Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Processed electroencephalogram (EEG) indices, such as the Bispectral Index, have markedly influenced anesthesia practice as they translate brain activity into simple numerical indices. Nevertheless, as the manufacturing algorithms are not disclosed, the underlying neurophysiology remains obscured. Additionally, these indices are often affected by electromyographic contamination, pharmacological variability, and patient-specific EEG heterogeneity. In contrast, an EEG spectrogram, or density spectral array, preserves the frequency- and time-resolved structures of cortical oscillations. This information is presented in a form that is both physiologically meaningful and clinically interpretable. In this review, we trace the evolution of anesthesia from an index-based to a spectrogram-guided approach, and summarize the clinical rationale for adopting the latter. Key applications of this approach include the use of frontal alpha power as a biomarker of cortical stability and postoperative brain health, the identification of nociceptive arousal through alpha dropout and beta or delta arousal patterns, and individualized titration of multimodal or age-specific anesthetic management. Although current devices lack standardized quantitative alpha metrics and have limited sensitivity for low-frequency brain wave components, structured EEG education programs have proven to be effective in terms of fostering spectrogram literacy among anesthesiologists. By combining neurophysiological precision with bedside practicality, the EEG spectrogram represents a pivotal advance toward individualized, mechanism-based, and brain-protective anesthesia, transforming anesthetic monitoring from mere algorithmic abstraction to cortical insight.

With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

AIM To evaluate the quality of benchmark sample of Zexie Decoction.METHODS HPLC fingerprints were established,after which the content determination of epoxy alisma ene,23-acetyl alisol B,23-acetyl alisol C,alisol A,alisol B,atractylenolide Ⅰ,atractylenolide Ⅱ and atractylenolide Ⅲ was performed,and the transfer rate and paste yield were calculated.RESULTS There were 20 common peaks in the fingerprints for 15 batches of benchmark samples with the similarities of more than 0.95.The average contents of various effective constituents were 180.86 μg/g for alisol B 23-acetate,18.65 μg/g for alisol C 23-acetate,34.74 μg/g for alismoxide,17.65 μg/g for alisol A,238.19 μg/g for alisol B,2.85 μg/g for atractylenolide Ⅰ,6.38 μg/g for atractylenolide Ⅱ,and 15.42 μg/g for atractylenolide Ⅲ,respectively.In the decoction piece-benchmark sample,alisol B 23-acetate,alisol C 23-acetate,atractylenolide Ⅰ,atractylenolide Ⅱ and atractylenolide Ⅲ demonstrated the average transfer rates of 12.09％,16.45％,3.93％,12.17％and 34.37％respectively.The paste yields in various batches of benchmark samples were 15.2％-20.2％.CONCLUSION HPLC fingerprints combined with content determination can be used for the quality control of benchmark sample of Zexie Decoction,thus provides a reference for the development of its compound preparations.

Objective:To explore the value of 18F-FDG PET brain glucose metabolism imaging in the subtype differential diagnosis and prognosis evaluation of autoimmune encephalitis (AE). Methods:A retrospective analysis was conducted on PET/CT brain glucose metabolism imaging data from 58 patients with AE (from August 2020 to June 2023, Xuanwu Hospital, Capital Medical University; 31 males, 27 females; age (47.4±16.9) years). Patients were divided into 4 groups: anti-leucine-rich glioma-inactivated protein 1(LGI1) antibody-related encephalitis group, anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis group, anti-γ-amino butyric acid type B receptor (GABA BR) antibody-related encephalitis group, and other types of AE group. In addition, 20 cases were included in control group (6 males and 14 females, age (58.8±7.5) years). Visual assessment was performed to evaluate changes in brain glucose metabolism among patients with different subtypes of AE, and abnormal glucose metabolism brain regions were compared by independent-sample t test between different groups. Spearman rank correlation analysis was conducted between SUV ratio (SUVR) of abnormal brain regions and modified Rankin Scale (mRS) scores at six months later. Results:Among 58 patients, 21 were diagnosed with anti-LGI1 antibody-related encephalitis, 18 were diagnosed with anti-NMDAR encephalitis, 7 were diagnosed with anti-GABA BR antibody-related encephalitis, and 12 were diagnosed with other subtypes of AE. Compared with anti-NMDAR encephalitis group: patients with anti-LGI1 antibody-related encephalitis showed increased glucose metabolism in the right occipital lobe and bilateral hippocampi, and decreased glucose metabolism in the right frontal lobe, right precentral gyrus, and bilateral superior marginal gyrus ( t values: from -5.13 to 4.89, all P<0.001); patients with anti-GABA BR antibody-related encephalitis exhibited increased glucose metabolism in the bilateral hippocampi and right fusiform gyrus, and decreased glucose metabolism in the left middle frontal gyrus ( t values: from -3.82 to 3.91, all P<0.001). Anti-NMDAR encephalitis was characterized by decreased metabolism in the bilateral parietal lobes, occipital lobes, local frontal-temporal lobes, and bilateral thalami, as well as increased metabolism in the limbic lobe and local frontal-temporal-parietal lobes ( t values: from -8.30 to 7.30, all P<0.001), and the SUVR of the right occipital lobe was negatively correlated with mRS score at six months later ( rs=-0.64, P=0.014). Other subtypes of AE showed decreased glucose metabolism in different cerebral lobes. Conclusion:18F-FDG PET/CT can evaluate brain glucose metabolism in different subtypes of AE diseases and prognosis.

Objective:To understand the incidence and epidemiological characteristics of enteritis due to norovirus infection in Guizhou Province from 2016 to 2023, and provide reference for the prevention and control of enteritis caused by norovirus.Methods:The data were from National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. To collect the data of other infectious diarrhea cards in Guizhou from 2016 to 2023, which were annotated as enteritis due to norovirus and food-borne disease surveillance sentinel report in Guizhou, which were positive for norovirus detection. The data of cluster/outbreaks were from the Public Health Emergency Event Surveillance System and the field investigation reports of CDC at all levels. Descriptive epidemiological method was used to describe the characteristics of its three-dimension distribution, epidemic situation and pathogen spectrum. R 4.2.2 software was used for statistical analysis.Results:A total of 2 340 cases of enteritis due to norovirus were reported in Guizhou Province during this period, with an average annual reported incidence of 0.79/100 000, and the incidence showed an upward trend (trend χ2=1 723.80, P<0.001). The high incidence season is from October to March (winter and spring). The male to female ratio of the cases was 1.39∶1 (1 362∶978). A total 1 382 cases occurred in age group under 5 years old (59.06%) and 1 249 cases occurred in children living scatteredly (53.38%). The average annual reported incidence in 6 prefectures (muniipality)(1.15/100 000 in Qiandongnan Miao and Dong Autonomous Prefecture, 1.08/100 000 in Guiyang, 1.07/100 000 in Liupanshui, 1.06/100 000 in Qianxinan Buyi and Miao Autonomous Prefecture, 0.91/100 000 in Qiannan Buyi and Miao Autonomous Prefecture and 0.89/100 000 in Tongren) in Guizhou Province was higher than provincial level, and the affected areas gradually expanded from southeastern counties (districts) to western and northern counties (districts). The average annual reported incidence rate was higher in urban area (1.12/100 000) than in rural area (0.39/100 000). A total of 31 cluster/outbreaks of enteritis due to norovirus were reported, in which 83.87% (26/31) occurred in child care settings, primary and secondary schools, in which 74.19% (23/31) were caused by human-to-human transmission. In the 2 340 cases, 2 147 were laboratory diagnosed (91.75%), and 193 were clinically diagnosed (8.25%). In the laboratory diagnosed cases, 2 026 (94.36%) were caused by single norovirus infection and 121 (5.64 %) were caused by mixed infection. Conclusions:On the whole, the incidence of enteritis due to norovirus in Guizhou Province was on the rise from 2016 to 2023, and winter and spring were the high incidence seasons. Effective prevention and control measures should be taken for key populations, key regions and key places, and multi-channel and multi-pathogen surveillance and health education should be strengthened.

Objective To analyze the current status and hotspots of domestic research on traditional Chinese medicine(TCM)in treating chronic refractory wounds(CRW)over the past 10 years using bibliometric and visualized analysis methods.Methods Articles about TCM therapy for CRW issued by the core periodicals in recent 10 years were retrieved from CNKI,Wanfang and VIP databases.The parameters of annual issued papers,authors,institutions and keywords of the articles were counted with the bibliometric methods.And then the statistical results were presented as visualized graphs by using VOSviewer and CiteSpace software.Results A total of 404 articles were included in the study,and 313 institutions and 1 340 scholars participated in the research on the treatment of CRW with TCM.However,there was limited collaboration between the authors and institutions.Research hotspots mainly focused on the efficacy of TCM external therapies for diabetic foot and pressure ulcers,and discussions on syndrome differentiation,treatment principles and methods about internal treatment by various medical experts.The development and application of Chinese patent medicines,exploration of TCM medication patterns,and the evidence-based medical research on TCM are future research trends in the treatment of CRW with TCM.Conclusion Research on TCM treatment of CRW has attracted significant attention in recent years,but academic barriers exist between the authors and institutions.In the future,it is necessary to promote multicenter research collaboration,strengthen the exploration of experiences in acupoint selection,and conduct higher-level research,thus to provide more compelling evidence and enhance the efficacy of TCM in treating CRW.

Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.