Molecular phylogeny and morphology of Sporodiniella sinensis sp. nov. (Syzygitaceae, Mucorales), an invertebrate-associated species from Yunnan, China.

During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62 % for internal transcribed spacer (ITS), 98.66-99.10 % for ribosomal small subunit (nrSSU), and 96.36-98.22 % for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.

A coupling model based on spatial characteristics and evolution of terrestrial ecosystem carbon storage: a case study of Hanzhong.

Ecosystem carbon storage (ECS) is a critical consideration in reducing the impact of global warming and tackling environmental challenges, positioning it at the forefront of contemporary research. Due to the significant differences in the influence of land usage patterns on ECS in various policy contexts and China's commitment to attaining a carbon-neutral status, a model simulating different scenarios is needed to analyze the spatiotemporal characteristics and evolutionary process of carbon storage in terrestrial ecosystems accurately. To address this challenge, this study established a coupling model of "Geographical analysis -Evolution analysis -Predicting (GEP)" for assessing ecosystem ECS and analyzing its spatial characteristics and evolutionary patterns and projecting the spatial distribution of ECS under various developmental scenarios, which analyzed variations in ECS across different levels of magnitude and delineated the changing areas across a range of varying scenarios in the future additionally. The outcomes suggested that the ECS decreased by 1.17 × 106 t from 1990 to 2020, which pertaining to the utilization transfer of land in the area, whose change in ECS levels with a positive trend. It is predicted that the ECS will grow by 1.15 × 106 t and 1.44 × 106 t, in 2030 and 2060 compared with 2020 within the framework of natural development scenario (NDS), while within the framework of ecological protection scene (EPS), ECS will increase significantly, increasing by 3.06 × 106 t and 4.44 × 106 t. There will be more areas where ECS increases within the framework of EPS, by comparing with the NDS. This study offers a comprehensive analysis of Hanzhong City's carbon storage trends, demonstrating its significant impact on climate change mitigation and serving as a predictive model for similar regions, which underscores the importance of localized carbon management strategies, offering valuable insights for local governments in formulating effective climate adaptation and mitigation policies.

Molecular phylogeny and morphology reveal two new entomopathogenic species of Ophiocordyceps (Ophiocordycipitaceae, Hypocreales) parasitic on termites from China.

Two new termite-pathogenic species, Ophiocordycepsglobiperitheciata and O.longistipes, are described from Yunnan Province, China. Six-locus (ITS, nrSSU, nrLSU, tef-1α, rpb1 and rpb2) phylogenetic analyses in combination with morphological observations were employed to characterize these two species. Phylogenetically, O.globiperitheciata is most closely related to Hirsutellacryptosclerotium and O.communis, whereas O.longistipes shares a sister relationship with O.fusiformis. However, O.globiperitheciata differs from H.cryptosclerotium by parasitizing Blattodea and producing clavate, unbifurcated stromata. Ophiocordycepsglobiperitheciata is distinguished from O.communis by multiple stromata, shorter asci and ascospores. Ophiocordycepslongistipes differs from O.fusiformis in producing larger stromata, perithecia, asci and ascospores, as well as smaller citriform or oval conidia. Morphological descriptions of the two new species and a dichotomous key to the 19 termite-pathogenic Ophiocordyceps species are presented.

Supramolecular Chemotherapy: Complexation by Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Nitrogen Mustard to Normal Cells and Enhancing Its Antitumor Efficiency against Breast Cancer.

Advances in chemotherapeutic strategies are urgently required to improve antitumor efficiency. Herein, a carboxylated pillar[6]arene (CP6A) was employed to load chemotherapy medication, nitrogen mustard (NM), via forming a direct host-guest complex, as this helps to decrease the cytotoxicity of NM on normal mammary epithelial cells. Attributed to the stronger complexation ability of CP6A for endogenous spermine (SPM) than for NM, the complexed NM could be competitively released from the CP6A cavity via replacement with SPM. This chemotherapy strategy performed well in vitro and in vivo for SPM-overexpressed cancers. In comparison with free NM, antitumor efficiency of NM/CP6A was significantly enhanced, which originated from the synergistic effect of competitive release of NM and simultaneous trapping of SPM. This strategy might guide expansion to other first-line antitumor agents to improve therapeutic efficacy and decrease side effects, thereby replenishing the possibilities of supramolecular chemotherapy.

Anomalous anti-Kasha excited-state luminescence from symmetry-breaking heterogeneous carbon bisnanohoops.

It is a long-standing scientific controversy to achieve anti-Kasha-type multiple emissions by tuning the structures at a molecular level. Although it is known that some conjugated structures have excitation-dependent multiple emissions, no all-benzenoid molecules have yet been reported, the emissions of which originate from different excited states. Herein, we report the design of two symmetry-breaking heterogeneous carbon bisnanohoops that in solution become multiple fluorescent emitters with unusual anti-Kasha characteristics. This phenomenon can be spectroscopically and theoretically explained and will find applications in a wide range of sensing and imaging technologies.

Energy and Speed Landscapes of the Membrane Internalization Behavior of Soft Nanoparticles.

The cellular endocytosis of nanoparticles (NPs) is a fundamental biological process with significant potential in biomedical applications. However, a comprehensive understanding of the mechanistic aspects of endocytosis and the impact of particle properties on this process remains elusive. In this study, we investigated the membrane-wrapping behavior of soft NPs (SNPs) with varying rigidities using theoretical calculations. Our findings reveal that the membrane-wrapping process of SNPs involves a complex energy change including the possible existence of an energy barrier; moreover, it is found that the location and height of this barrier strongly depend on the mechanistic properties of the NPs and membranes. Additionally, by considering force balance in the membrane-wrapping process, we calculated the speed at which NP is internalized by the membrane, showing a nonmonotonic dependence on particle rigidity and/or wrapping degree. These phenomena can be attributed to competition between different energy components associated with NP-membrane binding, membrane tension, and deformations occurring during SNP-membrane interaction processes. Our results contribute to a deeper understanding of cellular-level endocytosis mechanisms and offer potential applications for soft NPs in biomedicine.

Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation.

The Greatwall-family protein kinase Rim15 is associated with the nutrient starvation response, whereas its role in oxidative stress responses remains unclear. Here, acetic acid and peroxide were used as two oxidative stress elicitors. The antioxidant indicator assay under acetic acid stress revealed the impaired growth in rim15Δ related to the regulation of antioxidant systems. Comparative transcriptome analysis revealed that differentially expressed genes (DEGs) are predicted to be mostly regulated by oxidative stress-responsive transcriptional factor Yap1. Among the DEGs, acetic acid stress-induced genes were found, and YAP1 disruption also inhibited their induction. The deletion of Rim15 or the Rim15 kinase domain in yap1Δ did not further decrease the gene expression, suggesting that Rim15 functions together with Yap1 in regulating acetic acid stress-induced genes, which requires Rim15 kinase activity. Additionally, Rim15 regulated H2O2 stress tolerance through partially similar but special mechanisms in that Rim15 kinase activity impacted acetic acid and H2O2 stress tolerance in different degrees, indicating the different mechanisms underlying Rim15-mediated redox regulation against different stressors. These results benefit the better understanding of stress signaling pathways related to Rim15. Given that Rim15 and some of its target genes are conserved across eukaryotes, these results also provide a basis for studies of oxidative stress-related processes in other organisms.

Klebicin E, a pore-forming bacteriocin of Klebsiella pneumoniae, exploits the porin OmpC and the Ton system for translocation.

Bacteriocins, which have narrow-spectrum activity and limited adverse effects, are promising alternatives to antibiotics. In this study, we identified klebicin E (KlebE), a small bacteriocin derived from Klebsiella pneumoniae. KlebE exhibited strong efficacy against multidrug-resistant K. pneumoniae isolates and conferred a significant growth advantage to the producing strain during intraspecies competition. A giant unilamellar vesicle leakage assay demonstrated the unique membrane permeabilization effect of KlebE, suggesting that it is a pore-forming toxin. In addition to a C-terminal toxic domain, KlebE also has a disordered N-terminal domain and a globular central domain. Pulldown assays and soft agar overlay experiments revealed the essential role of the outer membrane porin OmpC and the Ton system in KlebE recognition and cytotoxicity. Strong binding between KlebE and both OmpC and TonB was observed. The TonB-box, a crucial component of the toxin-TonB interaction, was identified as the 7-amino acid sequence (E3ETLTVV9) located in the N-terminal region. Further studies showed that a region near the bottom of the central domain of KlebE plays a primary role in recognizing OmpC, with eight residues surrounding this region identified as essential for KlebE toxicity. Finally, based on the discrepancies in OmpC sequences between the KlebE-resistant and sensitive strains, it was found that the 91st residue of OmpC, an aspartic acid residue, is a key determinant of KlebE toxicity. The identification and characterization of this toxin will facilitate the development of bacteriocin-based therapies targeting multidrug-resistant K. pneumoniae infections.

Transcatheter arterial embolization with N-butyl cyanoacrylate for postoperative hemorrhage treatment following pancreatoduodenectomy.

PURPOSE: Postoperative hemorrhage (PPH) is a severe complication of pancreatoduodenectomy (PD) with a mortality rate of 5-20.2% and mortality due to hemorrhage of 11-58%. Transcatheter arterial embolization (TAE) has been widely recommended for PPH, however, TAE with N-butyl cyanoacrylate (NBCA) for PPH treatment has been reported rarely. Therefore, this study aimed to evaluate the safety and efficacy of TAE with NBCA for PPH treatment following PD. METHODS: This retrospective study included 14 male patients (mean age, 60.93 ± 10.97 years) with postoperative hemorrhage following PD treated with TAE using NBCA as the main embolic agent from October 2019 to February 2022. The clinical data, technical and success rate, and complications were analyzed. RESULTS: Among the 14 patients who underwent TAE, the technical and clinical success rates were 100 and 85.71%, respectively. Angiography revealed contrast extravasation in 12 cases and a pseudoaneurysm in 3 cases. One patient developed a serious infection and died 2 days after the TAE. CONCLUSION: TAE with NBCA for PPH treatment following PD, especially for massive hemorrhage caused by a pancreatic fistula, biliary fistula, or inflammatory corrosion, can result in rapid and effective hemostasis with high safety.

Regulatory mechanisms underlying yeast chemical stress response and development of robust strains for bioproduction.

Yeast is widely studied in producing biofuels and biochemicals using renewable biomass. Among various yeasts, Saccharomyces cerevisiae has been particularly recognized as an important yeast cell factory. However, economic bioproduction using S. cerevisiae is challenged by harsh environments during fermentation, among which inhibitory chemicals in the culture media or toxic products are common experiences. Understanding the stress-responsive mechanisms is conducive to developing robust yeast strains. Here, we review recent progress in mechanisms underlying yeast stress response, including regulation of cell wall integrity, membrane transport, antioxidative system, and gene transcription. We highlight epigenetic regulation of stress response and summarize manipulation of yeast stress tolerance for improved bioproduction. Prospects in the application of machine learning to improve production efficiency are also discussed.

Emergence and Causality in Complex Systems: A Survey of Causal Emergence and Related Quantitative Studies.

