Adenomyosis Accompanied by Multiple Hemorrhagic Cerebral Infarction: A Case Report.

This study aims to present a case of uterine adenomyosis accompanied by multiple hemorrhagic cerebral infarctions (CIs), summarize therapeutic experiences based on the literature review, and improve the clinical diagnosis and treatment of multiple hemorrhagic CIs. This paper describes a 46-year-old female with a four-year history of uterine adenomyosis complicated by multiple hemorrhagic CIs. During treatment, elevated levels of D-dimer, CA-125, and severe anemia were observed. Following internal medicine treatment targeting uterine adenomyosis and hemorrhagic CIs, the cerebral hemorrhage gradually resolved. Women presenting with multiple CIs, particularly hemorrhagic ones, should be evaluated for the presence of gynecological diseases. Treating gynecological conditions may aid in the management of multiple CIs.

Predictive value of cyst/tumor volume ratio of pituitary adenoma for tumor cell proliferation.

BACKGROUND: MRI has been widely used to predict the preoperative proliferative potential of pituitary adenoma (PA). However, the relationship between the cyst/tumor volume ratio (C/T ratio) and the proliferative potential of PA has not been reported. Herein, we determined the predictive value of the C/T ratio of PA for tumor cell proliferation. METHODS: The clinical data of 72 patients with PA and cystic change on MRI were retrospectively analyzed. PA volume, cyst volume, and C/T ratio were calculated. The corresponding intraoperative specimens were collected. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the Ki67 index and nuclear atypia. Patients were categorized according to the Ki67 index (< 3% and ≥ 3%) and nuclear atypia (absence and presence). Univariate and multivariate analyses were used to identify the significant predictors of the Ki67 index and nuclear atypia. The receiver operating characteristic curve assessed the prediction ability of the significant predictors. RESULTS: Larger tumor volumes, smaller cyst volumes, and lower C/T ratios were found in patients with higher Ki67 indexes and those with nuclear atypia (P < 0.05). C/T ratio was an independent predictor of the Ki67 index (odds ratio = 0.010, 95% confidence interval = 0.000-0.462) and nuclear atypia (odds ratio = 0.010, 95% confidence interval = 0.000-0.250). The predictive value of the C/T ratio did not differ significantly from that of tumor volume (P > 0.05) but was better than that of cyst volume (P < 0.05). The area under the curve of the C/T ratio for predicting the Ki67 index and nuclear atypia was larger than that for predicting cyst volume and tumor volume. CONCLUSIONS: C/T ratios can be used to predict PA tumor proliferation preoperatively. Our findings may facilitate the selection of surgery timing and the efficacy evaluation of surgery.

Biomarkers for predicting the severity of spinal cord injury by proteomic analysis.

Purpose: Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for predicting SCI severity. Methods: SCI rat models with mild, moderate, and severe injury were constructed with an electro-mechanic impactor. The behavior assessment and pathological examinations were conducted before and after SCI. Then, quantitative liquid chromatography-mass spectrometry (LC-MS/MS) was performed in spinal cord tissues with different extents of injury. The differentially expressed proteins (DEPs) in SCI relative to controls were identified, followed by Mfuzz clustering, function enrichment analysis, and protein-protein interaction (PPI) network construction. The differential changes of candidate proteins were validated by using a parallel reaction monitoring (PRM) assay. Results: After SCI modeling, the motor function and mechanical pain sensitivity of SCI rats were impaired, dependent on the severity of the injury. A total of 154 DEPs overlapped in the mild, moderate, and severe SCI groups, among which 82 proteins were classified in clusters 1, 2, 3, 5, and 6 with similar expression patterns at different extents of injury. DEPs were closely related to inflammatory response and significantly enriched in the IL-17 signaling pathway. PPI network showed that Fgg (Fibrinogen gamma chain), Fga (Fibrinogen alpha chain), Serpinc1 (Antithrombin-III), and Fgb (Fibrinogen beta chain) in cluster 1 were significant nodes with the largest degrees. The upregulation of the significant nodes in SCI samples was validated by PRM. Conclusion: Fgg, Fga, and Fgb may be the putative biomarkers for assessing the extent of SCI.

Multivisceral resection of nonfunctional pancreatic neuroendocrine neoplasm with nearby organ invasion: a case report.

Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare epithelial malignancies originating from pancreatic neuroendocrine cells, pathologically classified into well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (pNECs). Although they also fall under the category of pNENs, the almost entirely distinct biological characteristics and survival prognosis have caused debate among surgeons when it comes to the development of surgical intervention options, particularly for locally advanced G3 pNETs and pNECs. We present a case of 66-year-old male with nonfunctional G3 pNET, invasion of five nearby pancreatic organs and type II liver metastases. The patient achieved good outcomes after undergoing multivisceral resection and postoperative adjuvant chemotherapy. This finding helps surgeons better understand locally advanced pNENs, formulate treatment decisions systematically and confidently, and balance patient benefits and risks of surgery.

MRI features of pituitary adenoma apoplexy and their relationship with hypoxia, proliferation, and pathology.

OBJECTIVE: We aim to study the MRI features of pituitary adenoma (PA) apoplexy and their relationship with hypoxia, proliferation, and pathology. METHODS: Sixty-seven patients with MRI signs of PA apoplexy were selected. According to the MRI signs, they were divided into the parenchymal group and the cystic group. The parenchymal group had a low signal area on T2WI without cyst >2 mm and this area was not significantly enhanced on the corresponding TW1 enhancement. The cystic group had a cyst >2 mm on T2WI, and the cyst showed liquid stratification on T2WI or high signal on T1WI. The relative T1WI (rT1WI) enhancement value and relative T2WI (rT2WI) value of non-apoplexy areas were measured. Protein levels of hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase 1 (PDK1), and Ki67 were detected with immunohistochemistry and Western blot. Nuclear morphology was observed with HE staining. RESULTS: The rT1WI enhancement average value, rT2WI average value, Ki67 protein expression level, and the number of abnormal nuclear morphology of non-apoplexy lesions in the parenchymal group were significantly lower than those in the cystic group. The protein expression levels of HIF-1α and PDK1 in the parenchymal group were significantly higher than those in the cystic group. HIF-1α protein was positively correlated with PDK1 but negatively correlated with Ki67. CONCLUSION: When there is PA apoplexy, the ischemia and hypoxia of the cystic group are lesser than those of the parenchymal group, but the proliferation is stronger.

Change in the pituitary stalk deviation angle after transsphenoidal surgery can predict the development of diabetes insipidus for pituitary adenomas.

Purpose: We aimed to assess the factors influencing the development of diabetes insipidus after transsphenoidal surgery for pituitary adenomas. Methods: A retrospective analysis was conducted on the clinical data of patients with pituitary adenomas who underwent transsphenoidal surgery. The predictors of postoperative diabetes insipidus were determined using statistical analysis. Results: Of the 415 patients who underwent microscopic transsphenoidal surgery for pituitary adenomas, 196 experienced postoperative diabetes insipidus. The sinking depth of the diaphragma sellae and the difference between the preoperative and postoperative pituitary stalk deviation angles in the diabetes insipidus group were greater than those in the non-diabetes insipidus group. Logistic regression analysis showed that the risk of diabetes insipidus after transsphenoidal surgery was higher in patients with a larger difference in their pituitary stalk deviation angles (odds ratio = 2.407, 95% CI = 1.335-4.342; P = 0.004). Conclusion: The difference in the pituitary stalk deviation angle could predict the onset of diabetes insipidus after transsphenoidal surgery for pituitary adenomas.

Brachyury promotes proliferation and migration of hepatocellular carcinoma via facilitating the transcription of NCAPG2.

Hepatocellular carcinoma (HCC) has a poor prognosis because of its limited drug responses in clinical trials. Therefore, it is crucial to clarify the molecular mechanisms of HCC progression to identify new diagnostic markers and therapeutic targets. Here, we report that brachyury, which regulates the gene encoding the non-SMC condensin II complex subunit G2 (NCAPG2), promotes tumorigenesis in HCC. Knockdown of brachyury led to inhibition of cancer progression in vitro and in vivo. Chromatin immunoprecipitation-sequencing data indicated that the oncogene NCAPG2 is a direct target of brachyury. Furthermore, NCAPG2 knockdown inhibited the proliferation and migration of HCC cells and attenuated brachyury-induced tumorigenesis. Overexpression and decreased DNA methylation of NCAPG2 were associated with a poor prognosis, and NCAPG2 was positively correlated with various immune cell infiltrates, cancer-associated fibroblasts, and immune checkpoint molecule expression levels in the tumor microenvironment. Moreover, the effectiveness of immune checkpoint blockade was decreased in the high NCAPG2 expression group. Together, these findings demonstrated a coregulatory effect of the brachyury/NCAPG2 axis during HCC progression.

