Application Effects of NNN-link Care Model in Patients with Coronary Heart Disease.

OBJECTIVE: To investigate the effect of a NNN-linked care model applied in elderly patients with coronary heart disease. METHODS: A total of 120 elderly patients with coronary heart disease admitted to the hospital from January, 2023 to May, 2023 were randomly divided into two groups of 60 cases respectively. The control group received routine intervention, and the observation group received the NNN-linked care model. Changes in cardiac function, the ability for self-care, and quality of life were recorded between the groups before and after the intervention. RESULTS: Indices of cardiac function in the observation group were higher than those of the control group after 3 weeks (p < 0.05). Compared with the control group, the total score for the ability for self-care and the scores of each dimension of the observation group were higher after 3 weeks of intervention (p < 0.05). The scores of quality of life of the observation group were higher in comparison with the control group after 3 weeks of intervention (p < 0.05). CONCLUSION: The application of the NNN-linked care model to elderly patients with coronary heart disease can improve the ability for self-care, increase cardiac function and improve the quality of life.

Alisertib exerts KRAS allele­specific anticancer effects on colorectal cancer cell lines.

The aim of the present study was to examine the effects of alisertib (ALS) on RAS signaling pathways against a panel of colorectal cancer (CRC) cell lines and engineered Flp-In stable cell lines expressing different Kirsten rat sarcoma virus (KRAS) mutants. The viability of Caco-2KRAS wild-type, Colo-678KRAS G12D, SK-CO-1KRAS G12V, HCT116KRAS G13D, CCCL-18KRAS A146T and HT29BRAF V600E cells was examined by Cell Titer-Glo assay, and that of stable cell lines was monitored by IncuCyte. The expression levels of phosphorylated (p-)Akt and p-Erk as RAS signal outputs were measured by western blotting. The results suggested that ALS exhibited different inhibitory effects on cell viability and different regulatory effects on guanosine triphosphate (GTP)-bound RAS in CRC cell lines. ALS also exhibited various regulatory effects on the PI3K/Akt and mitogen-activated protein kinase (MAPK) pathways, the two dominant RAS signaling pathways, and induced apoptosis and autophagy in a RAS allele-specific manner. Combined treatment with ALS and selumetinib enhanced the regulatory effects of ALS on apoptosis and autophagy in CRC cell lines in a RAS allele-specific manner. Notably, combined treatment exhibited a synergistic inhibitory effect on cell proliferation in Flp-In stable cell lines. The results of the present study suggested that ALS differentially regulates RAS signaling pathways. The combined approach of ALS and a MEK inhibitor may represent a new therapeutic strategy for precision therapy for CRC in a KRAS allele-specific manner; however, this effect requires further study in vivo.

Enhanced mPGES-1 Contributes to PD-Related Peritoneal Fibrosis via Activation of the NLRP3 Inflammasome.

Background: Microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 (PGE2) is a chief mediator of inflammation. However, the role and mechanism of mPGES-1 in peritoneal dialysis (PD)-associated peritoneal fibrosis have not been investigated. Material and Methods: In PD patients, mPGES-1 expression in peritoneum tissues and the levels of PGE2, IL-1ß, and IL-18 in the dialysate were examined. In rat peritoneal mesothelial cells (RPMCs), the regulation and function of mPGES-1 and NLRP3 inflammasome were investigated. The expression of extracellular matrix proteins and the components of NLRP3 inflammasome were detected by Western blotting or real-time quantitative PCR. Results: In PD patients with ultrafiltration failure (UFF), mPGES-1 was enhanced in the peritoneum, which was associated with the degree of peritoneal fibrosis. Accordingly, the intraperitoneal PGE2 levels were also positively related to the PD duration, serum C-reactive protein levels, and serum creatinine levels in incident PD patients. In RPMCs, high-glucose treatment significantly induced mPGES-1 expression and PGE2 secretion without affecting the expressions of mPGES-2 and cPGES. Inhibition of mPGES-1 via short hairpin RNA significantly ameliorated the expression of extracellular matrix proteins of RPMCs induced by high glucose. Additionally, high glucose markedly activated NLRP3 inflammasome in RPMCs that was blunted by mPGES-1 inhibition. Furthermore, silencing NLRP3 with siRNA significantly abrogated the expression of extracellular matrix proteins in RPMCs treated with high glucose. Finally, we observed increased IL-1ß and IL-18 levels in the dialysate of incident PD patients, showing a positive correlation with PGE2. Conclusion: These data demonstrate that mPGES-1-derived PGE2 plays a critical role in PD-associated peritoneal fibrosis through activation of the NLRP3 inflammasome. Targeting mPGES-1 may offer a novel strategy to treat peritoneal fibrosis during PD.

