Cholinergic Anti-inflammatory Pathway Attenuates Acute Liver Failure Through Inhibiting MAdCAM1/α4ß7-mediated Gut-derived Proinflammatory Lymphocytes Accumulation.

BACKGROUND & AIMS: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism. METHODS: Co-injection of lipopolysaccharide and D-galactosamine was used to establish the model of ALF. PNU-282987 was used to activate the CAP. Histological staining, real-time polymerase chain reaction, Western blotting, RNA sequencing, and flow cytometry were conducted. Liver biopsy specimens and patients' serum from patients with liver failure were also analyzed. RESULTS: We confirmed that activating the CAP alleviated hepatocyte destruction, accompanied by a significant decrease in hepatocyte apoptosis, pro-inflammatory cytokines, and NLRP3 inflammasome activation. Moreover, hepatic MAdCAM1 and serum MAdCAM1 levels were induced in ALF, and MAdCAM1 levels were positively correlated with the extent of liver damage and the expression of pro-inflammatory markers. Furthermore, activating the CAP mainly downregulated ectopic expression of MAdCAM1 on endothelial cells, and inhibition of NF-κB p65 nuclear translocation was partly attributed to the decreased MAdCAM1. Notably, in ALF, the aberrant hepatic expression of MAdCAM1 subsequently recruited gut-derived α4ß7+ CD4+T cells to the liver, which exhibited an augmented IFN-γ-secreting and IL-17-producing phenotype. Finally, we revealed that the levels of serum and hepatic MAdCAM1 were elevated in patients with liver failure and closely correlated with clinical course. Increasing hepatic infiltration of ß7+ cells were also confirmed in patients. CONCLUSIONS: Activating the CAP attenuated liver injury by inhibiting MAdCAM1/α4ß7 -mediated gut-derived proinflammatory lymphocytes infiltration, which provides a potential therapeutic target for ALF.

Seed protein biotyping in Amaranthus species: a tool for rapid identification of weedy amaranths of concern.

BACKGROUND: The Amaranthus genus contains at least 20 weedy and invasive species, including Amaranthus palmeri (palmer's amaranth) and Amaranthus tuberculatus (tall waterhemp), two species of regulatory concern in North America, impacting production and yield in crops like corn, soybean and cotton. Amaranthus tuberculatus is regulated in Canada with limited establishment, while current climate models predict a range expansion of A. palmeri impacting crop growing areas in Ontario, Quebec and Manitoba. Since many Amaranthus species are similar in their morphology, especially at the seed stage, this demands the development of additional methods that can efficiently aid in the detection and identification of these species. Protein biotyping using Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) has been traditionally used to identify microorganism species, races and pathotypes. Major protein fractions extracted from an organism, ionized and run through a biotyper using mass spectrometry, result in protein spectra that represent a fingerprint at the species or lower taxonomic rank, providing an efficient molecular diagnostics method. Here we use a modified protein biotyping protocol to extract major protein fractions from seeds of the family Brassicaceae to test our protocol, and then implemented the standardized approach in seeds from Amaranthus species. We then created a database of Amaranthus protein spectra that can be used to test blind samples for a quick identification of species of concern. RESULTS: We generated a protein spectra database with 16 Amaranthus species and several accessions per species, spanning target species of regulatory concern and species which are phylogenetically related or easily confused at the seed stage due to phenotypic plasticity. Testing of two Amaranthus blind sample seed sets against this database showed accuracies of 100% and 87%, respectively. CONCLUSIONS: Our method is highly efficient in identifying Amaranthus species of regulatory concern. The mismatches between our protein biotyping approach and phenotypic identification of seeds are due to absence of the species in the database or close phylogenetic relationship between the species. While A. palmeri cannot be distinguished from A. watsonii, there is evidence these two species have the same native range and are closely related.

Transcriptomic analysis of hepatocytes reveals the association between ubiquitin-specific peptidase 1 and yes-associated protein 1 during liver regeneration.