Risk factors for delayed postoperative hyponatremia in patients with non-functioning pituitary adenomas undergoing transsphenoidal surgery: A single-institution study.

Purpose: We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery (TSS) in patients with a non-functional pituitary adenoma (NFPA). Methods: We retrospectively collected the clinical data of patients who underwent TSS for NFPA between January 2016 and January 2021. The pituitary region was preoperatively scanned with 3.0 T magnetic resonance imaging. The risk factors for delayed postoperative hyponatremia for NFPA were identified by univariate and multivariable logistic regression analysis. Results: We selected 166 patients with NFPA who fulfilled the inclusion criteria. Delayed postoperative hyponatremia occurred in 28 patients and did not in 138. Multivariable logistic regression analyses demonstrated that higher odds of developing delayed postoperative hyponatremia were independently associated with larger craniocaudal dimension (OR = 1.128, P = 0.034), as well as preoperative hyperprolactinemia (OR = 2.618, P = 0.045) and larger preoperative pituitary stalk deviation angle (OR = 3.033, P = 0.022). Conclusion: We identified the independent risk factors for delayed hyponatremia after TSS for NFPA; these included preoperative hyperprolactinemia, craniocaudal diameter, and preoperative pituitary stalk deviation angle.

Expression of GLUT3 and HIF-1α in Meningiomas of Various Grades Correlated with Peritumoral Brain Edema.

AIM: To investigate the expression of glucose transporter 3 (GLUT3) and hypoxia-inducible factor-1α protein (HIF-1α) in meningiomas and analyze the correlation between GLUT3 and HIF-1α expression with the pathological grade of peritumoral brain edema (PTBE) of meningiomas. METHODS: In this cross-sectional study, we analyzed meningioma specimens from 160 patients collected from January 1, 2014, to December 1, 2017, by dividing them into a low-grade (WHO I) or high-grade (WHO II and WHO III) group. Immunohistochemical analyses were used to detect the expression level of GLUT3 and HIF-1α in the tumor specimens. RESULTS: The proportion of GLUT3-positive staining in tumors sized <4 cm, 4-6 cm, and>6 cm was 35.9% (37/103), 63.6% (28/44), and 53.8% (7/13), respectively (P = 0.007). The proportion of HIF-1α-positive staining in tumors sized <4 cm, 4-6 cm, and >6 cm was 41.7% (43/103), 68.2% (30/44), and 38.5% (5/13), respectively (P = 0.010). The proportion of GLUT3-positive staining in the high-grade group and low-grade group was 70.8% (34/48) and 33.9% (38/112), respectively (P < 0.001). The proportion of HIF-1α-positive staining in the high-grade group and low-grade group was 62.5% (30/48) and 42.9% (48/112), respectively (P = 0.023). GLUT3-positive expression in meningioma PTBE grades 0, I, II, and III was 20.3% (13/64), 41.2% (14/34), 63.6% (21/33), and 82.8% (24/29), respectively (Bonferroni-corrected, P < 0.001, α/6 = 0.008). HIF-1α-positive expression in meningioma PTBE grades 0, I, II, and III was 34.4% (22/64), 47.1% (16/34), 54.5% (18/33), and 75.9% (22/29), respectively (Bonferroni-corrected, P = 0.003, α/6 = 0.008). Spearman's correlation analysis revealed a correlation between the expression of GLUT3 and HIF-1α in meningiomas (r = 0.463, P < 0.001). Multivariate analysis revealed that GLUT3-positive expression, HIF-1α-positive expression, and high pathological grade were associated with the development of PTBE (P < 0.05). CONCLUSIONS: GLUT3 and HIF-1α expression in meningiomas was closely related to the tumor size, pathological grade, and PTBE. This study is the first to report a unique map-like multifocal GLUT3 staining pattern in meningiomas.

Modafinil ameliorated pancreatic injury and inflammation through upregulating SNIP1.

