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

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

OBJECTIVE: To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome. METHODS: From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded. RESULTS: Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment. CONCLUSIONS The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Rhinitis, Allergic/drug therapy* ; Female ; Adult ; Double-Blind Method ; Quality of Life ; Qi ; Middle Aged ; Loratadine/therapeutic use* ; Medicine, Chinese Traditional ; Syndrome ; Lung/drug effects* ; Young Adult ; Treatment Outcome

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Objective:To explore the incidence characteristics and correlation analysis of Western dryness syndrome in pulmonary tuberculosis patients in Moyu County,Hetian Prefecture,Xinjiang,and to provide a basis for the prevention and treatment strategies and effectiveness evaluation of pulmonary tuberculosis in Xinjiang.Methods:89 confirmed cases of pulmonary tuberculosis in Moyu County,Hotian Prefecture,Xinjiang from October 2023 to October 2024 were selected as the case group,and 117 healthy individuals matched with the case group in terms of gender,age,and education level in Moyu County,Hotian Prefecture,Xinjiang during the same period were selected as the control group.The general information and incidence of Northwest dryness syndrome between two groups were compared.The incidence and severity of Northwest dryness syndrome in tuberculosis patients,as well as the main and secondary syndrome scores of Northwest dryness syndrome were analyzed.The influencing factors of pulmonary tuberculosis were analyzed.The scores of the main syndrome of Northwest dryness syndrome(lung wei kong pi dryness syndrome)and the concurrent syndrome of Northwest dryness syndrome(heart kidney yin deficiency syndrome,lung heart spleen wind fire dryness syndrome,liver kidney essence blood deficiency syndrome,spleen stomach dampness syndrome,spleen stomach yin deficiency syndrome)between the control group and the case group were compared.The correlation between pulmonary tuberculosis and the on set of Northwest dryness syndrome were analyzed by Spearman rank sum test.Results:There was no significant difference between the control group and the case group in terms of body mass index(BMI),age,education level,gender,etc.(P＞0.05).The incidence of Northwest dryness syndrome in the case group was significantly higher than that in the control group(P＜0.05).The Northwest Dry Syndrome Scale score in the severe group was higher than that in the mild and moderate groups,and the Northwest Dry Syndrome Scale score in the moderate group was higher than that in the mild group(P＜0.05).Among 89 patients with pulmonary tuberculosis,the main syndrome of lung wei kong pi dryness syndrome had the highest number of cases,totaling 42 cases(47.19％).The highest number of concurrent syndromes were heart kidney yin deficiency syndrome,totaling 36 cases(40.45％),followed by spleen stomach yin deficiency syndrome,totaling 35 cases(39.33％).The results showed that suffering from Northwest dryness syndrome was a risk factor for pulmonary tuberculosis(P＜0.05).There were significant differences in the scores of the main syndrome of Northwest dryness(Lung Wei Kong Pi dryness syndrome),the concurrent syndrome of Northwest dryness(Lung Heart Spleen Wind Fire dryness syndrome),and the concurrent syndrome of Northwest dryness(Spleen Stomach Yin Deficiency syndrome)between the control group and the case group(P＜0.05).There was no significant difference in the scores of Northwest dryness syndrome(liver and kidney essence and blood deficiency syndrome),Northwest dryness syndrome(heart and kidney yin deficiency syndrome),and Northwest dryness syndrome(spleen and stomach dampness syndrome)between the control group and the case group(P＞0.05).The score of pulmonary tuberculosis syndrome was positively correlated with various types of Northwest dryness syndrome(P＜0.05),and there was a significant correlation at the 0.001 level between pulmonary Wei Kong Pi dryness syndrome,pulmonary heart spleen wind fire dryness syndrome,and spleen stomach dampness syndrome(P＜0.05).The correlation between liver and kidney essence and blood deficiency syndrome and spleen and stomach yin deficiency syndrome is significant at the 0.01 level(P＜0.05).The correlation between heart and kidney yin deficiency syndrome is significant at the 0.05 level(P＜0.05).Conclusion:The northwest dryness syndrome is related to the occurrence of pulmonary tuberculosis in Moyu County,Hotan Prefecture,Xinjiang,and is a risk factor for the occurrence of pulmonary tuberculosis.There is a significant positive correlation between the pulmonary tuberculosis syndrome score and various types of northwest dryness syndrome,among which the lung wei kong pi dryness syndrome,lung heart spleen wind fire dryness syndrome,and spleen stomach dampness syndrome have the most significant impact on the pulmonary nucleus syndrome score.

Objective:To explore the incidence characteristics and correlation analysis of Western dryness syndrome in pulmonary tuberculosis patients in Moyu County,Hetian Prefecture,Xinjiang,and to provide a basis for the prevention and treatment strategies and effectiveness evaluation of pulmonary tuberculosis in Xinjiang.Methods:89 confirmed cases of pulmonary tuberculosis in Moyu County,Hotian Prefecture,Xinjiang from October 2023 to October 2024 were selected as the case group,and 117 healthy individuals matched with the case group in terms of gender,age,and education level in Moyu County,Hotian Prefecture,Xinjiang during the same period were selected as the control group.The general information and incidence of Northwest dryness syndrome between two groups were compared.The incidence and severity of Northwest dryness syndrome in tuberculosis patients,as well as the main and secondary syndrome scores of Northwest dryness syndrome were analyzed.The influencing factors of pulmonary tuberculosis were analyzed.The scores of the main syndrome of Northwest dryness syndrome(lung wei kong pi dryness syndrome)and the concurrent syndrome of Northwest dryness syndrome(heart kidney yin deficiency syndrome,lung heart spleen wind fire dryness syndrome,liver kidney essence blood deficiency syndrome,spleen stomach dampness syndrome,spleen stomach yin deficiency syndrome)between the control group and the case group were compared.The correlation between pulmonary tuberculosis and the on set of Northwest dryness syndrome were analyzed by Spearman rank sum test.Results:There was no significant difference between the control group and the case group in terms of body mass index(BMI),age,education level,gender,etc.(P＞0.05).The incidence of Northwest dryness syndrome in the case group was significantly higher than that in the control group(P＜0.05).The Northwest Dry Syndrome Scale score in the severe group was higher than that in the mild and moderate groups,and the Northwest Dry Syndrome Scale score in the moderate group was higher than that in the mild group(P＜0.05).Among 89 patients with pulmonary tuberculosis,the main syndrome of lung wei kong pi dryness syndrome had the highest number of cases,totaling 42 cases(47.19％).The highest number of concurrent syndromes were heart kidney yin deficiency syndrome,totaling 36 cases(40.45％),followed by spleen stomach yin deficiency syndrome,totaling 35 cases(39.33％).The results showed that suffering from Northwest dryness syndrome was a risk factor for pulmonary tuberculosis(P＜0.05).There were significant differences in the scores of the main syndrome of Northwest dryness(Lung Wei Kong Pi dryness syndrome),the concurrent syndrome of Northwest dryness(Lung Heart Spleen Wind Fire dryness syndrome),and the concurrent syndrome of Northwest dryness(Spleen Stomach Yin Deficiency syndrome)between the control group and the case group(P＜0.05).There was no significant difference in the scores of Northwest dryness syndrome(liver and kidney essence and blood deficiency syndrome),Northwest dryness syndrome(heart and kidney yin deficiency syndrome),and Northwest dryness syndrome(spleen and stomach dampness syndrome)between the control group and the case group(P＞0.05).The score of pulmonary tuberculosis syndrome was positively correlated with various types of Northwest dryness syndrome(P＜0.05),and there was a significant correlation at the 0.001 level between pulmonary Wei Kong Pi dryness syndrome,pulmonary heart spleen wind fire dryness syndrome,and spleen stomach dampness syndrome(P＜0.05).The correlation between liver and kidney essence and blood deficiency syndrome and spleen and stomach yin deficiency syndrome is significant at the 0.01 level(P＜0.05).The correlation between heart and kidney yin deficiency syndrome is significant at the 0.05 level(P＜0.05).Conclusion:The northwest dryness syndrome is related to the occurrence of pulmonary tuberculosis in Moyu County,Hotan Prefecture,Xinjiang,and is a risk factor for the occurrence of pulmonary tuberculosis.There is a significant positive correlation between the pulmonary tuberculosis syndrome score and various types of northwest dryness syndrome,among which the lung wei kong pi dryness syndrome,lung heart spleen wind fire dryness syndrome,and spleen stomach dampness syndrome have the most significant impact on the pulmonary nucleus syndrome score.

AIM To investigate the effects of ampelopsin-mediated autophagy and apoptosis of human cervical cancer SiHa cells.METHODS After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group,the 3-MA+ampelopsin group and the Z-VAD-FMK+ampelopsin group,the cells had their cell proliferation inhibition rate detected by MTT method.After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group and the 3-MA+ampelopsin group,the cells had their morphological changes observed under electron microscope and their apoptosis detected by Hoechst33258 and AnnexinV-FITC/PI staining.After 24 h corresponding administration and culture among the control group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group and the Z-VAD-FMK+ampelopsin group,the cells had their autophagy and ultrastructure observed by MDC method and transmission electron microscopy.After 12 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group,the 3-MA+ampelopsin group or control group,the Z-VAD-FMK (50 μmol/L) group,the ampelopsin (80 μmol/L) group,and the Z-VAD-FMK+ampelopsin group,the cells had their protein expressions of cleaved-PARP,cleaved-Caspase3,Bax,Bcl-2,Atg13,Beclin-1,LC3,and P62 detected by Western blot.RESULTS Compared with the control group,the ampelopsin group displayed enhanced proliferation inhibition of SiHa and C-33A cells (P<0.01).Compared with the ampelopsin group,the groups intervened with 3-MA+ampelopsin and Z-VAD-FMK+ampelopsin showed more significantly inhibited proliferation of the two cell lines (P<0.01),and decreased number of living cells.Compared with the ampelopsin group,the 3-MA+ampelopsin group showed increased bright blue fluorescence and apoptosis rate of SiHa cells (P<0.05),increased cleaved PARP,Bax,and P62 protein expressions (P<0.01),and decreased LC3Ⅱ/LC3Ⅰ ratio and Bcl-2 protein expression (P<0.01).Compared with the ampelopsin group,the Z-VAD-FMK+ampelopsin group demonstrated increased green dot fluorescence and number of autophagosomes and autopolysosomes,increased LC3Ⅱ/LC3Ⅰ ratio,Atg13 and Beclin-1 protein expression (P<0.05,P<0.01);and decreased protein expressions of P62,cleaved-PARP,cleaved-Caspase3 (P<0.05,P<0.01).CONCLUSION Being an antagonist of human cervical carcinoma SiHa cells,ampelopsin can induce autophagy and apoptosis of the cells through its key target on Beclin-1/Bcl-2.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.