Liaoning Vocational College of Medical

The immunosuppressive tumor microenvironment and poor drug targeting remain major obstacles in bladder cancer (BC) therapy. To address this, a combination strategy integrating chemotherapy and immunotherapy was employed by co-delivering epirubicin (EPI) and the immune modulator imiquimod (IMQ) using a folate-modified nanocarrier. A hydroxyethyl starch-based epirubicin prodrug modified with folic acid (FA-HES-EPI) was first synthesized to improve tumor selectivity. FA-HES-EPI/IMQ micelles were then fabricated via nanoprecipitation by encapsulating IMQ into the hydrophobic core, aiming to achieve synergistic therapeutic efficacy. Folate modification conferred tumor-targeting capability to the micelles and promoted efficient cellular uptake via folate receptor-mediated endocytosis. The acid-sensitive hydrazone bond enabled controlled release of both EPI and IMQ in the acidic tumor microenvironment, thereby enhancing their combined chemo-immunotherapeutic effects. In an orthotopic BC model, FA-HES-EPI/IMQ micelles significantly enhanced drug accumulation at the tumor site, repolarized M2-type tumor-associated macrophages (TAMs) toward the M1 phenotype, remodeled the tumor stroma, and achieved a tumor inhibition rate of 96.7%, markedly surpassing that of FA-HES-EPI micelles (86.6%) and free EPI (62.3%), with negligible systemic toxicity. This pH-responsive co-delivery system represents a promising approach to improve both efficacy and safety in bladder cancer treatment.

Pharmacological studies have shown that Cedrol (CE) exhibits extensive biological activities, including anti-inflammatory and analgesic. Moreover, it can inhibit the NF-κB pathway and the expression of various associated proteins. This study aimed to investigate the role of CE in postmenopausal osteoporosis. The results showed that intragastric administration of CE (10 and 20mg/kg) significantly improved the bone microstructure damage and increased bone mineral density, trabecular bone volume, and bone trabecular thickness in ovariectomized (OVX) rats (p < 0.05). CE treatment additionally made a well-organized arrangement of bone trabeculae and improved its thickness and density. Compared with the OVX group, the levels of tartrate-resistant acid phosphatase from 5b and C-terminal telopeptide of type I collagen were significantly reduced by 42.75% and 49.27% in the OVX + CE rats (p < 0.05). TRAP staining visually showed that the number of osteoclasts in the femur tissue of CE-treated rats was less than that of the OVX group. The expressions of nuclear factor of activated T-cells, cytoplasmic 1, acid phosphatase 5, and cathepsin K in OVX + CE rats were significantly decreased by 51.61%, 46.07%, and 50.34% compared to the OVX group (p < 0.01). In addition, CE intervention effectively reduced the phosphorylation levels of P65 and IκBα and inhibited the NF-κB signaling pathway. Meanwhile, CE diminished the number of multinucleated osteoclasts induced by receptor activator for nuclear factor-κB ligand and hindered cell fusion as well as nuclear translocation of osteoclast precursor cells P65. In conclusion, CE inhibits osteoclastogenesis by suppressing the activation of the NF-κB signaling pathway, thereby alleviating postmenopausal osteoporosis.

Objective To investigate the clinical effects and advantages of flexible 3D laparoscopic surgery on rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods The data of 152 patients who received laparoscopic rectal cancer resection after nCRT excluding the cases of high rectal cancer, cardiac and pulmonary dysfunction were analyzed from January 2015 to January 2016 in the Department of Colorectal Surgery of Liaoning Cancer Hospital. The distances from the annal edge to the inferior tumor margin were within 8 cm in these patients. Among these patients, 76 cases received the 3D laparoscopic surgery after nCRT (3D-nCRT), and 76 cases undergone the 2D laparoscopic surgery after nCRT (2D-nCRT). Results Between two groups, the number of lymph node harvest (14.8±2.1 vs. 14.3±1.7), positive rate of the distal margin [1.3% (1/76) vs. 2.6% (2/76)], reserving anus rate [92.1% (70/76) vs. 81.2% (67/76)], local recurrence rate [1.3% (1/76) vs. 3.9% (3/76)] and anastomotic leakage rate [2.6% (2/76) vs. 3.9% (3/76)] had no statistical differences (all P > 0.05), while the operative time [(125.3±10.2) min vs. (136.6±12.0) min], intraoperative bleeding [(54.1±23.2) ml vs. (61.9±19.5) ml], anus exhaust time [(43.5±5.0) h vs. (45.4±5.6) h] and positive rate of circumferential resection margin (CRM) [1.3% (1/76) vs. 9.2% (7/76)] had statistical differences (all P < 0.05). Conclusion Flexible 3D laparoscopic surgery on rectal cancer after nCRT can shorten operative time, reduce intraoperative bleeding, alleviate the influence of intestinal peristalsis function,and improve operative quality. Key words: 3D Laparoscopy; Rectal neoplasms; Laparoscopic surgery; Neoadjuvant chemoradiotherapy; Surgical procedures, minimally invasive

Analysis of published data provided evidence that the main candidates for the role of the end effector for ischemic postconditioning of the heart are: 1) BK-type K+ channels (big conductance K+ channels); 2) mitochondrial ATP-sensitive K+ channels; and 3) MPT pores (mitochondrial permeability transition pores). However, some investigators believe that mitoKATP channels constitute no more than an intermediate link in the chain of signal events mediating increases in the tolerance of the heart to the actions of ischemia-reperfusion. Of these three structures, MPT pores are the most likely end effector. However, it remains possible that there is no unique molecular complex which is the sole end effector of postconditioning. It may be that there are several effectors mediating the cardioprotective effects of the adaptive postconditioning phenomenon.

The molecular mechanism underlying the proliferation of colorectal cancer (CRC) cells is not completely understood. Here, we found that the level of neuregulin receptor degradation protein-1 (Nrdp1) E3 ubiquitin ligase was significantly decreased in CRC tissues, compared with the adjacent normal tissues from human patients. Knockdown of Nrdp1 enhanced the proliferation of CRC cells, while overexpression of Nrdp1 inhibited the proliferation of CRC cells. Further analysis showed that Nrdp1 may induce degradation of its target ErbB3 to inhibit activation of both ERK/MAPK and PI3K/Akt pathways in CRC cells, which seemed to affect cell proliferation via nuclear retention of a major cell-cycle inhibitor, p27. Taken together, these findings suggest that Nrdp1-mediated ErbB3 degradation suppresses cellular growth of CRC and that Nrdp1 loss in CRC may promote tumor progression, thus highlighting Nrdp1 as a novel target for CRC therapy.

This study aims to investigate adverse reactions caused by antibiotics, and promote clinically safe, effective and rational use of antibiotics. Data on antibiotic use were obtained from the First Affiliated Hospital of Liaoning Medical College&nbsp;of&nbsp;China from September 2009 to May 2010, summarized and statistical analyses were carried out respectively on antibiotic dosage, times of adverse reactions caused by antibiotics, drug administration routes and drug forms. The findings of this research revealed that antibiotics have many adverse reactions, but they can be prevented and controlled, and we should pay attention to clinical monitoring during drug use. Hence only safe, effective and rational use of antibiotics can effectively show the efficacy and reduce the incidence of adverse reactions. &nbsp; Key words:&nbsp;Antibiotics, adverse reaction, clinical application.