Acute pancreatitis (AP) is the inflammatory response of the exocrine pancreas to various causes. Modafinil has significant anti-inflammation and anti-oxidation effects. No experiment has assessed the effects of modafinil on AP. Thus, the study aims to study the effects of modafinil on AP and its potential mechanism in vivo and vitro. 5% sodium taurocholate was retrograde injected into pancreatic duct to establish AP rat model. The severity of AP was detected by HE staining, serum amylase and lipase levels. The inflammation, oxidative stress and apoptosis were detected separately by ELISA, MDA and SOD kits, tunnel staining and Western blotting in rats. Besides, SNIP1 expression was analyzed by qPCR and Western blotting. In vivo, AR42J cells were stimulated by cerulein and lipopolysaccharide to establish AP cell model. Flow cytometry examined cell apoptosis. After the plasmids silencing SNIP1 were transfected into AP cells, the inhibitory effects of modafinil on inflammation, oxidative stress and apoptosis were significantly reversed. The results indicated that modafinil showed significant curative and therapeutic effects by regulating SNIP1 level.

Sinensetin flavone exhibits potent anticancer activity against drug-resistant human gallbladder adenocarcinoma cells by targeting PTEN/PI3K/AKT signalling pathway, induces cellular apoptosis and inhibits cell migration and invasion.

PURPOSE: The main focus of the current research work was to unveil the anticancer activity of the naturally occurring Sinensetin flavone against aggressive gall bladder cancer adenocarcinoma (GBAC) TJ-GBC2 cell line. Its effect of inducing apoptosis mediated via targeting PTEN/PI3K/AKT signalling pathway were also examined along with cell migration and invasion. METHODS: Cell proliferation was tested by MTT cell viability assay. Fluorescence microscopy was utilized to carry out apoptosis related studies via DAPI staining along with flow cytometry using annexin V/propidium iodide (PI) assay. Further, western blotting analysis was carried out to examine the effects of Sinensetin on the expressions of apoptosis-related proteins and Bax Bcl-2 along with PTEN/PI3K/AKT signalling pathway. The impact of the test molecule on cell migration and invasion was studied through wound healing assay and transwell cell invasion assay respectively. RESULTS: The results showed that Sinensetin treatment caused a significant retardation in cell viability, in a dose-dependent fashion. DAPI staining assay and annexin V/PI assay revealed that the cell viability of GBC cells was retarded due to induction of apoptosis. It was also associated with downregulation of Bcl-2 and upregulation of Bax levels. Further, wound healing assay and transwell cell invasion assay revealed that cell migration as well as cell invasion of cancer gallbladder cells was decreased in a concentration-dependent fashion. It was further seen that Sinensetin treatment resulted in inhibition of matrix metalloproteinase (MMP)-2 and enhancement of MMP-9 protein expressions. Results also showed that the tested molecule had the potential to inhibit PTEN/PI3K/AKT signalling pathway. CONCLUSION: In conclusion, the current study indicated that Sinensetin flavone has the potential to be developed as a candidate drug against gallbladder adenocarcinoma provided more toxicological and in vivo studies are carried out.

Application of the Three Points and Three Lines Method to Accurately Open the Sellar Floor in Microscopic Transsphenoidal Surgery of Pituitary Adenomas.

OBJECTIVE: In this study, the sellar floor morphology of patients with pituitary adenoma is analyzed and a simple yet reliable method is identified to determine the location of bone window opening. METHODS: Clinical information of 144 consecutively admitted patients was retrospectively analyzed. Enhanced magnetic resonance imaging of the midsagittal plane was selected as the reference for classifying the sellar floor. Intraoperative tumor location, extent of tumor resection, and follow-up results were analyzed for different types of sellar floor. The tuberculum sellae, lowest point of the sphenoid sinus, and the lowest point of the sellar floor and 3 lines related to them were used to classify the sellar floor. This is referred to as the "three points and three lines" method. RESULTS: Based on its location in the sphenoid sinus, the sellar floor can be classified into 4 types: 12 patients (8.3%) with high sellar, 70 (48.6%) with medium sellar, 30 (20.8%) with low sellar, and 32 (22.8%) with steep sellar. The maximum tumor diameter, maximum sellar floor diameter, and the intercarotid distance were all significantly different among patients with different types of sellar floor (P < 0.001). For all patients, quick intraoperative location of the sellar floor opening was achieved. A total of 104 patients (72.2%) had total tumor resection, 28 (19.40%) had subtotal tumor resection, and 4 (2.8%) had partial tumor resection. Twenty patients (13.9%) experienced cerebrospinal fluid leak, and there was no significant difference in cerebrospinal fluid leak rate among groups. CONCLUSIONS: Presurgical classification and location of the sellar floor are critical for understanding and assessing the transsphenoidal approach. Different types of sellar floor appeared in the surgery with different morphologic features. The three points and three lines method helps the surgeon to predetermine the location of the sellar floor opening and to shorten surgical time.

