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 compare the consistency between bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) in measuring body composition among Tibetan children and adolescents and to explore the applicability of BIA in plateau region, so as to provide scientific and convenient body composition measurement support among children and adolescents. Methods: From May to June, 2022, a total of 344 Tibetan children and adolescents aged 6-17 years were selected from Golmud Municipal National Middle School and Changjiangyuan Nationality Primary School in Qinghai Province by cluster sampling method, and their fat mass, fat mass percentage and lean mass were measured by DXA and BIA. The consistency and correlation between the two methods were assessed by using the Wilcoxon rank-sum test, Spearman correlation analysis, intraclass correlation coefficient (ICC), and Bland-Altman analysis. Results: DXA measured fat mass and fat mass percentage were significantly higher than those obtained by BIA (6-12 years old: Z =9.91, 11.28; 13-17 years old: Z =9.02, 10.21), while lean mass and lean mass percentage were significantly lower than BIA results (6-12 years old: Z =-11.60, -11.30; 13-17 years old: Z =-10.77, -10.36) (all P < 0.05 ). The two methods showed strong correlations in fat mass and lean mass (all r >0.80, all ICC >0.90), but exhibited poor agreement in fat mass percentage and lean mass percentage (6-12 years old: Lin s CCC =0.64, 0.41; 13-17 years old: Lin s CCC = 0.79 , 0.35). Bland-Altman analysis showed that the difference between the two methods was negatively correlated with the average value in FM%(6-12 years old: r =-0.75, 13-17 years old: r =-0.79, both P <0.01). Conclusion BIA and DXA show high consistency in measuring body fat mass and lean body mass in Tibetan children and adolescents, although some bias is still present in certain individuals.

OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Introduction: Cranial radiotherapy is an established treatment for intracranial germinoma but may lead to late cerebrovascular complications including radiation-induced vasculopathy, cavernoma formation, and premature intracranial atherosclerosis. These complications may manifest many years after treatment and represent an important cause of stroke in young adult survivors of brain tumors. Case: We report a 39-year-old male with a history of suprasellar germinoma treated with transsphenoidal surgery followed by craniospinal radiotherapy in 2006. He subsequently developed panhypopituitarism requiring lifelong hormone replacement therapy. In October 2024, he experienced a cerebrovascular accident resulting in mild residual right-sided weakness. Brain magnetic resonance imaging demonstrated multifocal old infarcts, small vessel disease (Fazekas grade 2), and multiple susceptibility artifacts suggestive of radiation-induced cavernomas.In March 2026, he presented with new onset right-sided weakness and facial asymmetry. Initial neurological examination revealed right-sided motor power of 4/5. Computed tomography of the brain showed no acute intracranial hemorrhage but confirmed multiple old infarcts and small vessel ischemic changes. Computed tomography angiography revealed intracranial atherosclerotic disease with 25–50% stenosis of the cavernous segments of both internal carotid arteries and mild irregularities of posterior circulation vessels without evidence of large vessel occlusion or aneurysm. Radiation-induced vasculopathy is a recognized delayed complication of cranial irradiation, often presenting 5–25 years after treatment. Pathophysiological mechanisms include endothelial injury, accelerated atherosclerosis, and progressive arterial stenosis. In rare cases, cranial irradiation may also lead to secondary Moyamoya syndrome, characterized by progressive stenosis of the intracranial internal carotid arteries with development of collateral vessels. Although this patient’s vascular imaging did not demonstrate the characteristic collateral network seen in Moyamoya syndrome, it remains an important differential diagnosis in young patients presenting with recurrent stroke after cranial irradiation. In this patient, young age, prior cranial irradiation, multifocal infarcts, and coexisting radiation-induced cavernomas strongly suggest radiationrelated cerebrovascular disease as a major contributor to recurrent stroke. Conclusion Long-term survivors of intracranial germinoma treated with cranial radiotherapy remain at risk of delayed cerebrovascular complications. Early recognition and aggressive secondary stroke prevention, along with continued neurological surveillance, are essential to reduce morbidity in this population.
Ischemic Stroke ; Germinoma

Introduction: Graves’ disease may lead to thyrotoxic cardiomyopathy, a potentially reversible condition following restoration of euthyroidism. Radioiodine (RAI) therapy is commonly used as definitive treatment for patients with long-standing Graves’ disease or poor compliance with antithyroid medications. However, individuals with severe underlying cardiomyopathy may remain vulnerable to cardiovascular instability during the peri-treatment period. Case: We report a 39-year-old male with a 10-year history of Graves’ disease who had previously defaulted on follow-up and was admitted with thyroid storm. Echocardiography during that admission demonstrated severe dilated cardiomyopathy with global hypokinesia and an ejection fraction (EF) of 26%. Following treatment with carbimazole and propranolol, he achieved biochemical euthyroidism and remained clinically stable (NYHA class I). In view of his long-standing disease and prior thyroid storm, he underwent RAI therapy as definitive therapy as per the guidelines. One week following RAI, he developed a persistent cough and progressive dyspnea. Six weeks later, he presented to the emergency department with hypotension (BP 60/31 mmHg) and new-onset atrial fibrillation (heart rate 100 bpm), requiring intubation and inotropic support for cardiogenic shock. Laboratory evaluation showed low free T4 (5.31 pmol/L) with normal thyroid-stimulating hormone (2.1 mIU/L). Repeat echocardiography demonstrated persistent severe left ventricular dysfunction (EF ~25%) without new structural abnormalities. The patient improved rapidly with supportive management and was successfully extubated after stabilization. Although RAI is considered a safe and effective definitive therapy, transient thyroid hormone fluctuations and inflammatory thyroid destruction may occur following treatment. In patients with severe pre-existing cardiomyopathy, these physiological changes may precipitate arrhythmias or acute cardiac decompensation. In this case, new-onset atrial fibrillation in the setting of markedly reduced myocardial reserve likely triggered cardiogenic shock despite biochemical euthyroidism. Conclusion This case highlights that patients with advanced Graves’ cardiomyopathy may remain at risk of acute cardiovascular deterioration following RAI therapy. Careful cardiovascular risk assessment, optimization of heart failure therapy, and close monitoring after definitive treatment should be considered in this high-risk population.

[Objective] To investigate the implementation of emergency transfusion strategy of uncrossmatched type O suspended RBCs based on the single-center clinical practice, which is "emergency transfusion is initiated by the authorized doctor of the emergency department, and no more than 4 U of type O uncrossmatched suspended RBCs are issued within 15 minutes in the transfusion department"(referred as the Practice), so as to provide reference for blood management. [Methods] A retrospective analysis of the information of patients who received uncrossmatched type O suspended RBCs in West China Hospital of Sichuan University from August 2019 to April 2024 was conducted. The analysis included reasons for emergency blood transfusion, time of receiving transfusion application and blood distribution, total bilirubin, indirect bilirubin, lactate dehydrogenase before and after transfusion, blood group of patients, and disease outcome. [Results] From August 2019 to April 2024, 39 cases applied for emergency transfusion of type O suspended RBCs, and a total of 90 U uncrossmatched suspended RBCs were transfused. All patients were Rh(D) positive, including 14 cases of blood group A, 6 cases of blood group B, 16 cases of blood group O, 2 cases of blood group AB, one case of undetermined blood group, and 2 cases with positive antibody screening. The main cause of emergency transfusion of type O suspended RBCs was traffic accident, accounting for 46% (18/39), with a mortality rate at 51.28% (20/39). The cause of death was primary injury, and no adverse reactions were reported. There was no significant difference in total bilirubin (TBIL), indirect bilirubin (IBIL) and lactate dehydrogenase (LDH) before and after blood transfusion (P>0.05). The median duration from admission to receiving transfusion application was 30.20 minutes, and 5.30 minutes from receipt of the application to blood distribution. [Conclusion] The single-center based Practice is safe, but there is room for optimization before the link of blood transfusion application sent to the transfusion department when applying for emergency transfusion of type O suspended RBCs.

Objective To explore the impact factors of misjudge of pneumoconiosis stage based on GBZ70-2015 criteria.Methods Sixty-five case of pneumoconiosis were retrospectively enrolled.Chest high-resolution CT were independently analyzed by one associate chief physician,one attending physician and one resident physician,respectively.The stage of pneumoconiosis was judged,and the inter-observer consistency was observed.Taken the results of 5 experts using Delphi method as gold standard,the impact factors of misjudge of pneumoconiosis stage were analyzed.Results Among 65 cases,there were 42 cases of stage 1,16 cases of stage 2 and 7 cases of stage 3 pneumoconiosis.The inter-observer consistency of pneumoconiosis stage was relatively high(Kappa=0.653),of stage 3 pneumoconiosis was the best(Kappa=0.803),followed by stage 1(Kappa=0.661),while of stage 2 was the lowest(Kappa=0.518).Radiologist lack experience(OR=4.872),the lesions mainly located in the posterior upper area of lungs(OR=2.317),the present of r-type small shadows(OR=3.105)and high CT pulmonary emphysema index(OR=1.214)were all independent impact factors of misjudge of pneumoconiosis stage(all P＜0.05).Conclusion Both the experience of radiologist and lesions'heterogeneity were main impact factors of misjudge of pneumoconiosis stage based on GBZ70-2015 criteria.

Objective:To evaluate the clinical efficacy of inferior gluteus maximus muscle-pedicled myocutaneous flap for reconstruction of stage Ⅳ ischial pressure sores.Methods:Clinical data of patients with stage Ⅳ ischial pressure sores treated between April 2020 and September 2023 at the First People’s Hospital of Yulin were retrospectively analyzed. Underlying comorbidities were treated preoperatively to assure surgical safety. Stage Ⅰ management involved radical debridement of infected tissue followed by vacuum sealing drainage (VSD). Stage Ⅱ reconstruction was performed after inflammation control. An inferior gluteus maximus-pedicled myocutaneous flap was designed laterally to the defect. The muscle component width exceeded the skin paddle width, with the distal muscle extending about 3 cm beyond the skin island. The flap was advanced medially in a V-Y fashion to cover the defect. The donor site was sutured in layers. Postoperative flap viability, wound healing, aesthetic outcomes, and pressure sores recurrence were assessed.Results:A total of 20 patients were included in this study. Among them, 14 were males and 6 were females. The age ranged from 27 to 72 years, with a mean age of 52.3 years. The body mass index (BMI) ranged from 17.8 to 31.3 kg/m 2, with a mean BMI of 21.0 kg/m 2. All had paraplegia secondary to spinal cord injury. Comorbidities included type 2 diabetes and (or) hypertension (10 cases) and ischial osteomyelitis (3 cases). Pressure sores duration ranged from 1 month to 3 years. Defect sizes were 3 cm×4 cm to 5 cm×10 cm (depth: 3-6 cm). Flap sizes matched defects (3 cm×4 cm to 5 cm×10 cm), with muscle dimensions of 2 cm×5 cm×9 cm to 3 cm×8 cm×15 cm. Postoperatively, all 20 flaps showed good blood supply without flap necrosis. The wound healing time ranged from 12 to 22 days (mean: 15 days). Seventeen cases achieved primary wound healing. The remaining three cases developed fat liquefaction at the donor sites, but their wounds eventually healed after dressing changes on postoperative days 18, 20, and 22, respectively. During follow-up (mean: 13 months, range: 6-34 months), the flaps maintained good texture with no recurrence. Conclusion:The inferior gluteus maximus muscle-pedicled myocutaneous flap provides sufficient bulk, simple design, and reliable transposition for dead-space obliteration and surface coverage in stage Ⅳ ischial pressure sores. This technique yields favorable aesthetics and low recurrence rates.

Objective To map the super-enhancers remodeling of intestinal gastric cancer and reveal the tumor biological functions of the super-enhancers and the downstream target genes that may be activated.Methods A total of 31 normal gastric mucosal tissues,23 intestinal gastric cancer tissues and 9 intestinal gastric cancer organoids were collected from the Department of Gastroenterology of Army Medical Center of PLA from January to December 2022.Chromatin targeting histone H3K27ac modified chromatin targeting cleavage under targets and tagmentation(CUT&Tag)sequencing was conducted on above tissues.The remodeling profiles of super-enhancers in intestinal gastric cancer were analyzed and the key target genes were identified based on bioinformation tools.CRISPRi technology was used to intervene with the super-enhancers,the expression of target genes was detected with Western blotting,and the proliferation,migration and invasion abilities were detected by CCK-8 assay and Transwell chambers in the control group and the intervention group.Results There was a significant difference in the signal of super-enhancers between intestinal gastric cancer tissues and normal gastric mucosal tissues(P<0.05),and the active super-enhancers in cancer tissues may be involved in biological processes such as negative regulation of the immune system and cell adhesion.The expression of up-regulated cell migration-inducing protein(CEMIP)in tumor cells was regulated by the super-enhancers,and intervening the super-enhancers down-regulated the expression of CEMIP(P<0.05),and inhibited the cell proliferation,invasion and migration abilities of tumor cells(P<0.05).Conclusion Super-enhancer remodeling is observed in intestinal gastric cancer,and they can up-regulate the expression of CEMIP gene and promote the growth,migration and invasion of cancer cells.