Investigate the Effect of miR-22 on the Apoptosis of Coronary Heart Disease Cells Through the Wnt-1 Pathway Based on Nano-Silica-Induced Rat Models.

In this paper, by examining the toxicity of nano-silica to coronary heart disease cells, we explored the apoptosis of rat myocardial cells induced by nano-silica, and explored the effect of apoptosis on cells during the process of myocardial cytotoxicity induced by nano-silica. This article selects rat cardiomyocytes as the research object and conducts a group control experiment. A control group is set up with cells that are not stained with nano-silica. Different concentrations of nanosilica suspensions are applied to rat cells and detected by CCK-8 method. Cell survival rate after exposure to different concentrations of cells is used to determine the most stable exposure time and concentration. We used flow cytometry to detect intracellular reactive oxygen species and apoptotic rates, and used Western Blot to detect the expression of proteins that affect apoptosis. Finally, we investigated the effect of the Wnt signaling pathway on coronary heart disease. The Wnt signaling pathway regulates the development of the heart and blood vessels. In the treatment of cardiovascular disease, this pathway will be activated again to play a regulatory role. We conclude that nano-silica can induce cytotoxicity in rat myocardial cells through the Wnt-1 pathway, and nanosilica can induce myocardial cell apoptosis through the Wnt-1 pathway.

Study on the association between IL-1ß, IL-8 and IL-10 gene polymorphisms and risk of coronary artery disease.

We aimed to evaluate the role of genetic polymorphisms in IL-1ß, IL-8 and IL-10 in the risk of coronary artery disease (CAD). We identified 325 patients with CAD and 342 control subjects without CAD between January 2013 and December 2014. Genotyping of IL-1ß +3954 C/T, IL-1ß -511 C/T, IL-8-251T/A, IL-10-1082A/G and IL-10-819C/T was performed in a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). By Multivariate logistic regression analysis, the GG and AG+GG genotypes of IL-10-1082A/G were significantly associated with an increased risk of CAD. The ORs (95% CI) for GG and AG+GG genotypes were 2.12 (1.32-3.43) and 1.56 (1.14-2.14), respectively. Patients carrying the AG+GG genotype of IL-10-1082A/G was associated with an increased risk of CAD in those with hypertension, diabetes mellitus and smokers, and the ORs (95% CI) were 1.41 (0.93-2.14), 7.13 (2.28-23.56) and 2.12 (1.17-3.89), respectively. Our study found that IL-10-1082A/G polymorphism is associated with an increased risk of CAD, especially in hypertension, diabetes mellitus and smokers.

Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.

[Effect of perioperative intestinal probiotics on intestinal flora and immune function in patients with colorectal cancer].

OBJECTIVE: To investigate the effect of perioperative application of intestinal probiotics to substitute oral intestinal antimicrobial agents on intestinal flora and immune function in surgical patients with colorectal cancer. METHODS: Sixty patients with colorectal cancer undergoing elective laparoscopic radical surgery were randomized to receive preoperative bowel preparation using oral intestinal antimicrobial agents (n=20) or using oral intestinal probiotics (Jinshuangqi Tablets, 2.0 g, 3 times daily) since the fifth day before the operation and at 24 h after the operation for 7 consecutive days. Upon admission and 7 days after the operation, fecal samples and fasting peripheral venous blood were collected from the patients to examine the intestinal flora and serum levels of interleukin-2 (IL-2), IgA, IgG, and IgM, NK cell activity, T lymphocytes subsets CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) ratio. RESULTS: At 7 days after the operation, the patients receiving probiotics showed significantly increased counts of intestinal Bifidobacterium, Lactobacillus, and Enterococcus (P<0.05) and significantly lowered counts of Escherichia coli and Staphylococcus aureus (P<0.05). The serum levels of IL-2, IgA, IgG and IgM as well as CD4(+) cell percentage all increased significantly in probiotics group compared with those in patients with conventional intestinal preparation (P<0.05). CONCLUSIONS: Perioperative application of intestinal probiotics to replace preoperative oral intestinal antimicrobial agents can effectively correct intestinal flora imbalance and improve the immune function of surgical patients with colorectal cancer.