Objectives: The liver has an excellent ability to regenerate, and disrupted liver regeneration after various injuries leads to an unfavorable prognosis for patients. In this study, we sought to identify novel therapeutic hallmarks that are associated with yes-associated protein 1 (YAP1)-mediated hepatocyte proliferation during the process of liver regeneration. Methods: Partial hepatectomy was conducted to induce liver regeneration in rats. Primary hepatocytes were isolated and cultured. Hepatocyte proliferation was assessed using immunohistochemistry staining, and expression of YAP1 was detected. RNA sequencing and bioinformatics analysis were used to search for potential regulators of YAP1. The association between ubiquitin-specific peptidase 1 (USP1) and YAP1 was validated using in vivo and in vitro experiments. Results: YAP1 was significantly elevated in regenerative hepatocytes, especially in the nucleus. Knockdown of YAP1 using small interfering RNA or pharmacological inhibition using verteporfin significantly attenuated the proliferation of hepatocytes. The bioinformatics analysis results revealed that USP1 was associated with YAP1-mediated hepatocyte proliferation during liver regeneration. ML-323, a specific inhibitor of USP1-USP1 associated factor 1 (UAF1), significantly decreased the expression of YAP1, Cyclin D1, and proliferating cell nuclear antigen, while these decreased expressions could be rescued by YAP1 overexpression. Furthermore, ML-323 treatment significantly inhibited liver regeneration following partial hepatectomy. Conclusions: In conclusion, we identified USP1 as a novel biomarker that is associated with YAP1-mediated hepatocyte proliferation in liver regeneration. Pharmacological inhibition of USP1 by ML-323 substantially impairs hepatocyte proliferation during liver regeneration.

Systemic Colonization of Xanthomonas fragariae Strain YL19 Causing Dry Cavity Rot of Strawberry Crown Tissue in China.

Xanthomonas fragariae usually causes angular leaf spot (ALS) of strawberry, a serious bacterial disease in many strawberry-producing regions worldwide. Recently, a new strain of X. fragariae (YL19) was isolated from strawberry in China and has been shown to cause dry cavity rot in strawberry crown. In this study, we constructed a green fluorescent protein (GFP)-labeled Xf YL19 (YL19-GFP) to visualize the infection process and pathogen colonization in strawberries. Foliar inoculation of YL19-GFP resulted in the pathogen migrating from the leaves to the crown, whereas dip inoculation of wounded crowns or roots resulted in the migration of bacteria from the crowns or roots to the leaves. These two invasion types both resulted in the systematic spread of YL19-GFP, but inoculation of a wounded crown was more harmful to the strawberry plant than foliar inoculation. Results increased our understanding of the systemic invasion of X. fragariae, and the resultant crown cavity caused by Xf YL19.

Melatonin ameliorates glyphosate- and hard water-induced renal tubular epithelial cell senescence via PINK1-Parkin-dependent mitophagy.

The combination of glyphosate (Gly) and hard water (Hwt) is a suspected risk factor for chronic interstitial nephritis in agricultural communities (CINAC). Accumulated mitochondrial damage and proximal tubular epithelial (PTE) cell senescence have been implicated in CINAC pathogenesis. Melatonin (Mel) has potential mitochondrial function and renoprotective properties, but its role and mechanism in CINAC are unknown. Here, we detected PTE cell senescence and PTEN-induced putative protein kinase 1 (PINK1)-parkin RBR E3 ubiquitin protein ligase (Parkin)-dependent mitophagy in mice orally administered with different doses of Gly combined with Hwt (Gly: 100 mg/kg·bw and 0.7 mg/L; Hwt: 2,500 mg/L CaCO3 and 250 mg/L Ca2+) for different durations (12 and 36 w) using histological examination, transmission electron microscopy (TEM), immunofluorescence (IF) analysis, and immunohistochemistry (IHC), immunoblotting, ELISA and biochemical assays with kits. The same assays were performed after combination treatment with Mdivi-1 (an inhibitor of mitophagy, i.p. 10 mg/kg·bw, twice a week for 12 w) or Mel (i.p. 10 mg/kg·bw, once a day for 12 w) under high-level exposure. Gly combined with Hwt (Gly-Hwt) significantly increased P16-P21-dependent PTE cell senescence, mitochondrial fission and oxidative stress, and activated PINK1-Parkin-mediated mitophagy, accompanied by defective autophagic flux at high doses but unaltered autophagic flux at low doses. Improved senescence occurred after Mdivi-1 administration, suggesting that mitophagy is involved in cellular senescence. Mel significantly decreased senescence induced by Gly-Hwt. Furthermore, PINK1-Parkin-dependent mitophagy and autophagic flux were markedly enhanced, and mitochondrial function was improved, as evidenced by reductions in mitochondrial fission and subsequent oxidative damage. Thus, Gly and Hwt synergistically promote PTE cell senescence through PINK1-Parkin-mediated mitophagy, and Mel exerts renoprotective effects by modulating mitophagy, suggesting therapeutic applications in ageing-related CINAC.

Exosomes as Potential Functional Nanomaterials for Tissue Engineering.

Exosomes are cell-derived extracellular vesicles of 40-160 nm diameter, which carry numerous biomolecules and transmit information between cells. They are used as functional nanomaterials with great potential in biomedical areas, such as active agents and delivery systems for advanced drug delivery and disease therapy. In recent years, potential applications of exosomes in tissue engineering have attracted significant attention, and some critical progress has been made. This review gives a complete picture of exosomes and their applications in the regeneration of various tissues, such as the central nervous systems, kidney, bone, cartilage, heart, and endodontium. Approaches employed for modifying exosomes to equip them with excellent targeting capacity are summarized. Furthermore, current concerns and future outlook of exosomes in tissue engineering are discussed.

Prognosis of systemic inflammation at an early stage of cirrhosis using the monocyte-to-lymphocyte ratio during malnutrition risk screening: a prospective cohort study.

OBJECTIVE: To determine whether the monocyte-to-lymphocyte ratio (MLR), as a systemic inflammation index, predicts malnutrition risk during the early stages of cirrhosis. METHODS: We conducted a single-center prospective cohort study, enrolling patients from June 2016 to September 2020. The patients underwent malnutrition risk assessments upon admission. The patients were classified into five clinical stages according to portal hypertension. The malnutrition risk was scored using the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) and validated by the Nutritional Risk Screening 2002 (NRS-2002) or Liver Disease Undernutrition Screening Tool (LDUST). Routine clinical laboratory measurements were performed to calculate the MLR, Child-Turcotte-Pugh (CTP) class, and model for end-stage liver disease (MELD) score. The patients were followed up for 2 years. RESULTS: Among the 154 patients with cirrhosis, 60 had compensated cirrhosis and 94 had decompensated cirrhosis. The optimal cutoff value of the MLR, >0.4, was effective in predicting malnutrition related to death or liver transplantation. Those with a high malnutrition risk defined by the NRS-2002 or RFH-NPT had a higher MLR than those with a low malnutrition risk. For patients with class A CTP cirrhosis or a MELD score of <10, an MLR cutoff of <0.4 significantly distinguished more patients with a low malnutrition risk than those with a high malnutrition risk. Both the RFH-NPT score and MLR increased significantly across the decompensated cirrhosis substages. Interestingly, the MLR exhibited a positive correlation with the RFH-NPT score until varices appeared, but the correlation was the highest at the substage of a history of variceal bleeding (r = 0.714, P = 0.009). Multivariable analysis demonstrated that an MLR of >0.4 was an independent factor for malnutrition risk by screening with the RFH-NPT, and this was confirmed using the LDUST and NRS-2002. CONCLUSION: Immune-related inflammatory dysfunction predicts malnutrition risk during the early stages of cirrhosis.

Child Gender and Married Women's Overwork: Evidence from Rural-Urban Migrants in China.

Overwork is one of the risk factors for the work-related burden of disease. In China, nearly a quarter of migrant women are overworked. Working long hours can significantly increase the possibility of migrant women suffering from hypertension and hyperglycemia. The phenomenon of overtime work of migrant women and their health conditions deserves attention. Based on the China Migrants Dynamic Survey in 2016, this study indicates that giving birth to a boy may exacerbate overtime work among migrant women and having more boys in a family increases the probability of women's overwork. Empirical results confirmed the existence of son preferences in China. Compared with women who gave birth to boys, women who gave birth to girls have a lower probability of being a workaholic due to a future fertility plan. Furthermore, the overwork of women is also due to the great economic burden on families to buy a wedding house, brought on by the birth of boys. To overcome the endogenous problem caused by this omitted explanatory variable, this study uses each province's relative sex ratio at birth in 2010 as the instrumental variable of the firstborn's gender. The IV results illustrate that the birth of boys still significantly exacerbates women's overwork. Furthermore, considering age heterogeneity, the influence of son preference on women's overtime work exists throughout their labor life cycle. This paper provides a new perspective for understanding migrant women's overtime work and their health issues in urban China.

Element-Wise Feature Relation Learning Network for Cross-Spectral Image Patch Matching.

Recently, the majority of successful matching approaches are based on convolutional neural networks, which focus on learning the invariant and discriminative features for individual image patches based on image content. However, the image patch matching task is essentially to predict the matching relationship of patch pairs, that is, matching (similar) or non-matching (dissimilar). Therefore, we consider that the feature relation (FR) learning is more important than individual feature learning for image patch matching problem. Motivated by this, we propose an element-wise FR learning network for image patch matching, which transforms the image patch matching task into an image relationship-based pattern classification problem and dramatically improves generalization performances on image matching. Meanwhile, the proposed element-wise learning methods encourage full interaction between feature information and can naturally learn FR. Moreover, we propose to aggregate FR from multilevels, which integrates the multiscale FR for more precise matching. Experimental results demonstrate that our proposal achieves superior performances on cross-spectral image patch matching and single spectral image patch matching, and good generalization on image patch retrieval.

Comparative safety and efficacy of molecular-targeted drugs, immune checkpoint inhibitors, hepatic arterial infusion chemotherapy and their combinations in advanced hepatocellular carcinoma: findings from advances in landmark trials.

Background: Several recent phase 3 trials have reported manageable safety profiles and promising antitumor activities of molecular-targeted drugs (MTDs; sorafenib, lenvatinib), immune checkpoint inhibitors (ICIs; nivolumab, pembrolizumab, atezolizumab), hepatic arterial infusion chemotherapy (HAIC) and their combinations in advanced hepatocellular carcinoma (AHCC); however, head-to-head comparisons among these regimens are lacking. Methods: We aimed to comprehensively review and compare the efficacy and safety of different MTDs, ICIs, HAIC and their combinations in AHCC. Adverse events (AEs), disease control rates (DCRs), objective response rates (ORRs), overall survival (OS) and progression-free survival (PFS) were assessed. Results: The pooled incidence rates of grade 1-5/3-5 AEs were 98.0%/48.6%, 98.3%/57.4%, 91.4%/22.0%, 96.4%/54.6%, 98.2%/61.1%, 86.3%/34.1%, 88.9%/9.4%, and 95.2%/53.2% for sorafenib, lenvatinib, nivolumab, pembrolizumab, atezolizumab plus bevacizumab, HAIC-cisplatin plus sorafenib, HAIC-oxaliplatin, and HAIC-oxaliplatin plus sorafenib, respectively, which suggested that nivolumab exhibited optimal safety regarding grade 1-5 AEs, whereas HAIC-oxaliplatin monotherapy ranked lowest regarding grade 3-5 AEs. According to RECIST1.1, lenvatinib (72.8%), atezolizumab plus bevacizumab (73.6%), HAIC-oxaliplatin (78.8%) and HAIC-oxaliplatin plus sorafenib (75.2%) showed higher DCRs than sorafenib (57.3%), nivolumab (33.9%), and pembrolizumab (62.3%), whereas only HAIC-oxaliplatin-based treatments demonstrated a higher ORR than the others. Pooled OS and PFS analysis favored the combination regimens other than sorafenib along. Conclusions: Here, we present preliminary evidence for the comparative safety and efficacy of existing MTDs, ICIs, HAIC and their combinations in AHCC, which indicated that HAIC-oxaliplatin monotherapy has acceptable toxicity and efficacy and could be the cornerstone for future combination of systemic treatments in AHCC. Our findings might provide insight into the future design of multidisciplinary treatments in AHCC.

Involvement of mitochondrial fission in renal tubular pyroptosis in mice exposed to high and environmental levels of glyphosate combined with hard water.

Chronic interstitial nephritis in agricultural communities (CINAC) has reached epidemic proportions. The combination of glyphosate and hard water has been postulated to play a potent aetiological role in CINAC. Therefore, dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission and subsequent activation of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (Nlrp3)/caspase1 pathway may be involved in the pathogenesis of nephropathy. In the present study, mice were sub-chronically exposed to high doses and environmental levels of glyphosate (100 mg/kg body weight (mg/kg·bw) glyphosate in Roundup and 0.7 mg/L pure glyphosate, respectively) and hard water (2500 mg/L CaCO3 and 250 mg/L Ca2+, respectively) in drinking water. Moreover, Mdivi-1 (Md-1, 10 mg/kg·bw) was intraperitoneally injected to inhibit Drp1 on the basis of the high-dose experiment. Histopathological examination, biochemical analysis, ELISA, western blotting and fluorescent staining were used to analyse renal structure, renal tubular pyroptosis and mitochondrial fission/fusion alterations. The results showed dramatic proximal tubular injury, particularly in the combined groups. Moreover, significant increases in the protein expression levels of calmodulin (CaM), calmodulin-dependent protein kinase II (CaMKII), Drp1/p-Drp1-Ser616 and the Txnip/Nlrp3/caspase1 signalling pathway, and alterations in oxidative stress were observed in the combined groups, and these effects were attenuated by the Drp1 inhibitor Md-1. Intriguingly, there may be a synergistic effect of glyphosate and hard water on renal injury. Taken together, these results suggest that the combination of glyphosate and hard water, even at environmental exposure levels, enhances pyroptosis and ongoing tubulointerstitial inflammation through excessive Drp1-mediated mitochondrial fission.

Renal tubular injury induced by glyphosate combined with hard water: the role of cytosolic phospholipase A2.

BACKGROUND: The combined effects of glyphosate and hard water on chronic kidney disease of unknown etiology (CDKu) have attracted much interest, but the mechanisms remain unknown. Cytoplasmic phospholipase A2 (cPLA2) plays a key role in the acute and chronic inflammatory reactions. This study explored the effect of glyphosate combined with hard water on renal tubules and the possible targets and mechanisms involved. METHODS: In vivo experiments were conducted to investigate the synergistic effects and potential mechanisms of glyphosate and hard water on renal tubular injury in mice. RESULTS: Administration of glyphosate in mice resulted in elevated levels of ß2-microglobulin (ß2-MG), albumin (ALB), and serum creatinine (SCr) compared to control mice. This increase was more pronounce when glyphosate was combined with hard water. In the glyphosate-treated mice, small areas of the kidney revealed fibroblast proliferation and vacuolar degeneration, particularly at the higher dose of 400 mg/kg glyphosate. However, the combination of glyphosate and hard water induced an even greater degree of pathological changes in the kidney. Immunofluorescence and western blot analyses showed that glyphosate and hard water had a coordinated effect on calcium ions (Ca2+)-activated phospholipase A2 and the activation may play a key role in inflammation and renal tubular injury. Exposure to glyphosate alone or glyphosate plus hard water increased the levels of oxidative stress markers and inflammatory biomarkers, namely, thromboxane A2 (TX-A2), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), nitric oxide synthase (NOS), and nitric oxide (NO). Parameters of oxidative stress, including the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were decreased. Further analysis showed that the levels of these biomarkers were significantly different between the mice treated with glyphosate plus hard water and the mice treated with glyphosate alone. CONCLUSIONS: These findings suggested that hard water combined with glyphosate can induce renal tubular injury in mice, and this may involve mitogen-activated protein kinases (MAPK)/cytosolic phospholipase A2 (cPLA2)/arachidonic acid (AA) and its downstream factors.

Royal Free Hospital-Nutritional Prioritizing Tool improves the prediction of malnutrition risk outcomes in liver cirrhosis patients compared with Nutritional Risk Screening 2002.

The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of the RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled co-morbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool (MUST) and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1·5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64·8 and 52·4 %) and specificities (60 and 70 %) than the other tools with regard to screening for malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of the RFH-NPT against the NRS-2002 (63 v. 51 %). The RFH-NPT tended more easily to detect malnutrition risk in patients with advanced Child-Pugh classes (B and C) and lower Model for End-stage Liver Disease scores (<15) compared with NRS-2002. RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using the RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.

Objective and subjective financial status and mortality among older adults in China.

The association between financial status and mortality in older adults is well documented. However, it is unclear whether the association may vary by objective and subjective indicators of financial status. To examine this issue, we used the latest four waves (2005, 2008/2009, 2011/2012, and 2014) of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) of community-residing adults aged 65 and older (n = 25,954). Financial status was assessed using eight objective, subjective, and culturally-oriented measures to capture various dimensions of financial resources at older ages. Multivariate hazard models were used to examine how different indicators of financial status were associated with subsequent mortality in all older adults and by age, gender, and urban-rural residence. Results showed that higher financial status-either objective or subjective-was associated with lower risks of mortality. Subjective assessments of financial status had stronger associations with mortality than objective assessments. The patterns were generally similar between young-old (aged 65-79) and the oldest-old (aged 80+), between women and men, and between rural and urban areas. Together, the findings offer new evidence to help improve the socioeconomic gradient in mortality among older adults in China.

