Research Medical Center

BACKGROUND:Colorectal cancer (CRC) encompasses various cancers located in the rectosigmoid junction, rectum, and anus, as well as parts of the colon. Globally, CRC is the second leading cause of cancer-related mortality and the third most prevalent malignancy. The KRAS oncogene was found to be mutated in 30 to 50% of CRC cases, leading to dysregulated cellular functions. Furthermore, the connection between KRAS and P53 gene mutations and the incidence of both colorectal and breast cancer remains an area of interest. METHODS:This comprehensive narrative review was carried out by mining data from recognized databases, such as PubMed, Google Scholar, and ResearchGate. The purpose was to extensively explore and understand the association between the KRAS and P53 gene mutations and the prevalence of colorectal and breast cancers. RESULTS:The mutation in the KRAS oncogene has been identified as a key player in cellular signaling pathways, including MAPK, PI3K, and PLD. Despite extensive research, gene therapies targeting these mutations have seen limited success, especially in codons 12, 13, 61, and 143. CONCLUSION:Mutations in the KRAS and P53 genes, along with aberrant MDM2 expression, play pivotal roles in the onset and progression of colorectal cancer by disrupting key cellular signaling pathways, such as MAPK, PI3K, and PLD. Despite advancements in understanding these mechanisms, current gene therapy approaches have shown limited success, particularly in targeting KRAS codon mutations. This underscores the urgent need for innovative therapeutic strategies and further research to develop effective treatments for colorectal cancer and its potential links to other malignancies, such as breast cancer.

Introduction:Obesity is a well-established risk factor for asthma pathogenesis. However, the underlying mechanisms remain incompletely understood, and effective therapeutic interventions are currently lacking, making asthma management in obese individuals particularly challenging. Asthma is characterized by chronic airway inflammation, eosinophilic infiltration, and airway hyperresponsiveness (AHR). In this study, we investigated the novel role of fibroblast growth factor 21 (FGF21), a stress-inducible hepatokine with pleiotropic metabolic regulatory functions, in obesity-associated AHR using a diet-induced obesity mouse model (n = 10). Material and Methods:Serum samples were collected from obese and lean asthma patients, along with relevant clinical indicators, including body mass index (BMI), forced expiratory volume in 1 second (FEV1%), and the FEV1/forced vital capacity (FVC) ratio, to facilitate the investigation. Moreover, diet-induced obese mice with innate AHR (male, n = 10) were employed to clarify the effects of FGF21 and FGF21-neutralizing antibody on obesity induced AHR. In vitro, LAD2 human mast cells and P815 murine mast cells activated by compound 48/80 were used to elucidate the underlying mechanisms. Results:Our findings demonstrate that serum FGF21 levels exhibit reportedly elevated in participants with obesity and are associated with impaired pulmonary function. In diet-induced obese (DIO) mice, FGF21 levels were increased in both serum and bronchoalveolar lavage fluid (BALF). In vivo investigations demonstrate that administration of recombinant FGF21 exacerbated AHR in DIO mice, whereas FGF21-neutralizing antibody treatment ameliorated obesity-induced AHR and suppressed mast cell infiltration. Mechanistically, FGF21 was found to potentiate mast cell activation through cholesterol biosynthesis modulation. Crucially, pharmacological inhibition of FGFR1 abrogated FGF21-induced mast cell hyperactivity and cholesterol synthesis, indicating FGFR1-dependent signaling in this process. Conclusion:These findings may represent the FGF21/FGFR1 axis as a potential therapeutic target for obesity-related AHR and asthma.

Background:Staphylococcus argenteus, a member of the Staphylococcus aureus complex, has increasingly been recognized as a human pathogen but is frequently misidentified as S. aureus in routine clinical laboratories. Reports of prosthetic joint infection (PJI) caused by this species remain rare. Methods:We describe a case of delayed-onset PJI in a 71-year-old woman following total knee arthroplasty. Repeated conventional cultures were negative after empirical vancomycin therapy. Metagenomic next-generation sequencing (mNGS) of wound exudate detected S. argenteus, which guided extended culture and subsequent isolation of low-abundance colonies. Species identification was confirmed by whole-genome sequencing (WGS), multilocus sequence typing (MLST), and reinterpretation of MALDI-TOF MS results. Antimicrobial susceptibility testing (AST) was performed and compared with WGS-based resistance prediction. Phylogenetic analysis was conducted using 452 publicly available S. argenteus genomes. Aim:This study aimed to describe the clinical diagnosis, microbiological identification, and genomic characterization of a Staphylococcus argenteus strain causing prosthetic joint infection. Results:The isolate was identified as sequence type ST2250 and lacked the staphyloxanthin operon, consistent with the non-pigmented phenotype. WGS and phenotypic AST showed 100% concordance across 11 clinically relevant antibiotics. Phylogenomic analysis revealed that the strain clustered closely with Southeast Asian lineages. Following targeted therapy with intravenous vancomycin and surgical wound management, the patient showed rapid clinical improvement with resolution of local inflammation and complete wound healing. Conclusion:This is the first confirmed case of S. argenteus PJI in Suzhou, China. The case highlights the diagnostic value of mNGS in culture-negative PJI, the importance of molecular tools for correctly differentiating S. argenteus from S. aureus, and the potential of WGS to support resistance prediction for rare staphylococcal pathogens.

OBJECTIVE: To analyze the clinical characteristics, diagnostic features, treatment strategies, and prognosis of Bickerstaff brainstem encephalitis (BBE), providing insights into its diagnosis and management. METHODS: A retrospective analysis was conducted on 13 BBE cases treated at a single center from January 2021 to December 2024. Clinical manifestations, diagnostic criteria, treatment regimens, and outcomes were reviewed and summarized of the 13 BBE cases. A comprehensive literature review was also conducted to fully understand the progress of the current study. RESULTS: All patients presented with acute onset, with 6 (46%) having a history of preceding infections, predominantly upper respiratory tract infections (5,38%). Diplopia (5,38%) was the most common initial symptom, while ataxia (13,100%) and ophthalmoplegia (10,76%) were the core features. Anti-GQ1b antibodies were positive in 5 patients (38%), and MRI abnormalities in the brainstem were observed in 2 patients (15%). Combination therapy with intravenous immunoglobulin (IVIg) and steroids was administered to 8 patients (62%), while monotherapy was used in the remainder. At discharge, 1 patient (7%) achieved complete symptom resolution, 7 (54%) showed improvement, and 3 (23%) experienced symptom aggravation. No fatalities were reported, but residual limb weakness persisted in some cases. CONCLUSION: BBE is clinically heterogeneous, often overlapping with GBS and MFS. Diagnosis relies on clinical findings, anti-GQ1b antibody testing, and neuroimaging. Immunotherapy, especially IVIg combined with steroids, is effective in most cases. However, rapid progression and limb weakness at onset may predict poor outcomes, highlighting the need for early intervention and further research to improve the diagnosis and treatment strategies.

Xiaoxi Zhu,1,* Gong Zhang,1,* Lin Li,2,* Puguang Yu,1,* Peng Su,3 Hongyuan Liang,4 Dan Dong,5 Dongyan Liu,6 Kefeng Wang11Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 2Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 3Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 4Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 5College of Basic Medical Science, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China; 6Department of Gastroenterology and Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kefeng Wang, Department of Urology, Shengjing Hospital of China Medical University, #36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People’s Republic of China, Tel +86-18940254849, Email wang.kefeng@hotmail.com Dongyan Liu, Department of Gastroenterology and Medical Research Center, Shengjing Hospital of China Medical University, #7 Mulan Road, Xihu District, Shenyang, Liaoning, 110004, People’s Republic of China, Tel +86-18940259005, Email liudy19701010@sina.comAbstract: Gene silencing by RNA interference (RNAi) has emerged as a promising strategy for cancer therapy. Small interfering RNA (siRNA), a class of small regulatory RNAs that recognize and degrade complementary target messenger RNAs (mRNAs) in a sequence-specific manner at the post-transcriptional level, plays a critical role in regulating gene expression. However, the in vivo delivery of siRNA remains a formidable challenge due to its poor physiological stability, susceptibility to enzymatic degradation, inability to efficiently cross cellular membranes, non-specific off-target effects, and immunostimulation. Overcoming these barriers and enhancing the gene silencing efficiency of siRNA in target cells is essential for the clinical translation of RNAi technology. In recent years, tumor microenvironment (TME)-responsive nanocarriers have attracted considerable attention as a strategy to improve siRNA stability, enhance its enrichment and penetration at tumor sites, facilitate cellular uptake, and promote efficient gene silencing. This review comprehensively summarized the design principles and functional characteristics of TME-responsive siRNA delivery nanocarriers, with a focus on five major stimuli: pH, hypoxia, enzymes, glutathione (GSH), and reactive oxygen species (ROS). We critically analyze the advantages and limitations of existing nanocarrier systems, provide comparative insights through summary tables, and discuss future directions including multi-stimuli-responsive systems, combination therapies, and clinical translation challenges. This review aims to provide a systematic framework for understanding and advancing TME-responsive siRNA nanocarriers for tumor therapy.Keywords: tumor microenvironment, siRNA delivery, nanocarrier, RNA interference, cancer therapy, combination therapy, clinical translation