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.

Gastric cancer remains a highly prevalent malignancy worldwide, with surgical resection currently constituting the cornerstone of treatment aimed at improving long-term patient survival. Owing to their notable advantages, including reduced surgical trauma and accelerated postoperative recovery, minimally invasive procedures are progressively supplanting conventional open surgery and have become the mainstream approach in gastric cancer management. Concurrently, the rapid advancement of artificial intelligence (AI) technologies has enabled real-time intraoperative monitoring of surgical scenes, thereby furnishing novel technical support for adjunctive decision-making, surgical navigation, and skill assessment during gastrectomy. This article provides a systematic review of the current status of AI applications in minimally invasive gastric cancer surgery, with a particular focus on research progress pertaining to instrument recognition, surgical phase identification, delineation of normal anatomical structures, detection of metastatic foci, and early warning of intraoperative adverse events. Furthermore, we discuss the potential value of AI in enhancing surgical efficiency, ensuring patient safety, and optimizing surgical education. On this basis, we further analyze the principal challenges and inherent risks confronting current AI systems, with the aim of informing future technological innovation and facilitating clinical translation.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.

Asthe standard for drafting standards,the Rules for Compiling National Standards for Pharmaceutical Excipients was first issued in the 2020 edition and then revised and re-issued in 2025.It has become an important technical specification for the pharmaceutical excipients standards in the Chinese Pharmacopoeia and for the phar-maceutical excipients standards formulated by pharmaceutical companies for associated review and approval.This article focuses on introducing the working background,main framework and main characteristics of the Rules for Compiling National Standards for Pharmaceutical Excipients,aiming to help the drafters,reviewers and implement-ers of pharmaceutical excipients standards better understand and master them,so as to further improve the standard-ization of writing pharmaceutical excipients standards and enhance the level of standards formulation and revision of pharmaceutical excipients.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*