Parecoxib prevents complications in hepatocellular carcinoma patients receiving hepatic transarterial chemoembolization: a prospective score-matched cohort study.

Transarterial chemoembolization(TACE) is the palliative treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). The 242 patients prospectively enrolled in this study were diagnosed with HCC and received TACE at Sun Yat-Sen University Cancer Center between October 2014 and March 2015. Patients were divided into study and control groups based on whether parecoxib sodium was administered postoperatively. Postoperative pain, body temperature, vomiting, changes in liver function, physical activity level, length of hospital stay, and tumor control were evaluated. Compared to the control group after propensity score matching, the study group presented less severe postoperative fever. The daily maximum temperatures in the study and control groups were 37.39 vs. 37.82°C on postoperative day 1 (P < 0.001), 37.10 vs. 37.51°C on day 2 (P < 0.001), and 36.90 vs. 37.41°C on day 3 (P < 0.001). The study group also exhibited greater physical activity (P < 0.05) and had shorter hospital stays (7.21 days vs. 7.92 days, P = 0.041). There were no differences in pain scores. Thus administration of parecoxib sodium to HCC patients after TACE effectively relieved fever, promoted postoperative recovery, and shortened the hospital stay.

Expression of Pim-3 in colorectal cancer and its relationship with prognosis.

There is increasing evidence suggesting that the establishment of Pim-3 is involved in tumorigenesis. This study aimed to investigate the expression and clinicopathological significance of Pim-3 in colorectal cancer (CRC). Clinical pathology data were collected from 410 CRC patients who received radical resection and were pathologically confirmed at the Sun Yat-Sen University Cancer Center between October 2002 and December 2008. We compared the expression Pim-3 in the primary focus and liver metastasis and investigated the correlations with other clinical-pathological factors. Multivariate analysis showed that perioperative blood transfusion, local invasion, lymph node and liver metastasis, and Pim-3 expression were independent prognostic factors. The expression of Pim-3 in CRC was higher than that in normal tissues. Patients with positive expression had significant decreases in 5-year survival. Pim-3 expression showed a positive correlation with tumor cell differentiation, local infiltration, and lymph node and liver metastasis. In conclusion, Pim-3 might serve as a novel target and prognosis factor for colorectal cancer.

Clinicopathologic factors predicting outcomes in patients with gastrointestinal stromal tumors of the rectum and colon.

Limited information is available concerning the clinicopathologic profile of colorectal gastrointestinal stromal tumors (GISTs), which are relatively rare, as well as survival rates following surgical resection. The present study was designed to describe the clinicopathologic characteristics of patients with colorectal GISTs and identify potential factors that may predict postoperative survival outcomes. We reviewed the medical records of 67 patients with colorectal GISTs who underwent surgical resection between January 2000 and December 2012. Clinicopathologic factors affecting overall survival were assessed using the Kaplan-Meier method and multivariate Cox proportional hazards models. The median age at diagnosis was 57 years (range, 32-79 years), with a male-to-female ratio of 1.68. Tumor size varied from 0.2 to 11 cm, with a median size of 5.7 cm. Sixty-two tumors (93%) were positive for CD117, 53 (79%) for CD34, 6 (9%) for PDGFRA, 15 (22%) for SMA, 5 (8%) for S100, and 39 (58%) for vimentin. The overall median survival time was 54 months (95% confidence interval, 32-59 months), and the 1-, 3-, and 5-year overall survival rates were 89.6, 63.9, and 34.4%, respectively. High-risk tumors (determined by histologic grade, size, and other histologic variables) were associated with poor prognosis (hazard ratio, 1.83; 95% confidence interval, 1.21-2.78), and patients who received adjuvant treatment with imatinib had significantly longer median overall survival times than patients who did not (hazard ratio, 0.43; 95% confidence interval, 0.24-0.80). In patients with colorectal GISTs, high-risk tumor histologic grade can predict poor prognosis, and patients may benefit from adjuvant treatment with imatinib. Findings from the present study may provide information to establish evidence-based management strategies for colorectal GISTs.

A multivariate analysis of prognostic determinants for stages II and III colorectal cancer in 141 patients.

