Cigarette smoke is recognized as a major trigger for individuals with chronic obstructive pulmonary disease (COPD), leading to an amplified inflammatory response. The onset and progression of COPD are affected by multiple environmental and genetic risk factors, such as inflammatory mechanisms, oxidative stress, and an imbalance between proteinase and antiprotease. As a result, conventional drug therapies often have limited effectiveness. This study aimed to investigate the anti-inflammatory effect of sodium butyrate (SB) in COPD and explore its molecular mechanism, thereby deepening our understanding of the potential application of SB in the treatment of COPD. In our study, we observed an increase in the mRNA and protein expressions of inflammatory factors interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Matrix metallopeptidase 9 (MMP9) and MMP12 in both NR8383 cell and rat models of COPD. However, these expressions were significantly reduced after SB treatment. Meanwhile, SB treatment effectively decreased the phosphorylation levels of nuclear transcription factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear translocation of these proteins in the COPD cells, leading to a reduction in the expression of various inflammatory cytokines. Additionally, SB also inhibited the expression level of the Nod-like receptor pyrin domain 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 in the cigeratte smoke extract (CSE)-stimulated cells. Our results showed that CSE down-regulated the mRNA levels of G-protein-coupled receptor 43 (GPR43) and GPR109A, while SB only up-regulated the expression of GPR43 and had no effect on GPR109A. Moreover, additional analysis demonstrated that the knockdown of GPR43 diminishes the anti-inflammatory effects of SB. It is evident that siRNA-mediated knockdown of GPR43 prevented the reduction in mRNA expression of IL-1β, IL-6, TNF-α, MMP9, and MMP12, as well as the expression of phosphorylated proteins NF-κB p65, JNK, and p38 MAPKs with SB treatment. These findings revealed a SB/GPR43 mediated pathway essential for attenuating pulmonary inflammatory responses in COPD, which may offer potential new treatments for COPD.

Purpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023. Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms. Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region. Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.

Azole resistance in Aspergillus fumigatus poses a significant clinical challenge globally. In this study, we analyzed 307 clinical A. fumigatus isolates from General Hospital of Ningxia Medical University in China, collected between July 2023 and July 2024, to explore their susceptibility profiles, genotypic characteristics and biological traits. The overall frequency of azole resistance among clinical isolates in Ningxia province was found to be 1.20% (7 azole-resistant A. fumigatus, designated AF1-AF7), each exhibiting distinct phenotypes in terms of azole resistance, spore viability, and resilience to environmental stress. Among these strains, the cyp51A mutations predominantly included TR43/L98H, while the hmg1 mutations were primarily S212P/Y564H. Additionally, novel mutations were discovered in cyp51B, specifically the t-215c point mutation and a base deletion (gatgccta) in the - 213 to - 206 region. The AF3 strain demonstrated the highest spore activity and anti-SDS efficacy. In contrast, the AF1 and AF2 strains were resistant to three azoles and also exhibited resistance to Menadione, similar to AF7. Notably, six out of the seven strains displayed resistance to NaCl and KCl, indicating a strong tolerance to saline conditions. These findings suggest that azole-resistant strains possess varying degrees of resistance to environmental stressors, implying that they may adapt to their surroundings through different evolutionary pathways, which could complicate clinical treatment strategies. Effective surveillance and control strategies are essential to control the widespread prevalence of azole-resistant A. fumigatus and to reduce the risk of infection in patients.

The global issue of Helicobacter pylori (H. pylori) resistance has become increasingly severe, with biofilm formation identified as a significant contributor to drug resistance and subsequent treatment failures. This study investigated 78 strains of H. pylori in the Ningxia province of China over a two-year period, focusing on infection rates, drug resistance, biofilm formation, and genetic characteristics. The results indicated that 56 strains (71.8%) exhibited resistance, and 48 patients (61.5%) were diagnosed with atrophic gastritis. Notably, metronidazole resistance was the most prevalent, accounting for 65.3%, and multidrug-resistant strains were also identified. Further investigation revealed that high biofilm-forming H. pylori demonstrated a higher proportion of resistance to metronidazole, clarithromycin, and levofloxacin compared to low biofilm-forming H. pylori. Next-generation sequencing data demonstrated low homology among the strains, suggesting that this genetic diversity may drive the strains to evolve along distinct pathways, ultimately resulting in the emergence of more complex drug-resistant isolates within the studied population, despite the limited data size.

The global prevalence of ST11 hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) isolates has been increasingly documented, yet genomic characterization of this clone remains insufficiently explored. Here, we report a clinical ST11-KL25 hv-CRKP strain (KP156) that exhibited resistance to multiple antibiotics and demonstrated hypervirulence in a mouse infection model. Whole-genome sequencing revealed that KP156 harbored one virulence plasmid (pKP156-Vir) and two resistance plasmids (pKP156-KPC and pKP156-tetA). The pKP156-Vir contains several virulence factors, including rmpA2 and iucABCD, which are critical contributors to its hypervirulence. The bla_KPC-2 and bla_CTX-M-65 genes, located within the Tn6296 transposon of pKP156-KPC, along with a multidrug-resistant (MDR) region containing multiple transposons and conjugative elements in pKP156-tetA, are associated with the transfer of resistance genes. Phylogenetic analysis indicates that KP156 shares high homology with other ST11 hv-CRKPs, suggesting potential transmission of this clone. Our study informs the development of genomic surveillance and control strategies for this strain.

Objectives: This study aimed to retrospectively investigate the epidemiology and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from neonatal intensive care units (NICU) between 2017 and 2021. Methods: The antibacterial susceptibility of all strains was assessed using the VITEK 2 compact system. The presence of antibiotic resistance, virulence genes, sequence types (STs), capsular (K) types, and the wzi genes was determined through polymerase chain reaction (PCR). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme XbaI. Additionally, the virulence potential of peg344-positive strains was evaluated using the string test and mouse intraperitoneal infection models. Whole-genome sequencing was conducted on the DNB system and PacBio platforms. Results: A total of 46 CRKP isolates were collected during the study period. Out of these, 93.47% (43/46) were identified as CRKP strains belonging to the ST76-K10 type carrying bla_NDM-5. It was observed that CRKP infection resulted in more severe clinical symptoms compared to CRKP colonization. Among the CRKP strains, a hypervirulent CRKP strain called KP-63, belonging to the ST23 type, was identified. This strain exhibited high mortality in the mouse infection model and was found to possess virulence genes. Genomic alignment analysis revealed a significant similarity between the virulence plasmid from KP-63 strain (pKP-63) and pK2044 from the hypervirulent K. pneumoniae strain NTUH-2044. Conclusions: There has been a potential dissemination of ST76-K10 type CRKP carrying bla_NDM-5 in the NICU at Ningxia Hospital. Neonatal CRKP infection has been found to cause more severe clinical symptoms than colonization. Furthermore, we have discovered a CR-hvKP strain of ST23 with serotype K1, which exhibits a significant resemblance in its virulent plasmid to pK2044. Therefore, it is crucial to enforce effective measures to restrict the spread and hinder the evolution of CRKP within the hospital.