Axin1 inhibits proliferation, invasion, migration and EMT of hepatocellular carcinoma by targeting miR-650.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate and low survival rate. This study was designed to explore a novel molecular with high sensitivity and specificity, which can be applied in early diagnosis and therapeutic evaluation of HCC. The current study aims to investigate the effect and important role of Axin1 on cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. qRT-PCR results showed lower Axin1 expression level and higher miR-650 expression level in HCC. Luciferase reporter assay was carried out to verify the negative correlation between Axin1 and miR-650 mRNA levels. CCK-8 assay results showed that the cell proliferation ability was significantly suppressed by Axin1 overexpression in SK-HEP-1 cells. The results in wound healing assay uncovered that cell migration ability was markedly suppressed by Axin1 overexpression. The results in trans-well invasion assay showed that Axin1 overexpression caused decreased invasive ability in SK-HEP-1 cells. The WB results showed that the protein level of E-cad was significantly increased and the protein levels of N-cad, vimentin and snail were obviously reduced following Axin1 overexpression. Whereas, the suppressive effects on cell proliferation, migration, invasion and EMT caused by Axin1 overexpression were abolished by miR-650 mimic. All the results in the current study confirmed the truth that Axin1 overexpression could suppress cell proliferation, migration, invasion and EMT by downregulating miR-650 expression.

Role of miR-18a and miR-25 disruption and its mechanistic pattern in progression of liver cancer.

This study examined the molecular mechanisms underlying the roles of the microRNAs miR-18a and miR-25 in the progression of human liver cancer. Liver cancer biopsies obtained from early-stage liver cancer patients were examined by qRT-PCR and Northern blotting to examine the expression of miR-18a and miR-25. Both microRNAs were overexpressed in mouse primary hepatocytes following transfection of the cells with vectors encoding the microRNAs. An analysis of biopsy samples from liver cancer patients indicated that both miR-18a and miR-25 were overexpressed during the early stages of liver cancer. Further, qRT-PCR and Northern blotting confirmed that both of these microRNAs play crucial roles in the progression of liver cancer. Our findings clearly indicate that miR-18a and miR-25 can be used as prognostic biomarkers for early-stage liver cancer. Hence, miR-18a and miR-25 may have value as prognostic indicators and may facilitate the development of novel therapeutics for liver cancer.

miR-1470 regulates cell proliferation and apoptosis by targeting ALX4 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. MicroRNAs (miRNAs) have been proven to play essential roles in different cancers, including HCC. The current study was mainly focused on the role of miR-1470 in HCC progression. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression levels of miR-1470 and Aristaless-like homeobox-4 (ALX4). The CCK-8 and EdU assays were used to examine cell proliferation. Flow cytometric analysis was used to elucidate the cell cycle and cell apoptosis. A xenograft tumor assay was carried out to verify the effect of miR-1470 on tumor formation in vivo. RESULTS: According to the qRT-PCR assay, miR-1470 was proven to be overexpressed in HCC. As shown by the CCK-8 assay, EdU assay and flow cytometric analysis, miR-1470 overexpression promoted cell proliferation and inhibited cell apoptosis. ALX4 was proven via a dual luciferase reporter assay to be a downstream target gene of miR-1470. ALX4 was downregulated in HCC. The results of a rescue assay revealed that miR-1470 had an oncogenic role in HCC by regulating ALX4. CONCLUSION: miR-1470 exhibits an oncogenic role in HCC by targeting ALX4. The data from our study may provide novel insight for the identification of new biomarkers and treatment strategies for HCC.

Comparison on the Efficacy of Three Duct Closure Methods after Laparoscopic Common Bile Duct Exploration for Choledocholithiasis.

BACKGROUND Laparoscopic common bile duct exploration (LCBDE) is currently the best approach for complex cases of choledocholithiasis or the cases of endoscopic retrograde cholangiopancreatography (ERCP) failure. Nevertheless, there is no clear consensus on the optimal duct closure method after LCBDE. The purpose of this study was to evaluate the efficacy of 3 duct closure methods after LCBDE for choledocholithiasis. MATERIAL AND METHODS In this analysis, 189 patients with choledocholithiasis underwent LCBDE between June 2014 and December 2018. According to different duct closure methods, these patients were divided into T-tube drainage (TTD) group (n=66), common suture group (n=64) and barbed suture group (n=59). The operation time, suturing time, amount of intraoperative bleeding, tube-carried time, length of stay (LOS), hospitalization costs, pre- and post-operative common bile duct (CBD) diameters were all compared among the 3 groups. Six months after discharge, the incidence of complications and recurrent stones was observed. RESULTS The operation time, suturing time, and amount of intraoperative bleeding in barbed suture group were both significantly less than those in the common suture group and the TTD group (P<0.01). When compared with the TTD group, the suturing time, tube-carried time, and LOS were decreased markedly in the common suture group and the barbed suture group (P<0.01). The post-operative CBD diameters in the 3 groups were all significantly larger than the pre-operative CBD diameters (P<0.01). There was no statistical significance among the 3 groups regarding the incidence of complications and recurrent stones (P>0.05). CONCLUSIONS Barbed suture shortened the suturing time, operation time, tube-carried time, and LOS, and lessened the amount of intraoperative bleeding in patients with choledocholithiasis after LCBDE. It was more effective than the common suture and TTD.

A novel mutation in INS gene linked to permanent neonatal diabetes mellitus.

PURPOSE: Neonatal diabetes mellitus (NDM) is caused by mutations in the genes responsible for pancreatic ß cell mass or function. This study aimed to screen the mutations in the KCNJ11, ABCC8, and INS genes in a Chinese patient with clinical features of NDM. METHODS: The entire coding sequence and exon/intron boundaries of KCNJ11, ABCC8, and INS genes were detected by Sanger sequencing. The pathogenicity of the mutation was determined by using online prediction programs SIFT and Mutation Taser. The conformational alterations which contribute to the change of protein function were analyzed at the structural level. RESULTS: A novel mutation L35Q (B11) of the INS gene was discovered in the patient. As L35 residue contributes to its hydrophobic core of the protein, the L35Q substitution is predicated to affect B19-A20 disulfide bond and therefore disrupt the folding of the proinsulin, which ultimately results in beta cell apoptosis by inducing ER stress. CONCLUSIONS: This case could help us understand the role of the INS mutation in the development of diabetes.

MNX1 promotes cell proliferation and activates Wnt/ß-catenin signaling in colorectal cancer.

Aberrant Wnt/ß-catenin signaling is a characteristic feature of colorectal cancer (CRC), therefore, understanding the underlying mechanisms of aberrant Wnt/ß-catenin signaling will improve the treatment outcome of CRC. Expression of MNX1 in paired fresh CRC tissues and corresponding adjacent normal tissues were examined by qPCR and Western blotting. The levels of MNX1 in paraffin-embedded CRC specimens were detected by immunohistochemistry (IHC). The role of MNX1 in growth and proliferation of CRC cells was evaluated by MTT and colony formation assay. Luciferase reporter analysis and western blotting were carried out to explore the influence of MNX1 on Wnt/ß-catenin signaling. The results showed that expression of MNX1 is markedly upregulated in CRC tissues and positively correlated with level of Ki67, and overexpression of MNX1 significantly promotes the proliferation of CRC cells. Further study showed that ectopic expression of MNX1 activates the Wnt/ß-catenin signaling and upregulates the expression of c-Myc and CCND1, the downstream genes of Wnt/ß-catenin signaling. Therefore, MNX1 plays an indispensable role in promoting of human CRC progression and may represent a novel therapeutic target for CRC.

GLUT3 expression in cystic change induced by hypoxia in pituitary adenomas.

Tumor cells require large amounts of energy to sustain growth. Through the mediated transport of glucose transporters, the uptake and utilization of glucose by tumor cells are significantly enhanced in the hypoxic microenvironment. Pituitary adenomas are benign tumors with high-energy metabolisms. We aimed to investigate the role of expression of glucose transporter 3 (GLUT3) and glucose transporter 1 (GLUT1) in pituitary adenomas, including effects on size, cystic change and hormone type. Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7 (5/22), 50.4 (66/131) and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P = 0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, we found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, our results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas.