Value of the Prognostic Nutritional Index in Surgery for Crohn Disease in China and the Effects on Outcome: A Retrospective Study.

PURPOSE: To investigate the value of the Prognostic Nutritional Index (PNI) in the surgery of Crohn Disease and examine the ability of PNI to predict poor outcomes with surgery. METHODS: One hundred fifty-seven patients were divided into a good nutrition group (PNI ≥40) and a poor nutrition group (PNI <40). The retrospective univariate analysis, logistic regression multivariate analysis, and receiver operating characteristic (ROC) curve analysis were used to screen out independent risk factors for postoperative complications and postoperative recurrences that required reoperation. RESULTS: Penetrating behavior was an independent risk factor for postoperative complications. Emergency surgery, penetrating behavior, hypoalbuminemia, and low PNI were independent risk factors for reoperation. By the receiver operating characteristic analysis, low PNI was superior to hypoproteinemia in predicting postsurgical recurrence. CONCLUSIONS: PNI is a good marker for predicting surgical recurrence, but it cannot predict postoperative complications. The nutritional status in patients before elective surgery can be modified to improve PNI. It can reduce surgical recurrence to a minimum level.

Nintedanib Induces the Autophagy-Dependent Death of Gastric Cancer Cells by Inhibiting the STAT3/Beclin1 Pathway.

BACKGROUND: Tyrosine kinase inhibitors are currently the most widely studied targeted therapies for gastric cancer. As a triple tyrosine inhibitor, nintedanib can alleviate the progression of a variety of cancers, but it is poorly studied in gastric cancer. AIMS: To investigate the effect of nintedanib on gastric cancer. METHODS: This study investigated nintedanib's effect on gastric cancer autophagy in vivo and in vitro, and the activity and morphological changes of gastric cancer cells were detected by MTT and HE staining. Proliferation, migration, invasion, and EMT-related marker proteins of AGS and MKN-28 cells were detected. The effects of nintedanib on autophagy in gastric cancer cells were detected by acridine orange, immunofluorescence, and Western blotting assays. The regulation of nintedanib on STAT3 and Beclin1 was detected by qPCR and Western blotting assays. Subsequently, the effects of nintedanib on the tumor STAT3/Beclin1 pathway were verified by stably overexpressing STAT3 in gastric cancer cell lines and tumor-bearing experiments in nude mice. RESULTS: The results showed that nintedanib could inhibit gastric cancer cells' proliferation and EMT process. Meanwhile, autophagy was induced in AGS and MKN-28 cells, and the expression of autophagy-related protein Beclin1 was upregulated, and the phosphorylation level of STAT3 was downregulated. Nintedanib inhibited STAT3 phosphorylation and upregulated Beclin1 to inhibit tumor growth in gastric cancer cell lines with stable STAT3 overexpression and tumor-bearing experiments in nude mice. CONCLUSIONS: By inhibiting STAT3, nintedanib upregulated Beclin1 and caused autophagic death in gastric cancer cells.

Needleless Transcutaneous Electrical Acustimulation: A Pilot Study Evaluating Improvement in Post-Operative Recovery.

BACKGROUND: Functional gastrointestinal disturbance occurs after abdominal surgeries and could last for an extended period of time in some cases. This study was designed (1) to evaluate the effects of needleless transcutaneous electrical acustimulation (TEA) on postoperative recovery, and (2) to investigate the mechanisms involving autonomic function in postoperative patients after removal of gastrointestinal cancers. METHODS: Forty-two patients (33 male, age: 69.5 ± 1.5 years) scheduled for abdominal surgical removal of gastrointestinal cancers were randomized to TEA (n = 21) and sham-TEA (n = 21). TEA was performed via acupoints ST36 and PC6 1 h twice daily from the postoperative day (POD) 1 to day 3. Sham-TEA was performed at non-acupoints. RESULTS: (1) TEA improved major postoperative symptoms by about 30%, including a reduction in time to defecation by 31.7% (P < 0.01 vs. sham-TEA), time to first flatus by 35.9% (P < 0.001), time to ambulation by 42.8% (P < 0.01), time to resuming diet by 26.5% (P < 0.01) and hospital stay by 30% (P < 0.05) as well as pain score by 50% (P < 0.01). (2) TEA significantly increased vagal activity (P < 0.001) and decreased sympathetic activity on POD 4 (P < 0.001) compared with POD 1 as well as the serum level of NE (P < 0.05). (3) The vagal activity, high frequency assessed from the spectral analysis of heart rate variability, was negatively correlated with time to resuming diet, whereas the sympathetic measurement, serum norepinephrine was positively correlated with time to resuming diet and time to flatus. (4) TEA but not sham-TEA decreased TNF-α by 17.4% from POD 1 to POD 4. (5) TEA was an independent predictor of a shorter hospital stay. CONCLUSIONS: Needleless TEA improves major postoperative symptoms by enhancing vagal and suppressing sympathetic activities.

