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.

Objective To investigate the impact of anticentromere antibody(ACA)on the clinical features and prognosis of patients with primary biliary cholangitis(PBC)by comparing clinical classification,ursodeoxycholic acid(UDCA)response,GLOBE score,and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients.Methods A total of 749 patients who were admitted to Beijing Ditan Hospital,Capital Medical University,from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients.According to their conditions on admission,the two groups were compared in terms of the distribution of clinical types,i.e.,chronic progression-type PBC,portal hypertension-type PBC,and standard jaundice/liver failure-type PBC.There were 261 patients with complete data after 1-year follow-up,among whom there were 53 patients with positive ACA and 208 with negative ACA.A statistical analysis was performed,and propensity score matching was performed based on sex and age at a ratio of 1∶2.The two groups were compared in terms of 1-year UDCA response rate,GLOBE score,and UK-PBC score before and after matching.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results Compared with the ACA-negative group,the ACA-positive group had a significantly higher age(61.28±10.35 years vs 56.74±12.17 years,t=4.164,P<0.001),a significantly higher proportion of female patients(93.9%vs 77.6%,χ2=20.221,P<0.001),a significantly higher proportion of patients with portal hypertension(48.3%vs 27.6%,χ2=23.289,P<0.001),and a significantly lower proportion of patients with jaundice/liver failure(24.5%vs 38.5%,χ2=10.205,P<0.001).After 1-year follow-up,for the 261 PBC patients with complete data,there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group(41.5%vs 41.8%,P>0.05),and there was a significant difference in the proportion of patients with a GLOBE score of>0.3 between the ACA-positive group and the ACA-negative group(92.5%vs 80.3%,χ2=3.935,P=0.047).There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching,and there were no significant differences between the two groups in UDCA response rate,GLOBE score,and UK-PBC score(all P>0.05).Conclusion ACA-positive patients tend to have an older age,with a higher proportion of female patients or patients with portal hypertension,while there is a relatively low proportion of patients with jaundice/liver failure.Positive ACA has no significant impact on UDCA response rate,GLOBE score,and UK-PBC score.

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

OBJECTIVES: To investigate the clinical and immunological features of children with primary immune thrombocytopenia (pITP) or connective tissue disease (CTD) with thrombocytopenia as the initial manifestation at initial diagnosis, and to provide a basis for early differentiation. METHODS: A retrospective study was performed on 236 children with pITP (pITP group) or CTD with thrombocytopenia as the initial manifestation (CTD-TP group) who were admitted from January 2019 to August 2024. Clinical and immunological indicators were compared between the two groups to identify potential influencing factors for early differentiation and their discriminative validity. RESULTS: Compared with the pITP group, the CTD-TP group had a significantly older age of onset and significantly lower leukocyte count, eosinophil count, lymphocyte count, and complement C4 level (P<0.05), as well as significantly higher levels of C-reactive protein, IgE, and IgM (P<0.05). The logistic regression analysis showed that age, IgE, IgM, total B cells, and complement C4 were predictive factors for early differentiation between pITP and CTD-TP (P<0.05). The receiver operating characteristic curve analysis showed that a combination of these five factors had a good discriminative validity, with an area under the curve of 0.944. The correlation analysis showed a negative correlation between IgG and platelet count in the pITP group (r_s=-0.363, P<0.05) and a positive correlation between NK cells and platelet count in the CTD-TP group (r_s=0.713, P<0.05). CONCLUSIONS There is heterogeneity in the clinical and immunological indicators between children with pITP and CTD-TP at initial diagnosis, and these research findings can help with the early differentiation between the two diseases.
Purpura, Thrombocytopenic, Idiopathic/immunology* ; Diagnosis, Differential ; Connective Tissue Diseases/immunology* ; Retrospective Studies ; Early Diagnosis ; Age of Onset ; Leukocyte Count ; Complement C4/immunology* ; C-Reactive Protein/immunology* ; Immunoglobulin E/immunology* ; Immunoglobulin M/immunology* ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; Biomarkers/blood*

Objective:To investigate the dietary iodine intake levels of residents and the dietary iodine contribution rates in Hainan Province.Methods:Using cluster random sampling method, common foods sold in 21 counties (cities, districts) markets in Hainan Province in 2023 were collected to determine iodine content. Each county (city, district) was divided into five sampling areas by east, west, south, north, and center, with one township (street) selected from each area, and 20 permanent residents over 18 years old (non same household, half male and half female) and 20 pregnant women were selected from each township (street). The "Iodine-Specific Food Frequency Questionnaire (I-FFQ)" was used to investigate the daily dietary intake of adults and pregnant woman. The average daily salt intake of the survey subjects was measured by the 3-day weighing method, and the dietary iodine intake and the dietary iodine contribution rates were calculated.Results:A total of 632 food samples were collected, and the iodine content of seaweed was relatively high (4 424.76 μg/100 g); the iodine content of seasoning was relatively low (2.41 μg/100 g). A total of 4 227 individuals in Hainan Province were surveyed for dietary iodine intake. The median dietary iodine intake level of residents was 211.6 μg/d, with the medians dietary iodine intake level of adults and pregnant women being 204.5 and 218.4 μg/d ( n = 2 120, 2 107), respectively. There was a statistically significant differences between different populations ( Z = - 8.64, P < 0.001). The medians dietary iodine intake level in the western coastal areas, central mountainous regions, and eastern coastal areas were 210.0, 207.3 and 211.6 μg/d ( n = 1 205, 1 203, 1 819), respectively, with statistically significant differences between different regions ( H = 15.33, P < 0.001). The contribution rate of dietary iodine from iodized salt was the most (59.4%), followed by kelp (8.1%). Conclusions:Under the condition of consuming iodized salt, the dietary iodine intake of adults in Hainan Province meets the recommended dietary iodine intake ( > 120 μg/d), but the dietary iodine intake of pregnant women is insufficient ( < 230 μg/d). Iodized salt is the main source of dietary iodine for residents in Hainan Province.

