Accurate prediction of drug-induced adverse drug reactions(ADRs)is crucial for drug safety evaluation,as it directly impacts public health and safety.While various models have shown promising results in predicting ADRs,their accuracy still needs improvement.Additionally,many existing models often lack interpretability when linking molecular structures to specific ADRs and frequently rely on manually selected molecular fingerprints,which can introduce bias.To address these challenges,we propose ToxBERT,an efficient transformer encoder model that leverages attention and masking mechanisms for simplified molecular input line entry system(SMILES)representations.Our results demonstrate that ToxBERT achieved area under the receiver operating characteristic curve(AUROC)scores of 0.839,0.759,and 0.664 for predicting drug-induced QT prolongation(DIQT),rhabdomyolysis,and liver injury,respectively,outperforming previous studies.Furthermore,ToxBERT can identify drug substructures that are closely associated with specific ADRs.These findings indicate that ToxBERT is not only a valuable tool for understanding the mechanisms underlying specific drug-induced ADRs but also for mitigating potential ADRs in the drug discovery pipeline.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

AIM:To analyze the clinical value of predicting drug resistance in pulmonary tuberculo-sis patients based on improved machine learning models,and to build a visualization system for veri-fication.METHODS:Retrospectively selected 1 025 pulmonary tuberculosis patients hospitalized in Zhuhai Sixth People's Hospital from March 2019 to March 2024 with drug sensitivity test results as the research object.According to the definition of drug-resistant tuberculosis,the patients were divided in-to 631 sensitive groups(drug sensitivity test results showed no drug resistance),271 RR/MDR groups(meeting the definition of rifampicin resistant tu-berculosis or multi drug resistant tuberculosis,but no drug resistance to any kind of fluoroquino-lones),and 123 pre XDR groups(on the basis of multi drug resistant tuberculosis,and at the same time,drug resistance to any kind of fluoroquino-lones).Analyze clinical data based on the improved machine learning model,help build a drug resistant tuberculosis prediction model,synchronously com-plete feature screening,conduct value analysis on the screened features,and build a visual system for verification.RESULTS:Three groups of patients with baseline data comparison shows:Age,Body mass index(BMI),basic treatment of classification,lung diseases,haemoptysis,second-line drug use history,damage to lung,with empty in all statisti-cally significant difference between the three groups(P<0.05);Based on the modified ma-chine learning model,8 variables were screened,which were history of second-line drug use,BMI,treatment classification,destructive lung,underly-ing lung diseases,cavitation,hemoptysis,and age.The modified machine learning model had the high-est prediction accuracy compared with the tradi-tional model,with AUC values of 0.9322(RR/MDR prediction was positive class)and 0.9545(pre-XDR prediction was positive class).CONCLUSION:The application of the improved machine learning mod-el can help predict the occurrence of drug-resistant tuberculosis and assist the clinical formulation of more effective treatment plans.

Objective To investigate the differential expression genes(DEGs)related to angiogenesis in rosacea(RA)by utilizing bioinformatics analysis in order to screen the key genes and verify their mRNA expression levels.Methods The gene microarray dataset GSE65914 was retrieved from the Gene Expression Omnibus(GEO)repository.Analyzed by R programming,the dataset was refined to identify DEGs related to RA,and then cross-referenced with angiogenesis-related genes from the GeneCards database to get a subset specific to RA angiogenesis.The process of identifying key genes was augmented by employing protein-protein interaction(PPI)network analysis and Cytoscape-based computational algorithms.The mRNA expression levels of the aforementioned pivotal genes were detected by real-time fluorescent quantitative reverse transcription PCR(RT-qPCR).Results A total of 947 RA-associated DEGs were identified from GEO dataset,and then 202 genes related to RA angiogenesis were further delineated.PPI network analysis and Cytoscape algorithm finally identified 3 key genes,that is,CXCL8,IL-1B,and STAT1.The results of RT-qPCR showed that the mRNA expression levels of MIP-2,GCP-2,IL-1B and STAT1 in RA lesions were significantly higher than those in normal controls(P<0.05).Conclusion With aid of bioinformatics analysis,our study has screened and validated key genes associated with angiogenesis in RA,namely CXCL8,IL-1B,and STAT1,which providing a theoretical basis for elucidating the potential mechanisms underlying RA-induced angiogenesis and developing targeted therapeutic strategies.

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

Medical record homepage is a core basis for healthcare quality management, medical insurance payment, and public hospital performance evaluation.The completeness and accuracy of its data directly affect the medical quality and economic benefits of hospitals. Since July 2022, a tertiary hospital had built an auxiliary decision-making system for diagnosis omissions based on artificial intelligence technology, which was officially launched in January 2023. The system aimed to improve the quality of data on the first page of medical records and ensure reasonable payment by medical insurance. This system was built on the hospital′s electronic medical records, and integrated natural language processing, medical knowledge graphs and deep learning technologies to create three engines: diagnosis omission recognition, ICD coding and DRG grouping. The diagnosis omission recognition engine identified both explicit and implicit omitted diagnoses by using a context semantic analysis model and a contrastive learning framework for dual judgment. It also interacted with the ICD coding and DRG grouping engines to enhance the accuracy of DRG grouping. Since its launched, the system has achieved remarkable results. A comparative analysis revealed that the rate of missing diagnoses on hospital medical record homepages has decreased from 31.31% during January to September 2022 to 12.34% during the same period in 2023, and the quality control time for a single medical record had been reduced from 20 minutes to 5 minutes. Additionally, a simulation calculation showed that the system-assisted DRG grouping can increase the hospital′s medical insurance surplus. The system could provide reference and guidance for public hospitals in China to improve the quality of the homepage of medical records and better adapt to medical insurance payment reform.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.