MicroRNA-130a is upregulated in colorectal cancer and promotes cell growth and motility by directly targeting forkhead box F2.

Colorectal cancer (CRC) is one of the most prevalent cancers among males and females worldwide. Despite progress in diagnostic and therapeutic strategies for CRC patients, the prognosis for patients with advanced CRC remains poor. MicroRNAs (miRNAs/miRs) are a class of highly conserved short, endogenously expressed and single­stranded non­coding RNAs. In recent years, increasing studies have demonstrated that dysregulation of miRNAs is closely associated with CRC carcinogenesis and progression. The aim of the present study was to explore the expression, roles and underlying molecular mechanism of miR­130a in CRC. The results indicated that miR­130a was significantly upregulated in CRC, and that miR­130a expression levels were correlated with TNM stage and lymph node metastasis of CRC. Inhibition of miR­130a markedly suppressed colorectal cancer cell proliferation, migration and invasion. Furthermore, forkhead box F2 (FOXF2) was identified as a direct downstream target gene of miR­130a in colorectal cancer. Downregulation of FOXF2 could partially reverse the functions induced by miR­130a under­expression in CRC cells. These findings suggested that miR­130a can regulate FOXF2 and function as an oncogene in CRC. Therefore, miR­130a may serve as a useful therapeutic agent for miRNA­based CRC targeted therapy.

Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway.

The present study was designed to investigate the antiproliferative activity of isoimperatorin against SGC-7901 cells and to examine the possible mechanisms. The antiproliferative activity of isoimperatorin against SGC-7901 cells was evaluated using an MTT assay, and the mechanisms were investigated using flow cytometry and western blot assays, which were used to determine the apoptotic rate and expression levels of mitochondria-mediated apoptosis-associated proteins, including Survivin, myeloid leukemia cell-1 (Mcl-1), B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 (Bcl-2), second mitochondria-derived activator of caspase (Smac), Bcl-2-associated X factor (Bax), cleaved (c)-caspase-3 and c-caspase-9 in SGC-7901 cells. Additionally, a xenograft assay was used to confirm whether isoimperatorin had an inhibitory effect on SGC-7901 cell-induced tumors in vivo. The results of the MTT assay suggested that isoimperatorin significantly inhibited the proliferation of SGC-7901 cells in a dose- and time-dependent manner, and the half maximal inhibitory concentration was 18.75 µg/ml. The results of the flow cytometric analysis indicated that, following treatment with isoimperatorin, the apoptotic rate of SGC-7901 cells was significantly increased, compared with that of cells in the control group. The results of the western blot analysis indicated that, following treatment with isoimperatorin, the expression levels of the pro-apoptotic proteins, Bax, c-caspase-3 and c-caspase-9, were significantly increased and the expression levels of the anti-apoptotic proteins, Survivin and Bcl-2, were significantly reduced, compared with the control group. No alterations in expression were found in the other apoptosis-associated proteins, including Mcl-1, Bcl-xl and Smac. The results of the xenograft assay indicated that isoimperatorin significantly inhibited the growth of SGC-7901 cell-induced tumor in vivo by increasing the expression levels of pro-apoptotic proteins (Bax, c-caspase-3 and c-caspase-9) and reducing the expression levels of anti-apoptotic proteins (Survivin and Bcl-2) without adverse effects on the increasing body weight of nude mice. In conclusion, the present study revealed that isoimperatorin may be able to induce the apoptosis of SGC-7901 cells in vitro and in vivo by regulating the expression levels of mitochondria-mediated apoptosis-associated proteins.

MiR-224 promotes proliferation and migration of gastric cancer cells through targeting PAK4.

Although recent studies have shown the important role and overexpression of miR-224 in several tumors, its function in gastric cancer has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR-224 in gastric cancer, and tried to find new downstream targets of miR-224. In this study, the level of miR-224 was measured in gastric cancer cells with the normal human gastric epithelial cell. The effects of miR-224 of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, colony assay, transwell migration assay, western blotting. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-224. Overexpression of miR-224 was detected in the gastric cancer cells, especially in SCG-7901. Exogenous miR-224 expression promoted the proliferation and migration of gastric cells and abrogating expression of miR-224 suppressed proliferation, and migration of SCG-7901 cells in vitro. Luciferase assays revealed that miR-224 directly targeted the 3'UTR of p21-activated kinase 4 (PAK4). The present study provides an experimental foundation for miR-224 as a potential tumor suppressor that may decrease PAK4 expression to inhibit gastric cancer cells and that in the future, targeting of this miRNA may provide a novel strategy for the diagnosis and treatment of patients with this lethal disease.