Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.

Sleep-wake behavior is controlled by a wide range of neuronal populations in the mammalian brain. Although the ventral midbrain/pons (VMP) area is suggested to participate in sleep-wake regulation, the neuronal mechanisms have remained unclear. Here, we found that nonspecific cell ablation or selective ablation of GABAergic neurons by expressing diphtheria toxin fragment A in the VMP in male mice induced a large increase in wakefulness that lasted at least 4 weeks. In contrast, selective ablation of dopaminergic neurons in the VMP had little effect on wakefulness. Chemogenetic inhibition of VMP GABAergic neurons also markedly increased wakefulness. The wakepromoting effect of the VMP GABAergic neuron ablation or inhibition was attenuated to varying degrees by the administration of dopamine D1 or D2/3 receptor antagonists and abolished by the administration of both antagonists together. In contrast, chemogenetic activation of VMP GABAergic neurons very strongly increased slow-wave sleep and reduced wakefulness. These findings suggest that VMP GABAergic neurons regulate dopaminergic actions in the sleep-wake behavior of mice.

Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.

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The present study aimed to evaluate the predictive value of pelvic anatomical and clinicopathological parameters for use in the estimation of the likely technical difficulties that may be encountered when performing open rectal surgery for mid-low rectal cancer. Sixty consecutive patients, undergoing open rectal surgery for mid-low rectal cancer were recruited between June 2009 and April 2014. All of the surgical procedures conducted, were low anterior resection (LAR) or abdominoperineal resection (APR). The operations were performed by the same surgeon and surgical team. Pelvic dimensions and angles were measured using three-dimensional reconstruction of spiral computerized tomography (CT) images. Operative time and intraoperative blood loss were used as indicators of operative difficulty. The independent variables were pelvic anatomical and clinicopathological parameters, and the dependent variables were operative time and intraoperative blood loss. Univariate and multivariate analyses were performed in order to determine the predictive significance of these variables. The pelvis width was significantly wider in females than in males (P<0.05), while the sacrococcygeal bending degree was significantly greater in males than in females (P<0.05). No significant difference were detected between the pelvis depth of females and males (P>0.05). Multivariate analyses showed that body mass index (BMI), tumor height, lymph node metastasis, anteroposterior diameter of the pelvic inlet, anteroposterior diameter of the pelvic outlet, height of the pubic symphysis, the sacrococcygeal distance, sacrococcygeal-pubic angle and diameter of the upper pubis to the coccyx were the main factors affecting the operative time (all P<0.05), while the maximum diameter of the tumor was the primary factor affecting intraoperative blood loss (P<0.05). Between the two procedures, the clinicopathological parameters appeared to be more valuable for predicting difficulty in LAR, in which operative time was associated with tumor height and tumor staging (RC2=0.312; P<0.001). By contrast, the pelvic anatomical parameters appeared to be more valuable predictors of variation in APR, in which intraoperative blood loss was associated with the anteroposterior diameter of the mid-pelvis, the anteroposterior diameter of the pelvic outlet, the interspinous diameter, the depth of the sacral curvature and the sacropubic distance (RC2=0.608; P=0.002). BMI, tumor height and the maximum diameter of the tumor may be used to predict the operative difficulty in performing open rectal surgery for mid-low rectal cancer. In addition to the associated clinicopathological parameters, wider, shallower and less curved pelvises may make the greatest contribution to reducing operative time and intraoperative blood loss. Operative difficulty is likely to be increased in deeper and narrower pelvises, or in those with greater sacrococcygeal curvature.

The molecular pathway regulating gastric carcinoma (GC) invasiveness and metastasis remains elusive. Here, we detected significant increase in the phosphorylated epidermal growth factor receptor (pEGFR), MMP7, and MMP13 in the resected GC, compared with the adjacent normal tissue, in patients. Moreover, strong positive correlation was detected between pEGFR and MMP7, and between pEGFR and MMP13 in GC. To examine whether a causal link exists, we used two human GC lines, SNU-5 and AGS, to study the cross talk between EGFR signaling activation, and expression of MMP7 and MMP13. We found that EGF-induced EGFR phosphorylation activated both MMP7 and MMP13, and consequently cancer invasiveness. EGF-induced activation of MMP7 and MMP13 can be both inhibited by use of an inhibitor for EGFR. EGF-induced activation of MMP7 can be also significantly inhibited by use of an inhibitor for Akt, but not an inhibitor for ERK1/2, while EGF-induced activation of MMP13 can be significantly inhibited by use of an inhibitor for ERK1/2, but not by an inhibitor for Akt. These data suggest that EGF-induced activation of MMP7 and MMP13 in GC is through phosphatidylinositol 3-kinase (PI3K) and extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway, respectively. Our study thus highlights EGFR signaling regulated MMP7 and MMP13 activation as molecular basis for metastasis of GC, and further demonstrate that different signaling pathway cascades are involved in the downstream signaling transduction.

Colonic lipomas are rare benign tumors. Colonic intussusception is an uncommon complication of colonic lipoma. The current study presents an unusual case of a 4-cm symptomatic lipoma of the transverse colon causing colonic intussusception. A 65-year-old female was admitted to Wenzhou Central Hospital (Wenzhou, Zhejiang, China) with intermittent pain in the left abdomen that had been present for two weeks. Colonoscopy revealed a 4×5-cm intraluminal spherical mass with erosional mucosa 60 cm above the anal verge, indicating the presence of a malignant gastrointestinal stromal tumor. Contrast-enhanced computed tomography revealed a well-defined fatty tissue mass of 4 cm in diameter in the distal transverse colon proximal to the splenic flexure, with intussusception. The patient underwent segmental resection of the transverse colon and intraoperative frozen sections were obtained. The intraoperative frozen sections revealed a submucosal lipoma of the transverse colon and thus, a conclusive diagnosis was achieved. The patient was followed up for one year and 10 months following the segmental resection of the transverse colon, with a good prognosis. This study may increase clinical awareness with regard to colonic lipomas. Furthermore, open surgery combined with use of intraoperative frozen sections should be recommended for large symptomatic colonic lipomas accompanied by colonic intussusception, thus avoiding unnecessary radical resection and improving patient prognosis.

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