Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

Downregulation of lncRNA EPB41L4A-AS1 promotes gastric cancer cell proliferation, migration and invasion.

BACKGROUND: The incidence of gastric cancer ranks the first among digestive tract tumors in China. However, there are no specific symptoms in the early stage of the tumor and the diagnosis process is complex, so more effective detection methods are very needed. In this study, a novel long noncoding RNA (lncRNA) was introduced as a diagnostic biomarker for gastric cancer, which brought new thinking to the exploration of its pathological mechanism and clinical prediction. METHODS: The level of lncRNA EPB41L4A-AS1 (EPB41L4A-AS1) in gastric cancer serum and cells was verified via real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve was performed based on the EPB41L4A-AS1 level, and the diagnostic possibility of EPB41L4A-AS was analyzed. The chi-square test evaluated the correlation between EPB41L4A-AS expression and clinical information. The cells were cultured and transfected in vitro, and the mediations of abnormal EPB41L4A-AS level on the viability and motility of gastric cancer cells were verified through cell counting kit-8 (CCK-8) and Transwell assay. Furthermore, luciferase activity assay was performed to confirm the sponge molecule microRNA-17-5p (miR-17-5p) of EPB41L4A-AS1. RESULTS: EPB41L4A-AS1 was decreased in gastric cancer, and low EPB41L4A-AS1 level indicated resultful diagnostic value. Overexpression of EPB41L4A-AS1 inhibited the activity of gastric cancer cells, while knockdown of EPB41L4A-AS1 promoted tumor deterioration. EPB41L4A-AS1 directly targeted and regulated the expression ofmiR-17-5p. CONCLUSION: This study elaborated that EPB41L4A-AS1 is lowly expressed in gastric cancer. Silencing EPB41L4A-AS1 was beneficial to cell proliferation, migration, and invasion. EPB41L4A-AS1 provides a new possibility for the diagnosis of gastric cancer patients by targeting miR-17-5p.

SBP1 promotes tumorigenesis of thyroid cancer through TXN/NIS pathway.

BACKGROUND: As the tissue with the highest selenium content in the body, the occurrence and development of thyroid cancer are closely related to selenium and selenoproteins. Selenium-binding protein 1 (SBP1) has been repeatedly implicated in several cancers, but its role and molecular mechanisms in thyroid cancer remains largely undefined. METHODS: The expression of SBP1, sodium/iodide symporter (NIS) and thioredoxin (TXN) were analyzed in clinical samples and cell lines. Cell counting kit-8 (CCK-8) and tube formation assays were used to analyze the cell viability and tube formation of cells. Immunofluorescence was used to determine the expression of the NIS. Co-immunoprecipitation (Co-IP) assay was carried out to verify the interaction of SBP1 with TXN. The mouse xenograft experiment was performed to investigate the growth of thyroid cancer cells with SBP1 knockdown in vivo. RESULTS: SBP1 was significantly increased in human thyroid cancer tissues and cells, especially in anaplastic thyroid cancer. Overexpression of SBP1 promoted FTC-133 cell proliferation, and the culture supernatant of SBP1-overexpression FTC-133 cells promoted tube formation of human retinal microvascular endothelial cells. Knockdown of SBP1, however, inhibited cell proliferation and tube formation. Furthermore, overexpression of SBP1 inhibited cellular differentiation of differentiated thyroid cancer cell line FTC-133, as indicated by decreased expression of thyroid stimulating hormone receptors, thyroglobulin and NIS. Knockdown of SBP1, however, promoted differentiation of BHT101 cells, an anaplastic thyroid cancer cell line. Notably, TXN, a negative regulator of NIS, was found to be significantly upregulated in human thyroid cancer tissues, and it was positively regulated by SBP1. Co-IP assay implied a direct interaction of SBP1 with TXN. Additionally, TXN overexpression reversed the effect of SBP1 knockdown on BHT101 cell viability, tube formation and cell differentiation. An in vivo study found that knockdown of SBP1 promoted the expression of thyroid stimulating hormone receptors, thyroglobulin and NIS, as well as inhibited the growth and progression of thyroid cancer tumors. CONCLUSION: SBP1 promoted tumorigenesis and dedifferentiation of thyroid cancer through positively regulating TXN.

FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/ß-catenin pathway.

