Risk Factors for Severe Complications After Laparoscopic Surgery for T3 or T4 Rectal Cancer for Chinese Patients: Experience from a Single Center.

BACKGROUND Patients with rectal cancer are usually at advanced stage with or beyond serosa invasion in China. Severe complications after laparoscopic rectal surgery leads to prolonged hospitalization and high medical cost. This study aimed to explore risk factors for severe complications after laparoscopic surgery of T3 or T4 rectal cancer. MATERIAL AND METHODS A total of 287 patients diagnosed with T3 or T4 rectal cancer were enrolled from the Department of Gastrointestinal Surgery of Anhui Provincial Hospital from February 2012 to February 2017. Univariate analysis and multivariable logistic regression model were used to analyze the risk factors for severe complications (Clavien-Dindo grade ≥III) after laparoscopic surgery. RESULTS Eighteen patients (6.25%) had severe complications; 15 patients were categorized as Clavien-Dindo grade III, and 3 patients were categorized as Clavien-Dindo grade IV. Univariate analysis showed that male gender, high preoperative white blood cells (WBC), diabetes mellitus, pulmonary dysfunction, and tumor distance from anus were associated with increased risk of severe complications after laparoscopic surgery for rectal cancer. Multivariate analysis showed that preoperative WBC ≥6.9×109/L (OR=5.54 (1.58-19.45), P=0.008), diabetes mellitus (OR=13.07 (3.31-51.67), P=0.000) and pulmonary dysfunction (OR=7.75 (1.69-35.63), P=0.008) were independent risk factors for postoperative severe complications. CONCLUSIONS Preoperative high white blood cells, diabetes mellitus and pulmonary dysfunction were independent risk factors for severe complications after laparoscopic surgery for T3 or T4 rectal cancer.

[Effects of IL-1ß Pretreated Adipose Tissue-derived Mesenchymal Stem Cells on VEGF Secretion and Macrophage M2 Polarization].

OBJECTIVE: To investigate the effects of interleukin (IL)-1ß preteated adipose tissue-derived mesenchymal stem cells (ADMSCs) on vascular endothelial growth factor (VEGF) secretion and macrophages M2 polarization. METHODS: After IL-1ß pretreated ADMSC for 24 h, the expression of cyclooxygenase-2 (COX-2) was detected using Western blot, and the secretions of prostaglandin E2 (PGE2) and VEGF were measured by ELISA method. Conditioned media collected from ADMSCs was used for culturing PMA-U937 macrophages for 72 h, and the expressions of CD163 and IL-10 mRNAs were detected using qRT-PCR. After inhibition of COX-2 expression in ADMSCs by Lentivirus silencing, secretion of VEGF and CD163 and IL-10 mRNA expressions were detected. RESULTS: IL-1ß pretreating ADMSCs increased the expression level of COX-2, enhanced PGE2 and VEGF secretions (P<0.05). In addition, the mRNA levels of CD163 and IL-10 were upregulated when ADMSCs were pretreated by IL-1ß in PMA-U937 cells. After downregulation of COX-2 in ADMSCs, the secretion of VEGF was suppressed, and the mRNA levels of CD163 and IL-10 were also significantly down-regulated. CONCLUSION: IL-1ß pretreatment enhanced the secretion of PGE2 and VEGF, and induced macrophage M2 polarization, which depended on COX-2-PGE2 signal pathway.

Long non-coding RNA BX357664 inhibits gastric cancer progression by sponging miR-183a-3p to regulate the PTEN expression and PI3K/AKT pathway.

Lately, long non-coding RNA (lncRNA) is recognized as a key regulator of gastric cancer (GC) which has aroused great interest in the fields of medicine, toxicology, and functional food. Studies related to LncRNA expression microarray data indicate that BX357664 is down-regulated in GC specimens. However, the expression pattern and molecular mechanism of BX357664 in GC have not been studied so far. The purpose of this study was to investigate the expression of lncRNA BX357664 in GC and its function in GC cell lines. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of BX357664 in 50 pairs of cancer tissues and adjacent non-cancer tissues collected from GC patients. It was found that BX357664 level was lowered in cancer specimens than adjacent non-cancer tissues and correlated with tumor size and TNM stage. Also, we used cell counting kit 8 (CCK8), cell clone formation assay and transwell assay, which affirmed that up-regulation of BX357664 inhibited the proliferation, migration, and invasion of GC cells, but promoted apoptosis. In the dual-luciferase report analysis, BX357664 acted as a miR-183-3p ceRNA to target and regulate the expression of PTEN and affect the PI3K/AKT pathway. These results indicate that BX357664 can inhibit the proliferation and metastasis of GC through the miR-183-3p/PTEN/PI3K/AKT pathway, which may serve as potential targets for the treatment of GC in the future.

Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer.

AIM: To determine whether circular RNAs (circRNAs) are involved in pathological processes of gastric cancer (GC). METHODS: Three circRNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circRNA-miRNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by qRT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC. RESULTS: Hsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues (P < 0.001) and in plasma samples from patients with GC vs healthy controls (P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-node-metastasis stage. The area under the ROC curve (AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen (CEA) level increased the AUC to 0.775. CONCLUSION: Hsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

Depression-like Behavior Induced by Nesfatin-1 in Rats: Involvement of Increased Immune Activation and Imbalance of Synaptic Vesicle Proteins.

Depression is a multicausal disorder and has been associated with metabolism regulation and immuno-inflammatory reaction. The anorectic molecule nesfatin-1 has recently been characterized as a potential mood regulator, but its precise effect on depression and the possible mechanisms remain unknown, especially when given peripherally. In the present study, nesfatin-1 was intraperitoneally injected to the rats and the depression-like behavior and activity of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated. The plasma concentrations of nesfatin-1, interleukin 6 (IL-6), and C-reactive protein (CRP); and the hypothalamic expression levels of nesfatin-1, synapsin I, and synaptotagmin I mRNA were evaluated in nesfatin-1 chronically treated rats. The results showed that both acute and chronic administration of nesfatin-1 increased immobility in the forced swimming test (FST), and resulted in the hyperactivity of HPA axis, as indicated by the increase of plasma corticosterone concentration and hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Moreover, after chronic nesfatin-1 administration, the rats exhibited decreased activity and exploratory behavior in the open field test (OFT) and increased mRNA expression of synapsin I and synaptotagmin I in the hypothalamus. Furthermore, chronic administration of nesfatin-1 elevated plasma concentrations of IL-6 and CRP, which were positively correlated with despair behavior, plasma corticosterone level, and the hypothalamic mRNA expression of synapsin I and synaptotagmin I. These results indicated that exogenous nesfatin-1 could induce the immune-inflammatory activation, which might be a central hug linking the depression-like behavior and the imbalanced mRNA expression of synaptic vesicle proteins in the hypothalamus.

Acute, but not chronic, stress increased the plasma concentration and hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats.

Nesfatin-1, a newly discovered satiety peptide, has recently been reported to be involved in the stress response. Stress-induced expression of nesfatin-1 has been reported and few studies focus on its expression in the hypothalamus, which is the center of the stress response. To test our hypothesis that peripheral and hypothalamic nesfatin-1 overexpression should play an important role in the stress response and the associated hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, acute stress (AS) was induced using water avoidance stress (WAS), and chronic unpredictable mild stress (CUMS) was also induced using 3 consecutive weeks of 7 different stressors. The behavior of CUMS rats was evaluated by an open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). The activity of the HPA axis was detected by measurement of the plasma corticosterone concentration and hypothalamic mRNA expression of corticotropin-releasing-hormone (CRH). The plasma concentration and hypothalamic mRNA expression of nesfatin-1 were measured with an enzyme-linked immunosorbent assay (ELISA) and real-time fluorescent quantitative PCR, respectively. The results showed that both AS and CUMS increased the plasma corticosterone concentration and hypothalamic CRH mRNA expression. Depression-like behavior was induced in CUMS rats, as indicated by a decreased movement distance, frequency of rearing and grooming in the OFT, and sucrose preference index and increased immobility in the FST. Moreover, the AS rats showed increased plasma concentration and hypothalamic mRNA expression of nesfatin-1, which were positively correlated with the plasma corticosterone concentration and hypothalamic CRH expression, respectively. These results indicated that acute stress, but not chronic stress, increased the plasma concentration and hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats.