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This study aims to investigate the relationship between gastrointestinal dysfunction (GD) and cirrhosis severity in cirrhotic patients, to provide evidences for the prevention and treatment of GD in cirrhotic patients. A total of 95 cirrhotic inpatients and outpatients, who were treated in the Department of Gastroenterology of Xinqu Hospital of the First Affiliated Hospital of Henan University of Science and Technology, were enrolled in the present study, and assigned as the experimental group (cirrhosis group). According to Child–Pugh classification, these patients were divided into 3 groups: group A (n = 45), group B (n = 23), and group C (n = 27). Forty healthy adults who received health check-ups during the same period served as the control group. The gastrointestinal (GI) symptoms of cirrhotic patients were scored, and the fasting serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP) levels were measured in all subjects. The potential correlations of GI symptom scores of patients in these cirrhosis groups with GI hormone levels and cirrhosis severity were analyzed. In cirrhotic patients, the GI symptom scores significantly increased. Furthermore, the symptom scores gradually increased along with the aggravation of liver damage. Moreover, serum GAS and VIP levels were significantly higher in the cirrhosis groups than in the control group, whereas MTL levels were significantly lower. These changes were significantly correlated with cirrhosis severity. The linear correlation analysis revealed that the GI symptom score was positively correlated with GAS and VIP levels, and negatively correlated with MTL level. In addition, the linear correlation analysis revealed that GI symptom score and GAS and VIP levels were positively correlated with cirrhosis severity, whereas MTL level was negatively correlated with cirrhosis severity. Cirrhotic patients have more obvious GI symptoms and higher GI hormone levels, which are closely correlated with the progression of liver cirrhosis and the degree of liver function damage.

Purpose The present study examined the correlation of α-dystroglycan (α-DG) expression and like-acetylglucosaminyl transferase (LARGE) with metastasis of human tongue cancer. Materials and Methods Fifty human tongue cancer tissues and 2 tongue squamous cell carcinoma cell lines (CAL27 and SCC4) were involved. Immunohistochemistry was used to detect the expression of α-DG and LARGE. Methylation-specific polymerase chain reaction was performed to assess the methylation status of the LARGE gene promoter. CAL27 and SCC4 cells were transfected with exogenous LARGE and treated with 5-aza-2′-deoxycytidine (Aza-dC), respectively. Glycol sites of α-DG were detected by western blotting. In addition, the laminin overlay assay, cell adhesion assay, and invasion assay were performed. Results Immunohistochemical results showed that decreased expression of VIA4-1 and IIH6 (antibodies that recognize the glycol sites of α-DG) were correlated with the lymph node metastasis of tongue cancer (n = 50; P = .016 and .025, respectively). Decreased LARGE expression and hypermethylation of the LARGE gene promoter were correlated with lymph node metastasis and α-DG glycosylation in human tongue cancer (n = 50; P = .043 and .015 respectively). In addition, LARGE overexpression and Aza-dC treatment actively led to restoration of functional α-DG expression, elevation of laminin binding, and decrease of migratory ability in cancer cells. Conclusion The results suggested that absent α-DG expression and LARGE deregulation were closely associated with nodal metastasis of tongue cancer. Aberrant α-DG expression and glycosylation were attributed at least in part to the abnormal epigenetic modification of LARGE, especially the hypermethylation of its promoter.

To detect the change of nerve growth factor (NGF) level in human amniotic fluid during gestation, and to explore the relationship between this change and fetal ventriculomegaly (VM).The studied subjects (collected from 2004 to 2007) were divided into four groups, including the second-trimester pregnancy group (n=113), third-trimester pregnancy group (n=110), fetal cerebral VM group (n=12), and healthy control group (n=12) which matched with the VM group in gestational weeks. The amniotic fluid specimens were obtained during amniocentesis or cesarean section. The NGF levels in amniotic fluid were detected with enzyme-linked immunosorbent assay.A significantly negative correlation was found between gestational age and the NGF level in amniotic fluid (r=−0.6149, P0.0001). The NGF level in patients with fetal VM was significantly lower than that in healthy controls (33.95plusmn;29.24 pg/mL vs. 64.73plusmn;16.21 pg/mL, P=0.024).NGF levels in amniotic fluid may be a sensitive marker for fetal VM.

Objective To investigate the effect of graded hypothermia on neuropathologic alterations of neonatal rat brain after exposed to hypoxic-ischemic insult at 37°C, 33°C, 31°C, and 28°C, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37°C, 33°C, 31°C, and 28°C, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37°C group, but no death occurred in 33°C, 31°C or 28°C groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37°C (more than 80.0%). The incidence of severe brain damage was significantly decreased in 33°C (53.3%) and 31°C groups (44.4%), and no histologic injury was seen in the 28°C group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37°C group, but minimum in the rat brain of 28°C group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.

To the Editor: I read with great interest the study by Shen et al. titled “Alterations of high endothelial venules in primary and metastatic tumors are correlated with lymph node metastasis of oral and pharyngeal carcinoma and congratulate them on their insightful findings and results”.1 They studied high endothelial venules (HEV) in 64 cases of primary oral and pharyngeal squamous cell carcinoma (OPSCC) and demonstrated morphological and functional changes of HEV during OPSCC progression which were correlated with LN metastasis. They also reported the HEV endothelial cell proliferation rate was the highest in metastatic LNs and concluded these tumor-associated remodeled HEV are correlated with LN metastasis of OPSCC and play a crucial role in the metastasis cascade. This observation, in my opinion, is interesting but not novel. We have previously reported in 2012 very similar findings in 65 cases of tongue SCC and their LN basin.2 In addition, we correlated the HEV immunohistochemistry findings and vessel density with the respective patients’ clinical outcome. We had previously proposed and defined the following HEV parameters as an objective and systematic method of analyzing HEV characteristics.3 Definition of the HEV parameters and ratios (Fig. 1): Figure 1. Definitions of the high endothelial venules (HEV) parameters and its ratios (A) and metamorphosis spectrum of HEV in a nodal microenvironment (B). (A) Venn diagram illustrating the relationship between HEV and their different morphological forms. ... • number of all HEV: A • number of dilated HEV (defined as lumen size more than 80 square micron): B • number of dilated HEV with red blood cells (RBC) within its lumen: C The ratios of these abnormal HEV (B and C) with respect to the total number of HEV (A). • Ratio of dilated HEV to the total number of HEV: B/A • Ratio of dilated HEV with RBC within its lumen to total number of dilated HEV: C/B • Ratio of dilated HEV with RBC within its lumen with respect to total number HEV: C/A We demonstrated the total number of HEV in the LN was found to be significantly associated to disease-free interval and there was a similar association comparing the above defined HEV parameters to overall survival. The density of abnormal HEV was significantly higher in patients with established metastases in their lymph nodes and HEV was shown to be a better prognosis factor than conventional tumor staging.3 This is support of their findings in a few aspects, first the total MECA-79+ vessels (defined by us as “total number of HEV”) was higher in LN with metastasis (P = 0.051) and second HEV-like vessels (defined by us as “abnormal HEV”) was also higher in LN with metastasis (P = 0.037). In their study, they expressed the different morphological forms of HEV as “classic HEVs” and “HEV-like vessels” according to their features. We think the description of “HEV-like vessels” may not be precise as we believe these vessels are in fact originally HEV which have transformed morphologically due to a functional change in the presence of cancer. In my opinion, the term “abnormal or modified HEV” is a more accurate description for these vessels. We also demonstrated similar findings but we believe that the HEV morphological metamorphosis is not in just 2 distinct forms but encompasses a whole morphological spectrum that correlates well with both disease progression and clinical outcome.3 Our hypothesis is that the HEV transformation starts from a normal immunological mediator to a tumor metastasis mediator: this is reflected by morphological changes from a normal appearing HEV, to a dilated HEV, and then to a dilated HEV containing RBC. We believe that this metamorphosis occurs progressively as a spectrum—this process begins with the HEV increasing in absolute numbers, then each becoming more dilated before progressing into a functional vessel carrying blood (Fig. 1B) The authors demonstrated that 12.3% of their cases have HEV-mediated venolymphatic metastases and more than a third (12.3% + 24.7%) of metastasis involves a venolymphatic route. More importantly they have observed that in the cases of HEV-mediated venolymphatic metastases, tumor emboli were situated in the paracortical regions, adjacent to HEVs or just out of the vessels, without any association with lymphatic channels or sinuses. These findings, in addition to the observations that tumor foci were surrounded by abundant HEV, MECA-79+ vessels were observed within the metastatic tumor and that the tumor cells tended to infiltrate to the HEV-rich regions in the front of metastasis, are strongly supportive of our hypothesis that HEV serves as a physical shortcut in the LN for cancer cell metastasis to the systematic vascular system—thereby bypassing the long traditional lymphatic vessel to thoracic duct to subclavian vein route. This is further evident from our observations of the presence of significant abundance of red blood cells within the HEV and significant increase size of its lumen in the presence of a tumor. Our combined findings support the hypothesis that HEV presumably functions like a blood vessel in anticipation to supply the needs for an accelerating growth of a soon-to-arrive tumor deposit, i.e., “preparing the soil”.4,5 As a possible reason for the apparent contradictory findings of high HEV density in primary tumors associated with good prognosis but vice versa when high HEV density are observed in LNs,6 we believe that there is a “point of no return” in this process. HEV proliferate in the primary tumor in response to the cancer, as part of their native and normal immune role, recruiting tumor-associated lymphocytes to combat the tumor and hence, this is reflected and consistent with the findings that high density of HEV and high level of cytotoxic lymphocytes in the primary tumor are often associated with good clinical prognosis.7,8 Once the tumor proliferates beyond the immunotherapy capacity of the tumor-associated T lymphocytes and overwhelms it, tumor cytokines or even single tumor cells escape via lymphatics or tumor HEV themselves to the LN and induces the metamorphosis of the HEV in the LNs from slit-like empty lymphocyte carrier to a large lumen functioning blood vessel. In fact, it was shown that in the presence of cancer, the HEV becomes the predominant blood vessels in the LN.4 Hence, the findings and conclusions of the authors consistently and highly support our previous hypothesis and also provided more evidence that HEV plays a central role in the cancer metastasis cascade. Akin to HEV functioning as a gateway for recruiting lymphocytes in immunological conditions (“lymphocyte trafficking”); in the presence of a cancer, they transformed to that of “tumor cell trafficking” role instead.

This study aims to investigate the gastrointestinal functions of patients with liver failure (LF) based on gastrointestinal dysfunction (GD) scores and serum gastrointestinal hormone levels. The GD in LF patients was scored using the gastrointestinal dysfunction scoring criteria. Serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels were determined in LF patients. In addition, liver function and prothrombin activity were detected, and ultrasonography was performed. The GD score was significantly higher in the LF groups than in the control group. Compared with the control group, serum GAS, CCK, and MTL levels significantly increased in the LF groups, and was positively correlated with the severity of LF. Furthermore, in the LF groups, GD was positively correlated with the severity of LF. However, the GD score and serum GAS, CCK, and MTL levels in the acute LF group were not statistically different, when compared with those in the subacute LF group, acute-on-chronic LF group and chronic LF group. LF plays a key role in the development of GD, and may be the main cause of obvious gastrointestinal symptoms, such as abdominal distension, nausea, vomiting and anorexia, in LF patients. The severity of GD is not associated with LF type, but is positively correlated with the severity of LF, suggesting that GD in LF patients may have complicated mechanisms.

Metastasis is an important cause of cancer-related mortality. In this study, we investigated the role of CCR7 in the lymph node metastasis of tongue carcinoma. Immunohistochemistry and Western blot revealed the expression of CCR7 in tongue SCC tissues and cell lines. In addition, we examined the expression of CCL21, a ligand of CCR7, in normal and diseased lymph nodes using immunohistochemistry and/or real-time PCR. The CCR7 expression was significantly correlated with cervical lymph node metastasis, tumor staging, and histological grade (P = 0.015, 0.040, and 0.015, respectively). The multivariate analysis showed that regional lymph node metastasis, the expression of CCR7, and LVD were the independent poor prognostic factors. Knockdown of CCR7 gene resulted in a significant inhibition of migration and invasion of SCC4 cells in vitro without affecting the proliferation and apoptosis of tumor cells. Also, CCR7 knockdown obviously inhibited cervical lymph node metastasis in an animal tumor model. Our study indicated that CCR7 may play an important role in progression of tongue SCC and could be a promising target for tongue SCC therapy.

Objective: By using colored microsphere (CMS) technique in newborn rats, we explored the relationship between injection sites and blood flow distribution patterns in open-chest and in closed-chest models, with hopes that percutaneous left ventricle injection can be applicable to measure relative blood flow distribution to the brain. Methods: Seven-day-old Wistar rats were used. In open-chest models (n = 30), we exposed the heart and injected CMS (15 mm diameter, 125 000 spheres in 0.05 mL) to left and right ventricles, respectively. In closed-chest models (n = 12), we percutaneously punctured the left ventricle to administer microspheres to see the difference in blood flow distribution between the right and left side of organs. Microsphere counts were compared between the left and right side of each organ by unpaired t-test (mean ± SD). Results: Open-chest showed that right ventricle injection resulted in exclusive entrapment in the lungs, while left ventricle injection resulted in systemic distribution. According to this, one of 12 injections in the closed-chest was judged as right ventricle injection. The other 11 showed insignificant differences between the right and left side in the cortex, lung, and kidney. Conclusion: Right ventricle injection is differentiated from left ventricle injection and microsphere counts are the same between right and left side of the organs, suggesting that percutaneous microsphere injection is applicable for relative blood flow distribution in 7-day-old rat models.