Papillary thyroid carcinoma (PTC) is a common malignancy in thyroid tissue. However, the molecular mechanism of PTC tumor progression remains unknown. The hedgehog (Hh) pathway is thought to play a key role during PTC development. Here we investigate the effects of glioma-associated oncogene protein-2 (Gli2), an important transcription factor of the Hh-signaling pathway, on PTC. Gli2 and forkhead box E1 (FOXE1) protein levels were upregulated in tissues of PTC patients and PTC cell lines. Using the PTC cell line TPC-1, we show that Gli2 small interfering RNA (siRNA) reduces cell proliferation, migration, and invasion; whereas overexpression of FOXE1 produces the opposite effects. Moreover, Gli2 siRNA inhibited the expression of genes implicated in the Wnt/ß-catenin pathway and that FOXE1 overexpression produces the opposite effects. Thus, it was indicated that Gli2 promoted the proliferation, migration, and invasion of TPC-1 cells by activating Wnt/ß-catenin and FOXE1 is involved in this process. Xenograft models of PTC were also constructed, the results showed that Gli2 siRNA reduced the rate of tumor growth, FOXE1 levels, and the expression of the Wnt/ß-catenin pathway but FOXE1 overexpression reversed that effects. In conclusion, this study demonstrates that Gli2 promotes the growth of PTC tumors and TPC-1 cell proliferation, migration, and invasion by activating the Wnt/ß-catenin pathway via FOXE1.

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen.

Tenascin-C (TN-C) is an extracellular matrix glycoprotein markedly upregulated during liver fibrosis. The study is performed to explore the role of TN-C during the growth and activation of hepatic stellate cells (HSCs). We found that TN-C was accumulated accompanying with the HSC activation. Our data on cell migration assay revealed that the rTN-C treatment enhanced HSC migration in a dose- and time-dependent manner, but did not influence their proliferation. HSCs transfected with pTARGET-TN-C overexpression vector displayed increased the type I collagen (Col I) production. TN-C overexpression enhanced the process of HSC activation through TGF-ß1 signaling. Moreover, the anti-α9ß1 integrin antibody treatment blocked the TN-C-driven Col I increase in rat HSCs. Collectively, TN-C had a positive role in activation of HSCs mediated by TGF-ß1 and α9ß1 integrin, manifesting elevation of Col I production and promotion of cell migration. Our results provide a potential insight for the therapy of hepatic fibrosis.

[Clinical feature of gallbladder cancer in Northwestern China: a report of 2 379 cases from 17 institutions].

OBJECTIVE: To analyze the clinical features of patients with gallbladder cancer from 17 hospitals in 5 Northwestern provinces (autonomous region) of China from 2009 to 2013. METHODS: A total of 2 379 cases with gallbladder cancer in 17 tertiary hospitals from 5 Northwestern provinces of China from January 2009 to December 2013 were reviewed retrospectively. The clinical data was collected by standardized "Questionnaire for Clinical Survey of Gallbladder Cancer in Northwestern Area of China". χ² test was used to analyze the data. RESULTS: (1) Gallbladder cancer from 17 hospitals accounted for 1.6%-6.8% of all bile tract diseases from 2009 to 2013 in Northwestern China, average was 2.7%. Gallbladder cancer accounted for 0.4%-0.9% of abdominal surgery, average was 0.7%. (2) The incidence of gallbladder cancer was higher in the aged females, the ration of female to male was 1.0 to 2.1. The average age of gallbladder cancer was (64 ± 11) years. The occupation of patients was mainly farmers (χ² = 147.10, P < 0.01). (3) 57.2% of the gallbladder cancers were associated with gallstones. (4) The main pathological patterns of gallbladder cancer were moderate and poor differentiated adenocarcinoma, showing an aggressive malignancy. TNM stage IV accounted for 55.1% of all cases, which was associated with the poor prognosis. (5) The curative resection rate was 30.4%. CONCLUSIONS: Gallbladder cancer is common in the aged females and mainly at advanced stage. The screening and follow-up of high-risk groups with ultrasound and other methods regularly could increase the early diagnosis rate of gallbladder cancer, aggressive surgical resection combined with other comprehensive treatment could improve the prognosis of patients.

MiR-21-mediated Metabolic Alteration of Cancer-associated Fibroblasts and Its Effect on Pancreatic Cancer Cell Behavior: Retraction.

[This retracts the article DOI: 10.7150/ijbs.22555.].

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvß3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM: To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS: SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 µg/kg cerulein plus lipopolysaccharide. mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvß3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS: The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8's beneficial effects in SAP-induced liver injury. CONCLUSION: MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVß3/5.

A modified Hassab's operation for portal hypertension: experience with 562 cases.