Objective:To describe epidemiological characteristics and their influencing factors of diabetes and pre-diabetes among adult residents in Hainan Province and provide a theoretical basis to develop epidemic prevention and control strategies for diabetes.Methods:This study used a two-stage unequal proportion cluster sampling method, and 32 857 subjects (≥18 years old) were collected from 24 cities/counties/districts in Hainan Province. All the subjects were investigated with questionnaires, physical examination, and laboratory tests from January to June 2023. The χ2 and Mantel-Haenszel trend χ2 tests were used to analyze the data. Multivariate logistic regression was used to analyze the factors influencing diabetes and pre-diabetes. SPSS 23.0 software was used to analyze the data. Results:The crude prevalence of diabetes and pre-diabetes in adult residents of Hainan Province were 18.1% and 22.8%, while the weighted rates were 13.7% and 20.7%, respectively. The results of multivariate logistic regression analysis showed that: aging (30-39 years old: OR=2.65, 95% CI: 2.06-3.41; 40-49 years old: OR=5.64, 95% CI: 4.40-7.24; 50- 59 years old: OR=9.88, 95% CI: 7.71-12.67; 60-69 years old: OR=18.34, 95% CI: 14.28-23.55; 70-79 years old: OR=21.30, 95% CI: 16.41-27.65; 80 years old and above: OR=24.13, 95% CI: 17.94-32.46), nationality (Li minority group: OR=1.50, 95% CI: 1.38-1.63; other ethnic groups: OR=1.53, 95% CI: 1.20-1.94), urban ( OR=1.12, 95% CI: 1.04-1.21), central obesity ( OR=2.14, 95% CI: 2.01-2.29), higher frequency of alcohol consumption (5-7 day/week: OR=1.24, 95% CI: 1.11-1.38), physical inactivity ( OR=1.09, 95% CI: 1.02-1.17) were risk factors for diabetes, while aging (30-39 years old: OR=1.53, 95% CI: 1.31-1.79; 40-49 years old: OR=2.36, 95% CI: 2.01-2.76; 50-59 years old: OR=3.03, 95% CI: 2.58-3.55; 60-69 years old: OR=4.22, 95% CI: 3.58-4.97; 70-79 years old: OR=5.05, 95% CI: 4.23-6.04; 80 years old and above: OR=6.08, 95% CI: 4.86-7.61), nationality: (Li minority group: OR=1.18, 95% CI: 1.10-1.28; other ethnic groups: OR=1.40, 95% CI: 1.14-1.71), urban ( OR=1.12, 95% CI: 1.04-1.19), central obesity ( OR=1.72, 95% CI: 1.62-1.83), higher frequency of alcohol consumption (1-4 day/week: OR=1.12, 95% CI: 1.01-1.23; 5-7 day/week: OR=1.35, 95% CI: 1.22-1.49) were risk factors for pre-diabetes. Conclusions:The epidemic situation of diabetes and pre-diabetes among adult residents in Hainan Province was not optimistic. In order to control the development of abnormal blood glucose, measures and targeted health education should be carried out to strengthen the screening, treatment, and management of people with abnormal blood glucose among different populations.

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.

Objective:To systematically investigate the association and regulatory mechanism between genetic variants in the binding region of pancreatic and duodenal homeobox 1 (PDX1) and pancreatic cancer susceptibility in the Chinese population.Methods:Chromatin immunoprecipitation sequencing (ChIP-seq) was performed using the human pancreatic cancer cell line BxPC-3 to identify and annotate genetic variants within the PDX1 binding region. A two-center case-control study was conducted, and logistic regression models were employed to analyze the association between PDX1-related variants and pancreatic cancer susceptibility. Functional experiments were performed to elucidate the molecular mechanisms of these genetic variants.Results:ChIP-seq analysis identified 1 608 PDX1 binding regions. SNPs within these regions were significantly enriched in susceptible areas of pancreatic cancer ( P<0.001). The common variant rs154659, located within the most significant PDX1 binding peak, was further investigated. The multivariate logistic regression model showed that compared with individuals with TT genotype, individuals with CC genotype had a reduced risk of pancreatic cancer by 29.2% ( OR=0.708, 95% CI: 0.589-0.850). Functional studies demonstrated that the rs154659[C] allele displayed higher relative luciferase activity than the rs154659[T] allele. Knockdown of PDX1 significantly attenuated the relative luciferase differences between the two alleles. Conclusion:Genetic variants in the PDX1 binding region are associated with pancreatic cancer risk. The rs154659 modulates pancreatic cancer susceptibility by specifically altering PDX1 binding activity.

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.