[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.

[Advances in cardiovascular protection effects and mechanisms of allicin].

Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.

[Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification].

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Clinical implications of cytogenetic heterogeneity in Philadelphia chromosome positive (Ph+) adult B cell acute lymphoblastic leukemia following tyrosine kinase inhibitors and chemotherapy regimens.

We retrospectively studied a cohort of 144 adults with Philadelphia chromosome/BCR-ABL1 positive B acute lymphoblastic leukemia (Ph + B-ALL) to assess the clinical implications of cytogenetic heterogeneity in this disease. The study group included 85 men and 59 women that were sorted into 6 subgroups based on karyotypic findings in the stemline as follows: 32 patients with t(9;22) as a sole aberration, 23 with t(9;22) plus 1 additional chromosomal abnormality (ACA), 26 with t(9;22) as part of a complex karyotype, 18 showing a variant-/complex- t(9;22), 30 with t(9;22) as the stemline with ACAs in the sideline(s), and 15 patients who had the t(9;22) and hyperdiploidy. In 89 patients 1 clone was identified; 41 had 2 clones and 14 had ≥ 3 clone(s). The median overall survival (OS) was 25.6 months and the median relapse-free survival (RFS) was 20.6 months. Patients with variant-/complex- t(9;22) had poorer OS and RFS when compared with all other subgroups combined (P = 0.0018 and P = 0.0049, respectively). In addition, patients with ≥ 2 clones had worse OS and RFS than patients with 1 clone (P = 0.0179 and P = 0.0429, respectively). Multivariate analysis confirmed that variant-/complex-t(9;22) and clone number are independent risk factors. We suggest that conventional chromosomal analysis is of clinical importance for risk stratification of B-ALL patients.

Depsidone Derivatives and a Cyclopeptide Produced by Marine Fungus Aspergillus unguis under Chemical Induction and by Its Plasma Induced Mutant.

A new depsidone derivative (1), aspergillusidone G, was isolated from a marine fungus Aspergillus unguis, together with eight known depsidones (2‒9) and a cyclic peptide (10): agonodepside A (2), nornidulin (3), nidulin (4), aspergillusidone F (5), unguinol (6), aspergillusidone C (7), 2-chlorounguinol (8), aspergillusidone A (9), and unguisin A (10). Compounds 1‒4 and 7‒9 were obtained from the plasma induced mutant of this fungus, while 5, 6, and 10 were isolated from the original strain under chemical induction. Their structures were identified using spectroscopic analysis, as well as by comparison with literature data. The HPLC fingerprint analysis indicates that chemical induction and plasma mutagenesis effectively influenced the secondary metabolism, which may be due to their regulation in the key steps in depsidone biosynthesis. In bioassays, compound 9 inhibited acetylcholinesterase (AChE) with IC50 in 56.75 µM. Compounds 1, 5, 7, 8, and 9 showed moderate to strong activity towards different microbes. Compounds 3, 4, and 5 exhibited potent larvicidality against brine shrimp. In docking studies, higher negative CDOCKER interaction energy and richer strong interactions between AChE and 9 explained the greater activity of 9 compared to 1. Chemical induction and plasma mutagenesis can be used as tools to expand the chemodiversity of fungi and obtain useful natural products.

Comparison of Arthrodesis and Non-fusion to Treat Lisfranc Injuries.

OBJECTIVE: "Lisfranc joint injury" is comprised of a tarsometatarsal joint-complex injury. The Lisfranc complex injury is always a challenge for orthopedists, and the optimum treatment is still up for debate. Anatomic reduction and stable internal fixation prove to have no satisfactory outcomes. This research aims to compare the clinical curative effects, complications and radiographic features of arthrodesis and non-fusion of the Lisfranc joint in the follow-up of the patients who suffered Lisfranc injuries. METHODS: A comparative retrospective study of 25 patients with acute or subacute Lisfranc complex injuries was conducted between September 2013 and March 2015 in the First Affiliated Hospital of Soochow University. All patients were classified by Myerson classification. Eight patients were treated with arthrodesis, while 17 patients received non-fusion operations. The clinical curative effects, complications and image differences were compared between the two groups. American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, Short Form-36 (SF-36) and Visual Analogue Scale (VAS) score were evaluated for each patient during the follow-up. All statistics were analyzed using the SPSS software system. RESULTS: All fractures healed for both the arthrodesis group and the non-fusion group. Patients in the arthrodesis group had a higher AOFAS score compared with patients in the non-fusion group (94.00 vs. 88.58, P = 0.034). Complications occurred in eight patients (8/17, 47%) in the non-arthrodesis group, including the second and third phalanx abduction (1), talipes cavus (2), eversion deformity of front foot (3), eversion deformity of calcaneus (1), as well as postoperative infection (1). Only two patients (2/8, 25%) in the arthrodesis group suffered complications. One was a limitation of motion of the front foot and pain during walking; the other was an eversion deformity of front foot. CONCLUSION: Primary arthrodesis has advantages compared to primary open reduction and internal fixation (ORIF): reduced foot deformity rates, sustained biomechanical morphology of the feet, reduced complications, higher level of function recovery, shorter time of surgical procedures, fewer complications, higher AOFAS score and fewer frequency of complications. According to our research, primary arthrodesis may be a better choice for treating Lisfranc injury.

A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1.

Four quinolinones (1-4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. In addition, five new quinolinone derivatives (5-9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC50-24 h of 8.4 µg/mL and 30.7 µg/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.