BACKGROUND: Many patients with portal hypertension require surgical treatment each year, and Hassab's operation, or esophagogastric devascularization and splenectomy, is an elective procedure. However, it is difficult to devascularize all the vessels of the upper half of the stomach and distal esophagus when hyperblastosis, edema, extensive vein conglobation, and conglutination are present during the operation. These increase the postoperative risk of repeat bleeding. PATIENTS AND METHODS: We modified Hassab's operation to address the difficulties associated with devascularization in these cases. All consecutive Chinese patients with liver cirrhosis and portal hypertension who underwent the modified Hassab operation in the Second Affiliated Hospital of Xi'an Jiaotong University from September 1995 to December 2010 were included in the present retrospective study. RESULTS: A total of 562 modified Hassab's operations were performed, and all the emergency operations performed because of bleeding obtained hemostasis. Although the pressure and blood flow of the portal vein decreased slightly after surgery, it was still maintained at a high level. Overall, 21.8% of the patients had complications, and 4.6% of these patients died during the hospitalization period. Within the 12-month follow-up period, the overall improvement rate of varices was 98.5% and the variceal bleeding rate was 1%. The 5-year bleeding rate was 9.7%. CONCLUSIONS: The modified Hassab operation is an effective procedure for the treatment of portal hypertension. Few early or late complications were observed among the patients.

Machine learning reveals salivary glycopatterns as potential biomarkers for the diagnosis and prognosis of papillary thyroid cancer.

The diagnosis of thyroid cancer, especially papillary thyroid cancer (PTC), is increasing rapidly worldwide. In this study, we aimed to study the glycosylation of salivary proteins associated with PTC and assess the likelihood that salivary glycopatterns may be a potential biomarker of PTC diagnosis. Firstly, 22 benign thyroid nodule (BTN) samples, 27 PTC samples, and 30 healthy volunteers (HV) samples were collected to probe the difference of salivary glycopatterns associated with PTC using lectin microarrays. Then, five machine learning models including K-Nearest Neighbor (KNN), Multilayer Perceptron (MLP), Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM) were established to distinguish HV, BTN and PTC based on the changes of salivary glycopatterns. As a result, SVM had the best diagnostic effect with an accuracy rate of 92 % in testing set. Besides, lectin microarrays were used to explore the differences in salivary glycopatterns of 26 paired salivary samples of PTC patients before and after operation in order to probe into salivary glycopatterns as potential biomarkers for prognosis of PTC patients. The results showed that the levels of salivary glycopatterns recognized by 6 different lectins in patients after the operation almost convergenced with HVs. This study could help to screen and assess patients with PTC and their prognosis based on precise changes of salivary glycopatterns.

Conversion of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition is mediated by oxygen concentration in pancreatic cancer cells.

[This retracts the article DOI: 10.3892/ol.2018.8219.].

Circ_PSD3 promotes the progression of papillary thyroid carcinoma via the miR-637/HEMGN axis.

AIMS: In the present study, we aimed to uncover the potential functions of circular RNA (circRNA) pleckstrin and Sec7 domain containing 3 (circ_PSD3) in papillary thyroid carcinoma (PTC) development. MAIN METHODS: The abundance of circ_PSD3, PSD3 messenger RNA (mRNA), microRNA-637 (miR-637) and hemogen (HEMGN; EDAG-1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was employed to measure cell cycle progression and cell apoptosis. Western blot assay was used to examine protein expression. The proliferation ability and motility of PTC cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays, respectively. The interaction between miR-637 and circ_PSD3 or HEMGN was tested by dual-luciferase reporter assay. Animal experiments were used to explore the role of circ_PSD3 in PTC progression in vivo. KEY FINDINGS: Circ_PSD3 was aberrantly up-regulated in PTC tumor tissues compared with adjacent normal tissues. Circ_PSD3 and HEMGN promoted the cell cycle progression, proliferation and metastasis and impeded the apoptosis of PTC cells. MiR-637 was a direct target of circ_PSD3, and miR-637 directly interacted with HEMGN mRNA in PTC cells. Circ_PSD3 silencing-induced effects in PTC cells were partly attenuated by the addition of anti-miR-637 or HEMGN overexpression plasmid. Circ_PSD3/miR-637/HEMGN regulated the activity of PI3K/Akt signal pathway in PTC cells. Circ_PSD3 silencing inhibited the tumor growth in vivo. SIGNIFICANCE: Circ_PSD3 promoted the progression of PTC through regulating miR-637/HEMGN axis and activating PI3K/Akt signaling. Circ_PSD3/miR-637/HEMGN signaling axis might be a potential target for PTC therapy.

Suppression of long noncoding RNA LINC00324 restricts cell proliferation and invasion of papillary thyroid carcinoma through downregulation of TRIM29 via upregulating microRNA-195-5p.

Long noncoding RNAs (lncRNAs) are identified as novel regulators of carcinogenesis. To date, the precise functions of lncRNAs in papillary thyroid carcinoma (PTC) remains poorly understood. The purposes of this work were to explore the potential relevance of lncRNA 00324 (LINC00324) in PTC. Levels of LINC00324 were markedly up-regulated in PTC. Silencing of LINC00324 significantly repressed the proliferation and invasion of PTC cells. LINC00324 was documented as a sponge of microRNA-195-5p (miR-195-5p). Decreased levels of miR-195-5p were detected in PTC. The up-regulation of miR-195-5p suppressed PTC cellular proliferation and invasion. Suppression of miR-195-5p partially reversed the LINC00324-knockdown-mediated effects in PTC cells. We identified tripartite motif-containing 29 (TRIM29) as a target gene of miR-195-5p. TRIM29 overexpression partially reversed the LINC00324-knockdown- or miR-195-5p-overexpression-mediated effects in PTC cells. In short, this work demonstrates that LINC00324 knockdown inhibits the proliferation and invasion of PTC cells by decreasing TRIM29 expression via up-regulating miR-195-5p expression.

Single nucleotide polymorphisms in telomere length-related genes are associated with hepatocellular carcinoma risk in the Chinese Han population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in telomere-related genes are associated with a high risk of hepatocellular carcinoma (HCC). In this study, we investigated the SNPs of telomere length-related genes and their correlation with HCC risk in the Chinese Han population. MATERIALS AND METHODS: A total of 473 HCC patients and 564 healthy volunteers were recruited. Overall, 42 SNPs distributed in telomere-related genes were selected and identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: We found rs6713088 (OR = 1.27, 95% CI = 1.07-1.52, p = 0.007), rs843711 (OR = 1.29, 95% CI = 1.09-1.54, p = 0.004) and rs843706 (OR = 1.30, 95% CI = 1.09-1.55, p = 0.003) in the ACYP2 gene, rs10936599 (OR = 1.21, 95% CI = 1.02-1.44, p = 0.032) in the TERC gene and rs7708392 (OR = 1.24, 95% CI = 1.00-1.52, p = 0.042) in the TNIP1 gene were associated with high HCC risk (OR > 1). In contrast, rs1682111 (OR = 0.77, 95% CI = 0.64-0.94, p = 0.008) in the ACYP2 gene, rs2320615 (OR = 0.79, 95% CI = 0.64-0.99, p = 0.038) in the NAF1 gene, rs10069690 (OR = 0.75, 95% CI = 0.59-0.96, p = 0.021) and rs2242652 (OR = 0.70, 95% CI = 0.55-0.90, p = 0.004) in the TERT gene were associated with low HCC risk (OR < 1). Based on genotype frequency distributions, rs6713088, rs843645, rs843711 and rs843706 located in the ACYP2 gene as well as rs10936599 in the TERC gene were associated with a high incidence of HCC (p < 0.05). In addition, SNPs in these genes could form a linkage imbalance haplotype. Specifically, the haploid 'GC' formed by rs10069690 and rs2242652 within the TERT gene increased the risk of HCC (p < 0.05). CONCLUSION: SNPs in ACYP2, TERC, TERT and other genes were correlated with HCC risk in the Chinese Han population. These data may provide new insights into early diagnosis and screening of HCC.

M2­TAM subsets altered by lactic acid promote T­cell apoptosis through the PD­L1/PD­1 pathway.

The aim of the study was to investigate the effects of lactic acid on the phenotypic polarization and immune function of macrophages. The human monocyte/macrophage cell line, THP­1, was selected and treated with lactic acid. Immunofluorescence staining, laser confocal microscopy, reverse­transcription polymerase chain reaction (RT­PCR), western blot, siRNA, and ELISA analyses were used to observe changes in the levels of cluster of differentiation (CD)68, CD163, hypoxia inducible factor (HIF)­1α, and programmed death ligand­1 (PD­L1) as well as those of cytokines, tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­12, and IL­10. THP­1 macrophages and T cells were co­cultured in vitro to observe the changes in proliferation and apoptosis of T cells. The results showed that, lactic acid (15 mmol/l) significantly upregulated the expression of the macrophage M2 marker CD163 (P<0.05), cytokines, IFN­Î³ and IL­10, secreted by M2­tumor­associated macrophages (TAM, P<0.05), and HIF­1α and PD­L1 (P<0.05), and downregulated the expression of cytokines, TNF­α and IL­12, secreted by M1­TAM (P<0.05). Redistribution of M2­TAM subsets and PD­L1 expression was reversed after further transfection of THP­1 cells with HIF­1α siRNA (P<0.05). After co­culturing, T­cell proliferation was inhibited and apoptosis was promoted. In summary, modulation of lactic acid level can redistribute M2­TAM subsets and upregulate PD­L1 to assist tumor immune escape. The HIF­1α signaling pathway may participate in this process, revealing that macrophages, as 'checkpoints' in organisms, are links that connect the immune status and tumor evolution, and can be used as a target in tumor treatment.

MicroRNA-4516 suppresses pancreatic cancer development via negatively regulating orthodenticle homeobox 1.

Pancreatic cancer remains one of the most lethal human cancers without efficient therapeutic strategy. MicoRNAs (miRNAs) are a group of small non-coding RNAs involved in multiple biological processes including tumor development and progression. In this study, we investigated the expression and function of miR-4516 in pancreatic cancer. MiR-4516 was low-expressed in pancreatic cancer tissues and cell lines. Overexpression of miR-4516 inhibited pancreatic cancer cell proliferation, migration and invasion, while promoted cell apoptosis in vitro. Further, overexpression of miR-4516 suppressed xenograft pancreatic tumor growth in vivo. Bioinformatics analysis was performed and miR-4516 was predicted to negatively regulate orthodenticle homeobox 1 (OTX1) expression by binding to its 3'-UTR. Consistently, OTX1 was highly expressed in pancreatic cancer tissues and cell lines. Knockdown of OTX1 expression suppressed pancreatic cancer cell migration and invasion, with down-regulated MMP2 and MMP9 expression. Moreover, we demonstrated that miR-4516 regulated pancreatic cancer cell growth, migration, invasion and apoptosis via targeting OTX1. Overexpression of OTX1 could partially abrogate the inhibitory effect of miR-4516. Taken together, we conclude that miR-4516 could function as a tumor suppressor via targeting OTX1. These findings suggest that miR-4516/OTX1 axis might be a novel therapeutic target for miRNA-based therapy for pancreatic cancer patients.

Association of treRNA with lymphatic metastasis and poor prognosis in colorectal cancer.

BACKGROUND: There is an emerging concept that long noncoding RNAs (lncRNAs) are involved in tumorigenesis and could be used as biomarkers. However, the clinical significance of human translational regulatory lncRNA (treRNA) in CRC is largely unknown. The purpose of the study was to examine the value of treRNA as a biomarker in colorectal cancer patients. METHODS: treRNA expression was studied in 78 tumors and adjacent tissues in colorectal cancer patients using quantitative real-time PCR. RESULTS: treRNA was found to be highly expressed in colorectal cancer tissue in contrast to adjacent tissue (P<0.05). Moreover, positive correlation was found between high treRNA expression and lymph node metastasis (P<0.05). Patients with high treRNA expression were found with compromised overall survival (OS) compared with the low treRNA expression group, according to Kaplan-Meier analysis. Moreover, Cox regression model analysis suggested high expression of treRNA as an independent poor prognostic factor for CRC patients. CONCLUSIONS: Overexpression of treRNA could be associated with lymphatic metastasis and compromised survival of CRC. treRNA has potential to be used as a new biomarker for CRC lymphatic metastasis and survival.

Association of family history of tumors with clinicopathological characteristics and prognosis of colorectal cancer.

