[Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria].

OBJECTIVE: To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate. METHODS: The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated. RESULTS: There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively. CONCLUSION: The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology.

Chitosan is increasingly used for safe nucleic acid delivery in gene therapy studies, due to well-known properties such as bioadhesion, low toxicity, biodegradability and biocompatibility. Furthermore, chitosan derivatization can be easily performed to improve the solubility and stability of chitosan-nucleic acid polyplexes, and enhance efficient target cell drug delivery, cell uptake, intracellular endosomal escape, unpacking and nuclear import of expression plasmids. As in other fields, chitosan is a promising drug delivery vector with great potential for the fish farming industry. This review highlights state-of-the-art assays using chitosan-based methodologies for delivering nucleic acids into cells, and focuses attention on recent advances in chitosan-mediated gene delivery for fish biotechnology applications. The efficiency of chitosan for gene therapy studies in fish biotechnology is discussed in fields such as fish vaccination against bacterial and viral infection, control of gonadal development and gene overexpression and silencing for overcoming metabolic limitations, such as dependence on protein-rich diets and the low glucose tolerance of farmed fish. Finally, challenges and perspectives on the future developments of chitosan-based gene delivery in fish are also discussed.

Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer.

Colorectal cancer (CRC) is one of the major health threats in developed countries. Changes in dietary components, such as more protein and lipid intake, can increase the risk of CRC. Diet affects CRC in many ways. They regulate the composition and function of gut microbiota, which have an amazing metabolic capacity and can produce short chain fatty acids (SCFAs), such as propionate, acetate, and butyrate. Butyrate is a principal energy source for colonic epithelial cells and plays an important role in maintaining the stability of gut microbiota and the integrity of intestinal epithelium. However, there are few studies reviewing the anti-CRC potentials of butyrate. This review summarizes the recent research progresses in the effect of gut microbiota imbalance and the decrease in intestinal microbial metabolite butyrate caused by unbalanced diet on CRC development, and discusses the mechanisms of butyrate-induced anti-CRC activities, which may guide people to prevent CRC by improving diet structures.

The anticancer functions of RIG-I-like receptors, RIG-I and MDA5, and their applications in cancer therapy.

Cancer is a major cause of death worldwide, and its incidence and mortality continuously increase in China. Nowadays, cancer heavily influences our health and constitutes enormous burden on society and families. Although there are many tools for cancer treatment, but the overall therapeutic effect is poor. In addition, cancer cells often develop resistance to therapy due to defective cell death or immune escape mechanisms. Therefore, it is a promising way for cancer treatment to effectively activate apoptosis and conquer immunosuppression. RIG-I-like receptors (RLRs) belong to RNA-sensing pattern recognition receptors (PRRs), one of the major subsets of PRRs, and play a critical role in sensing RNA viruses and initiate host antiviral responses such as the production of type I interferons (IFNs), proinflammatory cytokines, and other immune response molecules. Recent studies have demonstrated that tumor cells could mimic viral infection to activate viral recognition of immune system and the activation of interferon response pathway. RIG-I and MDA5, two members of RLRs family, could induce growth inhibition or apoptosis of multiple types of cancer cells on the activation by RNA ligands in IFN-dependent or IFN-independent approach. Previous studies have reviewed PRRs as promising immunotherapy targets for colorectal cancer and pancreatic cancer. However, until now, a comprehensive review on the role of RLRs in the development and treatment of various cancers is still lacking. In this article, we reviewed the latest studies on the roles as well as the mechanisms of RIG-I and MDA5 in the development of various cancers and therapeutic potentials of targeting RIG-I and MDA5 for cancer treatment.

Nucleic acid sensing pattern recognition receptors in the development of colorectal cancer and colitis.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36). Activation of these receptors eventually leads to the release of cytokines and activation of immune cells, which are well known to play crucial roles in host defense against intracellular bacterial and virus infection. However, the functions of these nucleic acid sensing PRRs in the other diseases such as CRC and colitis remain largely unknown. Recent studies indicated that nucleic acid sensing PRRs contribute to CRC and/or colitis development, and therapeutic modulation of nucleic acid sensing PRRs may reduce the risk of CRC development. However, until now, a comprehensive review on the role of nucleic acid sensing PRRs in CRC and colitis is still lacking. This review provided an overview of the roles as well as the mechanisms of these nucleic acid sensing PRRs (AIM2, STING, cGAS, RIG-I and its downstream molecules, DDX3, 5, 6,17, and DHX9, 36) in CRC and colitis, which may aid the diagnosis, therapy, and prognostic prediction of CRC and colitis.