[Laparoscopic anterior resection of rectal carcinoma with preservation of the left colonic artery].

OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopic anterior resection of rectal carcinoma with preservation of the left colonic artery. METHODS: From February 2006 to February 2009, 52 patients with rectal carcinoma formerly scheduled for Dixon operation (clinical stage I and II) received laparoscopic Dixon surgery. The inferior mesenteric artery, left colonic artery, sigmoid artery or superior rectal artery, and lymph nodes were dissected through the vasa vasorum approach. The left colonic artery was retained by transecting the inferior mesenteric artery inferior to the left colonic artery. The operative time, intraoperative hemorrhage volume, intraoperative complications, anastomotic tension, number and histopathological features of the dissected lymph nodes surrounding the inferior mesenteric artery, and the rates of local recurrence, lymph node metastasis and anastomotic leakage were analyzed. RESULTS: The operation was successfully completed in all the 52 cases. The operative time ranged from 115 to 320 min with a mean of 150 min. The mean intraoperative hemorrhage was 25 ml (range 15-75 ml). None of the patients had perforation of the rectum, injuries to blood vessel, ureter or adjacent organs, or anastomotic tension. The number of dissected lymph nodes surrounding the inferior mesenteric artery ranged from 4 to 8, with a mean of 6.2. The dissected lymph nodes in the base of the inferior mesenteric artery showed no cancer cell metastasis, while 4 patients had cancer cell metastasis in the lymph nodes surrounding superior rectal artery. None of patients had anastomotic leakage. Local recurrence was found in only 1 case at 7 months after the operation. CONCLUSION: Laparoscopic anterior resection of the rectal carcinoma with preservation of the left colonic artery can be completed in patients with rectal carcinoma planning to receive Dixon operation (clinical stage I or II). This surgical approach preserves more supplying vessels and prevents anastomotic leakage without increasing the anastomotic tension or affecting lymph node dissection surrounding the inferior mesenteric artery.

[Endoscopic and histopathological features of serrated adenoma of large intestine:an analysis of 71 cases].

OBJECTIVE: To explore the endoscopic and histopathological morphology of large intestinal serrated adenomas (SA). METHODS: The endoscopic and pathological data of 71 SA patients, diagnosed in the Digestive Endoscopy Center, Nanfang Hospital from January 2002 to July 2005, were analyzed retrospectively. RESULTS: Forty-seven of the 71 serrated adenomas were protruded (sessile 23, semipedunculated 5, pedunculated 23) and 24 were superficial (flat 16, laterally spreading 8). The mean sizes of the protruded and superficial SA were 10.5 mm and 16.6 mm, respectively, and both of them were frequently located in the sigmoid and rectum. Histopathologically, SA contained tubular glands in 53, tubulovillous glands in 9 and villous glands in 9 cases. Mild dysplasia was found in 47 SAs, moderate dysplasia in 22 SAs, and canceration foci in 2 SAs. The dysplasia of SAs (<10 mm) was significantly better than that of SAs (>or= 10 mm) (P< 0.01). Most IV and III L pit SAs presented villous glands (64%) and tubular glands (68%), respectively. 40% of hyperplastic polyps-like SAs, composed of tubular glands,showed II pit pattern. Atypia in II pit SAs was similar to that in IIIL pit SAs, but was worse than that in IV pit SAs. CONCLUSION: Polyps with II pit pattern possibly are SAs sometimes. SA with the common characters of neoplastic polyps,should be regarded as a new potential precancerous lesion.