To investigate the association of family history of malignant tumors with clinicopathological characteristics of colorectal cancer, and its effects on prognosis. We conducted a retrospective review of pathological and follow-up data of patients with colorectal cancer treated in our hospital from January 2010 to December 2015. Of 870 patients undergoing surgery, 737 received follow-up (84.7%). Among them, 192 (26.1%) were family history of malignant neoplasm-positive [MN-FH (+)] and 545 (73.9%) were family history of malignant neoplasm-negative [MN-FH (-)]. MN-FH (+) patients had earlier disease onset, smaller tumor diameter, lower rate of lymph node metastasis, and lower depth of invasion. There were significant differences in BMI between the groups (P<0.05) but no differences in sex or tumor differentiation grade (P>0.05). Rates of Her-2 and p53 protein expression in MN-FH (+) patients were 34.3 and 40.5%, respectively, compared with 22.2 and 26.3% in MN-FH (-) patients. In stage 3, significantly higher Her-2 and p53 protein expression rates were observed in MN-FH (+) than in MN-FH (-) patients. Fluorescence in-situ hybridization showed significantly higher Her-2 expression in MN-FH (+) than in MN-FH (-) patients. The 3 and 5-year overall survival, disease-free survival, and progression-free survival were significantly lower in MN-FH (+) than in MN-FH (-) patients (P<0.05). MN-FH (+) patients with colorectal cancer had earlier disease onset and smaller tumor area, lower invasion depth, a lower rate of lymph node metastasis, and earlier TNM tumor stage at diagnosis than MN-FH (-) patients. BMI value distribution significantly differed between groups. However, long-term prognosis was worse for MN-FH (+) than MN-FH (-) patients, suggesting that internal pathogenic genes play a more crucial role than external environmental factors in prognosis. Family history of tumors could be an independent prognostic factor for colon cancer.

[Effects of alprostadil in prevention of portal vein thrombogenesis after splenectomy and devascularization: a clinical observation of 76 patients with portal hypertension].

OBJECTIVE: To investigate the effects of alprostadil (Lipo PGE1) in prevention of portal vein thrombogenesis (PVT) after splenectomy for portal hypertension. METHODS: Seventy-six patients with portal hypertension undergoing splenectomy and pericardial devascularization were randomly divided into 2 groups :treatment group (n = 40), receiving intravenous drip of injection of radix Salviae miliorrhazae (RSM) 40 ml and alprostadil 20 microg, both once a day since the third day after operation for 2 weeks and then oral administration of dropping pill of SM, and control group (n = 36), receiving intravenous drip of injection of RSM and taking enteric coated aspirin 3 times a day for 2 weeks and then taking dropping pill of SM. Platelets (PLT), prothrombin time (PT), and liver function were detected periodically. Color Doppler ultrasonography was conducted every week to observe the blood flow velocity and diameter of the portal and splenic veins, and if PVT event and ascites occurred. All patients were followed up for 8 - 20 months. RESULTS: No prolongation of coagulation time and bleeding tendency was found in both groups. The PLT number increased remarkably in the 7th to 14th days after operation without significant difference between the 2 groups (P >0.05). The PVT rate of the treatment group was 5.0%, significantly lower than that of the control group (25.0%, chi2 = 6.12, P < 0.05). The ascites rate of the treatment group was 10.0%, significantly lower than that of the control group (33.3%, chi2 = 7.44, P <0.01). The levels of ALT and total bilirubin 7 and 16 days after operation of the treatment group were all significantly lower than those of the control group (all P <0.05). CONCLUSION: Use of alprostadil early after devascularization is an effective and safe measure to prevent PVT, improve liver function, and decrease ascites rate.

MiR-21-mediated Metabolic Alteration of Cancer-associated Fibroblasts and Its Effect on Pancreatic Cancer Cell Behavior.

In this study, we investigated whether the metabolic alteration of cancer-associated fibroblasts (CAFs) occurs via miR-21 remodeling and the effect of this alteration on pancreatic cancer cells. CAFs and normal fibroblasts (NFs) were isolated and cultured. Glucose consumption and lactic acid production were tested, and lactate dehydrogenase (LDHA), pyruvate kinase m2 (PKM2), and miR-21 expression were examined. The level of glycolysis in CAFs was determined after treatment with a miR-21 inhibitor. Primary miR-21-NC CAFs and miR-21-inhibitor CAFs were indirectly co-cultured with BxPc-3 in vitro, and the invasion capacity of these cells was determined. The aerobic oxidation index of cancer cells and the expression of succinodehydrogenase (SDH) and fumarate hydratase (FH) were assessed. Compared with NFs, CAFs showed enhanced glucose uptake capacity, lactic acid production, and elevated LDHA, PKM2, and miR-21 expression. After miR-21 inhibitor treatment, the extent of glycolysis in CAFs was reduced. After indirect co-culture with CAFs, oxidative phosphorylation and SDH, FH, and MCT expression increased in BxPc-3 cells. After co-culture with miR-21-inhibitor-CAFs, oxidative phosphorylation and invasion ability of the pancreatic cancer cells decreased. MiR-21 was involved in metabolic alteration of CAFs and affected the development of cancer cells. This metabolic alteration may be an important mechanism by which the microenvironment promotes tumor progression in a nonvascular manner.