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.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To investigate the mammographic imaging features of breast cancer and its correlation with microvascular density(MVD).Methods A total of 86 patients with breast cancer confirmed by surgical pathology in Xinjiang Production and Construction Corps 7th Division Hospital from January 2019 to December 2022 were selected as the research objects.According to the modified Bloom Richard-son scoring system,the breast cancer patients were classified into histological grade Ⅰ(n=22),grade Ⅱ(n=25)and grade Ⅲ(n=39).All patients underwent preoperative mammographic imaging examination.Immunohistochemistry staining was performed and MVD count was conducted after operation.Spearman rank correlation was used to analyze the correlation between MVD of breast cancer with different histo-logical grades and mammographic imaging features.Results The microvascular positive expression rate of breast cancer lesions was 100%,the MVD counts per visual field were 14～276 vessels,with an average of(72.58±16.37)vessels,of which the MVD counts of patients with histological grade Ⅰ to Ⅱ were 14 to 175 vessels,with an average of(42.10±13.51)vessels;the MVD counts of patients with histological grade Ⅲ was 22～276 vessels,with an average of(93.82±22.17)vessels.The MVD counts of patients with histological grade Ⅲ was signifi-cantly higher than that of patients with histological grade Ⅰ to Ⅱ,with statistically significant difference(t=19.627,P<0.001).The incidences of irregular margin,spicular sign,axillary lymph node metastasis and fine particle calcification in patients with histological gradeⅢ were higher than those in patients with histological grade Ⅰ to Ⅱ,with statistically significant difference(P<0.05).The MVD counts of breast cancer patients with irregular margin,spicular sign,axillary lymph node metastasis and fine particle calcification were higher than those of patients with smooth margin and without spicular sign,axillary lymph node metastasis or fine particle calcification,which was positively correlated with histological grades(P<0.05).Conclusion Some mammographic imaging features of breast cancer can reflect tumor angiogenesis to a certain extent,which can provide important reference for the treatment and prognosis of the disease,with certain clinical value.

This study analyzed the demographic characteristics and clinically significant inflammatory index changes in listeriosis cases in China from 2010 to 2023.The aim was to understand Listeria monocytogenes susceptibility,to provide a reference for listeriosis prevention and control.Records in three Chinese databases—the China Knowledge Network,Wanfang Database,and VIP Database—from January 1,2010,to December 31,2023,were searched.Statistical analysis was conducted on the clinical features and epidemiological information for all identified cases.A total of 693 cases of listeriosis were included:482 occurring during the perinatal period and 211 occurring outside the perinatal period.The average mortality rate was 17.2%(119/693).The predominant clinical manifestations of listeriosis in neonatal patients during the perinatal period were sepsis(75.5%,241/319)and meningitis(41.1%,131/319).The mortality rate among neonatal patients was 27.1%(76/280).In patients in the non-perinatal period,meningitis(70.1%,148/211)and sepsis(43.6%,92/211)were the main clinical manifestations,and the average patient age was 47.2 years.Among patients of known age,the highest prevalence was observed in the 40-64 year age group,which accounted for 44.9%(44/98).Sixty-one cases had no other underlying diseases before infection.Reported cases of listeriosis occurred in 27 provinces(municipalities,and autonomous region)in China,and Beijing reported the most cases,accounting for 23.7%(164/693).L.monocytogenes was sensitive to β-lactam drug treatment but showed differing degrees of drug resistance.Among 145 cases,12 were resistant to penicillin,and 16 were resistant to oxacillin.Listeriosis is a foodborne disease with a high mortality rate,particularly among neonates.With the continuing emergence of drug-resistant strains,standardizing and strengthening prevention and treatment measures for this disease as early as possible are essential.

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

OBJECTIVE: The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms. METHODS: Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA). RESULTS: Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation. CONCLUSION Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; 23(4): 398-414.
Animals ; Male ; Rats, Sprague-Dawley ; STAT3 Transcription Factor/metabolism* ; alpha7 Nicotinic Acetylcholine Receptor/metabolism* ; Janus Kinase 2/metabolism* ; Atrial Fibrillation/metabolism* ; Vagus Nerve/physiopathology* ; Rats ; Acupuncture Therapy ; Signal Transduction ; Macrophages/metabolism* ; Inflammation/therapy*