BACKGROUND: Previous prognosis analyses of colorectal cancer (CRC) patients with stage II and III disease were done as separate categories. The purpose of this study was to analyze prognostic factors associated with survival in a group of patients who underwent radical resection of stages II and III CRC. METHODS: A retrospective review was performed for 141 consecutive stages II and III patients who had undergone radical resection of colorectal adenocarcinoma between May 2003 and November 2003. Univariate and multivariate analyses were performed to assess the effect of record variables on disease free survival and overall survival. RESULTS: The median follow-up time was 59 months, and the 3- and 5-year survival rates were 76% and 68%, respectively. Four factors were independently associated with a worse disease-free survival: diabetes (hazard ratio (HR) 2.338; 95% confidence interval (CI) 1.011 - 5.407), expression of cyclooxygenase-2 (Cox-2) (HR 0.335; 95%CI 0.126 - 0.888), expression of matrix metalloproteinases 2 (MMP-2) (HR 0.233; 95%CI 0.101 - 0.541), expression of vascular endothelial growth factor (VEGF) (HR 0.295; 95%CI 0.088 - 0.996). Four factors were independently associated with a worse overall survival: lymph nodes metastasis (HR 1.67; 95%CI 1.29 - 2.14), Cox-2 positive (HR 0.056; 95%CI 0.247 - 0.731), MMP-2 positive (HR 0.398; 95%CI 0.190 - 0.836), VEGF (HR 0.364; 95%CI 0.090 - 0.716). CONCLUSIONS: Diabetes, expression of Cox-2, MMP-2 and VEGF were independently associated with a worse disease- free survival. Lymph nodes metastasis, expression of Cox-2, MMP-2 and high level of VEGF predicted a poor overall survival.

Optimal use of adjuvant chemotherapy in stage II colorectal cancer.

BACKGROUND AND OBJECTIVE: The prognosis of stage II colorectal cancer varies. Whether or not to perform adjuvant chemotherapy on patients with stage II colorectal cancer is a controversial issue. The aims of this study were to identify relevant risk factors for the prognosis of stage II colorectal cancer and to evaluate the need for adjuvant chemotherapy. METHOD: Between January 2000 and January 2005, 443 patients with stage II colorectal cancer who had received radical surgery at the Sun Yat-sen University Cancer Center were retrospectively analyzed. The overall survival rates and survival curves were analyzed using the Kaplan-Meier method and log-rank test. Univariate and multivariate prognostic analyses were performed using the Cox regression model. Patients with certain important risk factors were analyzed according to whether they received adjuvant chemotherapy, and four chemotherapeutic regimens were classified into sub-groups and analyzed. RESULTS: Univariate analyses showed that intestinal obstruction or perforation, type 2 diabetes mellitus, an inadequate surgical margin, and sampling of less than 12 lymph nodes were risk factors that correlated with poor prognosis. Patients with an intestinal obstruction or perforation and insufficient lymph node samples achieved higher 5-year survival rates with adjuvant chemotherapy than with surgery alone. CONCLUSION: Intestinal obstruction or perforation, sampling of less than 12 lymph nodes, and inadequate surgical margins were identified as risk factors for poor survival, and patients with either of the first two factors benefited from adjuvant chemotherapy. Moreover, the use of capecitabine alone may be insufficient for patients with an intestinal obstruction or perforation.

[Studies on expectorant compounds in volatile oil from root and rhizome of Aster tataricus].

OBJECTIVE: To research the expectorant components in volatile oil from the root and rhizome of Aster tataricus. METHOD: GC-MS was applied to isolate and identify the compounds. In addition, TLC was used to isolate compound, and its structure was elucidated on the basis of spectral data analysis. At the same time, its expectorant effect was observed by method of the excretion quantity of phenol red in trachea of mice. RESULT: Seven compounds were isolated and identified by GC-MS, they were (R)(-)-p-menth-1-en-4-ol (1), 2-undecanone (2), n-decanoic acid (3), (-)-spathulenol (4), hexahydrofamrnesyl acetone (5), hexadecanoic acid (6), and cis-9, cis-12-octaecadienoic acid (7). A known compound 1-acetoxy-2-ene(E)-4,6- decandiyne was isolated from the root and rhizome of A. tataricus, and it was shown to have expectorant effect. CONCLUSION: 1-Acetoxy-2-ene(E) -4,6- decandiyne, a main compound in volatile oil, had been found to have expectorant effect.