Emergence and causality are two fundamental concepts for understanding complex systems. They are interconnected. On one hand, emergence refers to the phenomenon where macroscopic properties cannot be solely attributed to the cause of individual properties. On the other hand, causality can exhibit emergence, meaning that new causal laws may arise as we increase the level of abstraction. Causal emergence (CE) theory aims to bridge these two concepts and even employs measures of causality to quantify emergence. This paper provides a comprehensive review of recent advancements in quantitative theories and applications of CE. It focuses on two primary challenges: quantifying CE and identifying it from data. The latter task requires the integration of machine learning and neural network techniques, establishing a significant link between causal emergence and machine learning. We highlight two problem categories: CE with machine learning and CE for machine learning, both of which emphasize the crucial role of effective information (EI) as a measure of causal emergence. The final section of this review explores potential applications and provides insights into future perspectives.

Differential Protein Expression in Set5p-Mediated Acetic Acid Stress Response and Novel Targets for Engineering Yeast Stress Tolerance.

Acetic acid is a prevalent inhibitor in lignocellulosic hydrolysate, which represses microbial growth and bioproduction. Histone modification and chromatin remodeling have been revealed to be critical for regulating eukaryotic metabolism. However, related studies in chronic acetic acid stress responses remain unclear. Our previous studies revealed that overexpression of the histone H4 methyltransferase Set5p enhanced acetic acid stress tolerance of the budding yeast Saccharomyces cerevisiae. In this study, we examined the role of Set5p in acetic acid stress by analyzing global protein expression. Significant activation of intracellular protein expression under the stress was discovered, and the functions of the differential proteins were mainly involved in chromatin modification, signal transduction, and carbohydrate metabolism. Notably, a substantial increase of Set5p expression was observed in response to acetic acid stress. Functional studies demonstrated that the restriction of the telomere capping protein Rtc3p, as well as Ies3p and Taf14p, which are related to chromatin regulation, was critical for yeast stress response. This study enriches the understanding of the epigenetic regulatory mechanisms underlying yeast stress response mediated by histone-modifying enzymes. The results also benefit the development of robust yeast strains for lignocellulosic bioconversion.

Cholesterol Depletion and Membrane Deformation by MeßCD and the Resultant Enhanced T Cell Killing.

Recent studies have demonstrated the crucial role of cholesterol (Chol) in regulating the mechanical properties and biological functions of cell membranes. Methyl-ß-cyclodextrin (MeßCD) is commonly utilized to modulate the Chol content in cell membranes, but there remains a lack of a comprehensive understanding. In this study, using a range of different techniques, we find that the optimal ratio of MeßCD to Chol for complete removal of Chol from a phosphocholine (PC)/Chol mixed membrane with a 1:1 mol ratio is 4.5:1, while the critical MeßCD-to-Chol ratio for membrane permeation falls within the range between 1.5 and 2.4. MeßCD at elevated concentrations induces the formation of fibrils or tubes from a PC membrane. Single lipid tracking reveals that removing Chol restores the diffusion of lipid molecules in the PC/Chol membrane to levels observed in pure PC membranes. Exposure to 5 mM MeßCD for 30 min effectively eliminates Chol from various cell lines, leading to an up to 8-fold enhancement in melittin cytotoxicity over Hela cells and an up to 3.5-fold augmentation of T cell cytotoxicity against B16F10-OVA cells. This study presents a diagram that delineates the concentration- and time-dependent distribution of MeßCD-induced Chol depletion and membrane deformation, which holds significant potential for modulating the mechanical properties of cellular membranes in prospective biomedical applications.

Asymmetric disturbance and permeabilization of bilayer membranes by 3-nm carbon dots.

Small-sized fluorescent carbon dots (CDs) are gaining increasing attention in the field of biomedical applications. The environmental and biological compatibility of positively charged CDs has been extensively investigated; however, the potential cytotoxicity caused by negatively and particularly neutrally charged small CDs has been significantly overlooked. In this study, we conducted a comprehensive investigation into the cellular membrane disruption effect of weakly negatively charged 3-nm CDs using a combination of various biophysical techniques. Our findings demonstrate that even at a low concentration of 0.5 µg mL-1, these CDs induce significant perturbations on the cellular membrane, resulting in increased membrane permeability due to asymmetric disruption of the bilayer structure. Furthermore, CDs exhibit distinct mechanisms at different concentrations, including prompt insertion into the bilayer at low concentrations (<20 µg mL-1) and a synergistic effect after a threshold time at high concentrations (e.g., 25-200 µg mL-1). Moreover, these CDs possess specific antibacterial properties against Acinetobacter baumannii (with a minimum inhibitory concentration of 50 µg mL-1) while showing minimal hemolytic or cytotoxic effects on mammalian cells. This study provides comprehensive insights into the biophysical aspects of cellular membrane toxicity caused by small weakly negatively charged CDs and contributes to assessing their potential biomedical applications.

CT-guided Percutaneous Microwave Ablation Combined with Local Radiotherapy or Chemotherapy of Malignant Pulmonary Tumors.

BACKGROUND AND OBJECTIVE: The study aimed to investigate the clinical efficacy of CT-guided microwave ablation (MWA) combined with 125I seed implantation or bronchial arterial infusion (BAI) chemotherapy in the treatment of malignant pulmonary tumors. METHODS: A total of 56 patients who underwent MWA, MWA combined with 125I particle implantation, or MWA combined with BAI chemotherapy for advanced lung cancer or metastatic lung cancer from January 2015 to June 2021 in Guangdong Provincial People's Hospital were enrolled. Among them, 21 patients were treated with MWA (MWA), 18 with MWA combined with 125I seed implantation (MWA+125I), and 17 with MWA combined with BAI chemotherapy (MWA+BAI). The short-term outcomes, complications, Eastern Cooperative Oncology Group (ECOG) performance score (Zubrod-ECOG-WHO, ZPS), survival, and factors related to survival were compared between the three groups. RESULTS: The response rate of the MWA group (9.52%) was significantly lower than that of the MWA+125I group (50.00%) and MWA+BAI chemotherapy group (47.06%), and the differences were statistically significant (p < 0.05). The incidence of complications in the MWA, MWA+125I, and MWA+BAI chemotherapy groups was 47.62%, 55.56%, and 52.94%, respectively, with no significant difference (p > 0.05). Three months after the treatment, the ZPS of the MWA+125I and MWA+BAI chemotherapy groups was significantly lower than before treatment and significantly lower than that of the MWA group in the same period; the differences were statistically significant (p < 0.05). The median survival time of the MWA+125I group was 18 (9.983, 26.017) months and that of the MWA+BAI chemotherapy group was 21 (0.465, 41.535) months, both of which were higher than that of the MWA group [11 (6.686, 15.314) months]; the differences were statistically significant (p < 0.05). Cox regression analysis was performed on the factors related to survival and revealed treatment mode as a protective factor [HR = 0.433, 95% CI = (0.191, 0.984), p = 0.046]. Other factors, such as gender, age, and tumor size, did not independently affect survival. CONCLUSION: CT-guided MWA combined with 125I seed implantation and MWA combined with BAI chemotherapy are safe and effective for the treatment of advanced lung cancer and metastatic lung cancer, and can control tumor progression and prolong survival time.

Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity.

INTRODUCTION: Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. AIMS: This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. METHODS: The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. RESULTS: The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. CONCLUSION: These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

Circ-CCT2 Activates Wnt/ß-catenin Signaling to Facilitate Hepatoblastoma Development by Stabilizing PTBP1 mRNA.

BACKGROUND & AIMS: Circ-CCT2 (hsa_circ_0000418) is a novel circular RNA that stems from the CCT2 gene. However, the expression of circ-CCT2 and its roles in hepatoblastoma are unknown. Our study aims to study the circ-CCT2 roles in hepatoblastoma development. METHODS: Hepatoblastoma specimens were collected for examining the expression of circ-CCT2, TAF15, and PTBP1. CCK-8 and colony formation assays were applied for cell proliferation analysis. Migratory and invasive capacities were evaluated through wound healing and Transwell assays. The interaction between circ-CCT2, TAF15, and PTBP1 was validated by fluorescence in situ hybridization, RNA pull-down, and RNA immunoprecipitation. SKL2001 was used as an agonist of the Wnt/ß-catenin pathway. A subcutaneous mouse model of hepatoblastoma was established for examining the function of circ-CCT2 in hepatoblastoma in vivo. RESULTS: Circ-CCT2 was significantly up-regulated in hepatoblastoma. Overexpression of circ-CCT2 activated Wnt/ß-catenin signaling and promoted hepatoblastoma progression, whereas knockdown of circ-CCT2 exerted opposite effects. Moreover, both TAF15 and PTBP1 were up-regulated in hepatoblastoma tissues and cells. TAF15 was positively correlated with the expression of circ-CCT2 and PTBP1 in hepatoblastoma. Furthermore, circ-CCT2 recruited and up-regulated TAF15 protein to stabilize PTBP1 mRNA and trigger Wnt/ß-catenin signaling in hepatoblastoma. Overexpression of TAF15 or PTBP1 reversed knockdown of circ-CCT2-mediated suppression of hepatoblastoma progression. SKL2001-mediated activation of Wnt/ß-catenin signaling reversed the anti-tumor effects of silencing of circ-CCT2, TAF15, or PTBP1. CONCLUSIONS: Circ-CCT2 stabilizes PTBP1 mRNA and activates Wnt/ß-catenin signaling through recruiting and up-regulating TAF15 protein, thus promoting hepatoblastoma progression. Our findings deepen the understanding of hepatoblastoma pathogenesis and suggest potential therapeutic targets.

The chromatin remodeler Ino80 regulates yeast stress tolerance and cell metabolism through modulating nitrogen catabolite repression.

Chromatin remodelers are important in maintaining the dynamic chromatin state in eukaryotic cells, which is essential for epigenetic regulation. Among the remodelers, the multi-subunits complex INO80 plays crucial roles in transcriptional regulation. However, current knowledge of chromatin regulation of the core subunit Ino80 on stress adaptation remains mysterious. Here we revealed that overexpressing the chromatin remodeler Ino80 elevated tolerance to multiple stresses in budding yeast Saccharomyces cerevisiae. Analyses of differential chromatin accessibility and global transcription levels revealed an enrichment of genes involved in NCR (nitrogen catabolite repression) under acetic acid stress. We demonstrated that Ino80 overexpression reduced the histone H3 occupancy in the promoter region of the glutamate dehydrogenase gene GDH2 and the allantoinase gene DAL1. Consistently, the decreased occupancy of nucleosome was revealed in the Ino80-inactivation mutant. Further analyses showed that Ino80 was recruited to the specific DNA locus in the promoter region of GDH2. Consistently, Ino80 overexpression facilitated the utilization of non-preferred nitrogen source to enhance ethanol yield under prolonged acetic acid stress. These results demonstrate that Ino80 plays a crucial role in coordinating carbon and nitrogen metabolism during stress adaptation.

Development and evaluation of polyacrylamide microspheres loaded with phloretin and tantalum for transcatheter arterial embolization.

Transcatheter arterial embolization is an effective treatment for liver cancer. However, the development of novel embolic agents remains a challenge. In this study, we evaluated polyacrylic acid microspheres loaded with phloretin and tantalum as potential embolic agents for liver cancer treatment. Microspheres were synthesised via emulsion polymerisation and characterised in terms of size, shape, and drug-loading efficiency. Nanosized tantalum powder (0 to 15%) was added to the microspheres as an X-ray blocking agent. The maximum drug-loading capacity of the microspheres was approximately 20 mg g-1. The phloretin-loaded microspheres showed a sustained drug release profile in vitro. The microspheres were also evaluated for their in vivo anticancer efficacy in a rabbit VX2 liver tumour model. In conclusion, polyacrylic acid microspheres loaded with phloretin and tantalum have great potential as novel embolic agents for transcatheter arterial embolization for liver cancer treatment.

[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.