Accurate CT volumetry and alignment between planned and actual surgical cutting lines are crucial in the establishment of a better GW estimation formula.

TGF-ß upregulates the translation of USP15 via the PI3K/AKT pathway to promote p53 stability.

Crosstalk between transforming growth factor beta (TGF-ß) signaling and p53 has a critical role in cancer progression. TGF-ß signals via Smad and non-Smad pathways. Under normal conditions, wild-type p53 forms a complex with Smad2/3 and co-activates transcription of a variety of tumor suppressor genes, resulting in tumor suppressive effects. Thus, p53 stability is essential in progression of tumor suppressive responses mediated by TGF-ß signaling. However, it remains unknown whether p53 stability is regulated by TGF-ß. In the current study, we identify that USP15 binds to and stabilizes p53 through deubiquitination in U2OS and HEK293 cells. TGF-ß promotes the translation of USP15 through activation of mammalian target of rapamycin by the phosphoinositide 3-kinase/AKT pathway. Upregulation of USP15 translation links the crosstalk between TGF-ß signaling and p53 stability, allowing this cytokine to have a critical role in cancer progression.

Development and Appraisal of Multiple Accounting Record System (Mars).

UNLABELLED: The aim of the system is to achieve simplification of workflow, reduction of recording time, and increase the income for the study hospital. METHODS: The project team decided to develop a multiple accounting record system that generates the account records based on the nursing records automatically, reduces the time and effort for nurses to review the procedure and provide another note of material consumption. Three configuration files were identified to demonstrate the relationship of treatments and reimbursement items. RESULTS: The workflow was simplified. The nurses averagely reduced 10 minutes of daily recording time, and the reimbursement points have been increased by 7.49%. CONCLUSION: The project streamlined the workflow and provides the institute a better way in finical management.

User's Satisfaction of Multiple Accounting Record System.

UNLABELLED: The study hospital had developed a multiple account recording system that generates the accounting information of the consumed materials based on daily nursing records. A questionnaire survey was delivered to further investigate the impact of the system. METHODS: Four concepts of the system were investigated. (1) Supportive and time saving; (2) impact on workflows and job satisfactions; (3) ease of use; and (4) overall satisfactions. RESULTS: The system scored 4.03 out of 5 as the highest for helpfulness for daily practices, 3.98 for decrease the time for recording material consumptions, 3.98 for actually changed the way they work. DISCUSSION: Users mostly expressed positive attitude towards the system.

Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential.

The SET protein is a potent inhibitor of protein phosphatase 2A (PP2A). Here, we report the oncogenic role of SET in hepatocarcinogenesis, clinical aggressiveness and anti-hepatocellular carcinoma (HCC) therapeutics. By analyzing samples obtained from 147 HCC patients, we found that SET overexpression was detected specifically in 30.6% HCC tumor samples, and was significantly associated with worse clinical features and high p-Akt expression in HCC tumors. Co-expression of SET and Akt predicted shorter post-operative recurrence-free survival in this cohort (P=0.045). Furthermore, SET was significantly associated with cell growth and hepatosphere formation. To elucidate the anti-HCC potential of targeting SET, we generated a novel SET antagonist, EMQA (N(4)-(3-ethynylphenyl)-6,7-dimethoxy-N(2)-(4-phenoxyphenyl) quinazoline-2,4-diamine). EMQA enhanced PP2A activity via disrupting SET-PP2Ac (catalytic domain of PP2A) binding in HCC cells, which restored PP2A-mediated p-Akt downregulation and promoted HCC cell death. In HCC cells or recombinant proteins expressing the N- and C- truncated forms of SET, only the C-terminal SET was required for EMQA targeting. Furthermore, combining sorafenib and EMQA showed good synergism in inhibiting HCC survival. Our findings suggested the oncogenic role of SET and the adverse prognostic value of SET overexpression in HCC. This alteration defines a subgroup of HCC patients who could benefit from SET antagonists, such as EMQA.

Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer.

BACKGROUND: Perioperative administration of dexamethasone may augment recurrence and mortality after tumor resection possibly by immunosuppression, which, unfortunately, has never been noted. We therefore carried out a retrospective study in rectal cancer to validate the hypothesis. METHODS: Five hundreds and fifteen patients with stage I to III rectal cancers who underwent a curative resection from June 2007 and June 2011 were enrolled in the current study. Patients who had been given intravenous (IV) dexamethasone (4-10 mg) postoperatively and/or intraoperatively were assigned to dexamethasone group. The outcome of dexamethasone group and non-dexamethasone group were compared. The primary outcome was disease-free survival (DFS) and overall survival (OS). RESULTS: dexamethasone group had significant lower three-year DFS (62.3% vs 71.8%, P = 0.026) and OS (74.1% vs 82.9%, P = 0.031) rate in comparison to non-dexamethasone group, the hazard ratios (HRs) of which were 1.59 (95% CI 1.05-2.39, P = 0.028) and 1.77 (95% CI 1.05-3.01, P = 0.034), respectively. Multivariate analysis revealed that administration of systemic dexamethasone were independently associated with DFS [adjusted HR 1.60 (95% CI 1.03-2.49, p = 0.039)], but for OS, dexamethasone didn't remain significant in this model. In the analyses of a subgroup of 428 patients (55/428 in dexamethasone group) without perioperative blood transfusion, dexamethasone had independently impact on both DFS and OS. CONCLUSION: Patients not given dexamethasone had better three-year survival outcomes compared with patients given dexamethasone perioperatively. Our results indicate that rectal cancer patients treated with curative surgery may get survival benefit from avoiding low-dose perioperative dexamethasone.

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

Epithelial-to-mesenchymal transition (EMT) is well known to involve in tumor invasion and metastasis. Src homology region 2 domain-containing phosphatase 1 (SHP-1) functions as a potent tumor suppressor and also acts as a negative regulator of p-STAT3(Tyr705) oncogenic signaling. However, little is known about the molecular mechanism(s) through which SHP-1 regulates EMT during hepatocellular carcinoma (HCC) progression. Here we first reported that endogenous SHP-1 protein levels were significantly downregulated in cells with mesenchymal characteristics and negatively correlated with p-STAT3(Tyr705) and vimentin but positively correlated with E-cadherin. SHP-1 overexpression abolished transforming growth factor-ß1 (TGF-ß1)-induced p-STAT3(Tyr705) and EMT, as well inhibited migration and invasion but further rescued by signal transducer and activator of transcription factor 3 (STAT3) overexpression. Depletion of SHP-1 could induce a more increase in TGF-ß1-induced p-STAT3(Tyr-705) and EMT characteristics, further supporting the mechanism that suppression of TGF-ß1-induced EMT is dependent on SHP-1-mediated STAT3 inactivation. Constitutively overexpressed SHP-1 tyrosine phosphatase activity by D61A-mutated SHP-1 markedly reduced TGF-ß1-induced p-STAT3(Tyr705) and EMT features but was not altered by C453S catalytic-dead mutant SHP-1. Consequently, SHP-1 acted as a powerful suppressor in preventing EMT by exerting its tyrosine phosphatase activity that directly downregulated p-STAT3(Tyr705). Most notably, we discovered a novel SHP-1 agonist SC-43 better than sorafenib to exert more potent anti-EMT effects in vitro as well as anti-metastatic growth in vivo. In conclusion, SHP-1 is a potent suppressor of HCC EMT and metastasis, thus highlighting that SC-43-SHP-1 axis may serve as a potential therapeutic target that antagonized p-STAT3(Tyr705) and thereby prevented HCC EMT and metastasis.

Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A.

Protein phosphatase 2A (PP2A) is a tumor suppressor, which is functionally defective in various cancers. Previously, we found that PP2A activity determined the anticancer effect of bortezomib and erlotinib in hepatocellular carcinoma (HCC) cells. Here, we tested a novel erlotinib derivative, TD52, in four HCC cell lines, PLC5, Huh-7, Hep3B and Sk-Hep1. Using MTT and flow cytometry, we showed that TD52 had more potent apoptotic effects than erlotinib in HCC cells. TD52-induced apoptosis was associated with dose- and time- dependent reactivation of PP2A and downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A) and p-Akt. Inhibition of PP2A or ectopic expression of CIP2A or Akt in PLC5 cells abolished the effects of TD52. Furthermore, we demonstrated that TD52 affected the binding of Elk-1 to the proximal promoter of the CIP2A gene, thus downregulating transcription of CIP2A. Importantly, TD52-induced tumor inhibition was associated with reactivation of PP2A and downregulation of CIP2A and p-Akt in vivo. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A determines the apoptotic effect induced by TD52. Our findings disclose the therapeutic mechanism of this novel targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans.

BACKGROUND: The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. METHODS: Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. KEY RESULTS: After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p < 0.001) and rapid air injections (p = 0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception (p < 0.001), but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003). CONCLUSIONS & INFERENCES: Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus.