1.Engineered Bacteriophages for The Treatment of Multidrug-resistant Bacterial Infections
Yu-Ying CHEN ; Chun-Mei HUANG ; Jin-Zhi PAN ; De-Liang LIU ; Yang ZHOU ; Gui-Qin DAI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2026;53(6):1581-1596
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.
2.Off-the-shelf human umbilical cord mesenchymal stromal cell product in acute-on-chronic liver failure: A multicenter phase I/II clinical trial.
Lina CUI ; Huaibin ZOU ; Shaoli YOU ; Changcun GUO ; Jundong GU ; Yulong SHANG ; Gui JIA ; Linhua ZHENG ; Juan DENG ; Xiufang WANG ; Ruiqing SUN ; Dawei DING ; Weijie WANG ; Xia ZHOU ; Guanya GUO ; Yansheng LIU ; Zhongchao HAN ; Zhibo HAN ; Yu CHEN ; Ying HAN
Chinese Medical Journal 2025;138(18):2347-2349
3.Comparison of bacterial clearance protocols in mouse nasal cavities
Yimin REN ; Chengshuo WANG ; Xiangyi LIU ; Ying LI ; Shuang LIANG ; Gui ZHANG ; Bing YAN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(8):502-506
OBJECTIVE To investigate the effectiveness of different bacterial cleaning methods and their effects on the general condition,nasal mucosal and systemic inflammation of mice.METHODS A total of 44 mice were randomly divided into six groups:4-antibiotic per os group(4ABX po)with 7 mice,5-antibiotic oral gavage group(5ABX og)with 8 mice,5-antibiotic intranasal group(5ABX in)with 8 mice,and each of their control groups with 7 mice.Body weight,water intake,and peripheral blood routine test of mice were measured.Bacterial culture of nasal lavage fluid(NLF)was performed;mRNA level of inflammatory mediators and histopathological analysis were conducted with mouse nasal mucosa.RESULTS Bacteria were cultured from all control groups,while Bacteria were cultured from all control groups,while one mouse in the 4ABX po group,three mice in the 5ABX og group,and two mice in the 5ABX in group showed no bacterial growth.The number of goblet cells in the nasal mucosa significantly increased in the 5ABX og group compared with its control group(P<0.05).The 5ABX in group exhibited significantly higher counts of peripheral blood lymphocytes and hemoglobin levels,as well as greater nasal mucosal thickness compared with its control group,with a notable decrease in goblet cells(P<0.05).No statistical differences were observed in body weight or the mRNA expression of nasal mucosal inflammatory mediators.CONCLUSION Different combinations of antibiotics and administration routes have varying effects on nasal bacteria,systemic and nasal mucosal inflammation in mice.Therefore,choosing appropriate protocols is crucial for the progression of subsequent research.
4.Textual Research and Identification Analysis of Realgar
Shiyi XU ; Tianxu ZHANG ; Hao FENG ; Li WANG ; Ying LIU ; Juan XI ; Guohua ZHENG ; Xiuqiao ZHANG ; Chun GUI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(11):3240-3254
This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.
5.Application effects of learning pyramid theory combined with constructivism in the standardized training of gastroenterology nurses
Miao CHEN ; Qin MENG ; Xiuping LIU ; Ying WANG ; Xiaoyu CHEN ; Gui JIA
Chinese Journal of Medical Education Research 2025;24(5):686-690
Objective:To investigate the application effects of learning pyramid theory combined with constructivism in the standardized training of nurses in the department of gastroenterology.Methods:We randomly divided 104 gastroenterology nurses who received standardized training from October 2021 to October 2023 into observation group and control group, with 52 nurses in each group. The control group received conventional teaching, while the observation group received a combination of learning pyramid theory and constructivist teaching. The two groups were compared in terms of theoretical and practical scores, core competencies, self-learning abilities, and professional values scores before and after training. SPSS 23.0 was used to perform the t-test. Results:After training, the two groups showed improvements in all the tests; and the scores were all significantly higher in the observation group than in the control group: theoretical knowledge [(88.61±15.62) vs. (81.76±14.27)], skill practice [(82.91±15.17) vs. (76.40±13.82)], Competency Inventory for Registered Nurses scale score [(157.83±21.73) vs. (125.40±15.77)], self-learning ability score [(123.38±21.62) vs. (97.43±15.23)], and Nurse Professional Values scale score [(89.15±14.63) vs. (78.52±12.84)].Conclusions:The teaching model of learning pyramid theory and constructivism theory can enhance standardized training effectiveness for gastroenterology nurses.
6.Evaluation of information quality in autoimmune liver disease-related videos on TikTok
Yanqiu FANG ; Gui JIA ; Yansheng LIU ; Lina CUI ; Yulong SHANG ; Ying HAN
Chinese Journal of Internal Medicine 2025;64(8):759-765
Objective:To evaluate the quality of information on autoimmune liver disease in videos on the TikTok short video platform.Methods:The keyword "autoimmune liver disease" was used to search the top 200 videos on TikTok in the default sorting order. Using the DISCERN video quality assessment tool and the structured content integrity evaluation tool, we assessed the quality of the information in each video in relation to the pertinent disease guidelines. Furthermore, we investigated any relationships between the quality of the videos and their characteristics (likes, comments, retweets, days and duration of uploading).Results:A total of 140 videos were included, 96.4% of which were provided by medical professionals. The content completeness scores for each dimension were as follows: definition, 1.0 (0.0, 1.0); symptoms, 0.0 (0.0, 1.0); risk factors, 0.0 (0.0, 0.5); assessment, 0.5 (0.0, 1.5); management, 0.5 (0.0, 1.0); and outcome, 0.0 (0.0, 1.0). Furthermore, 91.4% of videos with DISCERN scores of ≤50 were of "fair" quality or below. Additionally, the difference in DISCERN scores between videos from different publishers was not statistically significant ( P>0.05). The number of likes, comments, favorites, retweets, and video duration had a strong positive correlation with the overall DISCERN score ( r=0.17, 0.18, 0.25, 0.26, 0.44, all P<0.05). Conclusions:The overall quality of videos related to autoimmune liver disease on the TikTok video platform is low. Therefore, publishers should focus on the comprehensiveness and accuracy of the information. Additionally, the TikTok platform should optimize its video review mechanism to provide the public with more accurate and reliable health information.
7.Prenatal ultrasound diagnosis of fetal hypoplastic left heart syndrome with left ventricular enlargement:a case report
Chen ZHU ; Fan-gui ZHAO ; Ying-liu YAN ; Cai-xia LEI ; Ting YU ; Chen-yan ZHAO ; Ru LIN ; Yun-yun REN
Fudan University Journal of Medical Sciences 2025;52(1):143-146
The pregnant woman was 30 years old,G2P0.This singleton pregnancy at 22 weeks of gestation was screened for second-trimester ultrasound malformations,suggesting fetal aortic valve atresia,aortic stenosis with reverse blood flow,mitral valve atresia,and markedly enlarged left ventricle,which was considered for the diagnosis of hypoplastic left heart syndrome(HLHS).The pregnancy was terminated at our hospital and subsequently underwent genetic testing with results of heterozygous variants in the NOTCH1 gene,which can cause aortic valve disease type 1.The findings of the fetal autopsy were aortic valve atresia,mitral valve widening and thickening,and left ventricular enlargement with myocardial infarction.This report focuses on the ultrasound characteristics of HLHS with left ventricular enlargement and its hemodynamic changes in order to improve clinicians'understanding of the progressive changes in the disease phenotype of HLHS.
8.Cross-sectional survey of healthcare-associated infection in 5 736 medical institutions across China in 2024
Cui ZENG ; Wuqiang GAO ; Fu QIAO ; Hui ZHAO ; Xu FANG ; Linping LI ; Xiuwen CHEN ; Jiansen CHEN ; Dan LI ; Yuan ZHOU ; Lingli YU ; Qinglan MENG ; Xia MOU ; Lijuan XIONG ; Weiguang LI ; Ding LIU ; Jiaqing XIAO ; Limei OU ; Baozhen LI ; Jun YIN ; Haojun ZHANG ; Qiang FU ; Qun LU ; Biao WU ; Ya-wei XING ; Shumei SUN ; Shuncai WANG ; Longmin DU ; Jingping ZHANG ; Wen-ying HE ; Gui CHENG ; Nan REN ; Xun HUANG ; Anhua WU
Chinese Journal of Infection Control 2025;24(11):1572-1583
Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27%.The number of HAI episodes was 38 032,and case prevalence rate was 1.38%.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66%to 2.35%.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65%.The most common infection site was the lower respiratory tract(44.66%),followed by the urinary tract(12.94%),surgical site(9.32%),upper respiratory tract(7.02%),and bloodstream infection(5.78%).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02%),department of neurosurgery(5.51%),and department(group)of hematology(5.34%).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10%)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76%),Pseudomonas aeruginosa(13.33%),Escherichia coli(12.79%),Acinetobacter baumannii(9.23%),and Staphylococcus aureus(7.88%).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71%.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18%.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46%.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.
9.Application effects of learning pyramid theory combined with constructivism in the standardized training of gastroenterology nurses
Miao CHEN ; Qin MENG ; Xiuping LIU ; Ying WANG ; Xiaoyu CHEN ; Gui JIA
Chinese Journal of Medical Education Research 2025;24(5):686-690
Objective:To investigate the application effects of learning pyramid theory combined with constructivism in the standardized training of nurses in the department of gastroenterology.Methods:We randomly divided 104 gastroenterology nurses who received standardized training from October 2021 to October 2023 into observation group and control group, with 52 nurses in each group. The control group received conventional teaching, while the observation group received a combination of learning pyramid theory and constructivist teaching. The two groups were compared in terms of theoretical and practical scores, core competencies, self-learning abilities, and professional values scores before and after training. SPSS 23.0 was used to perform the t-test. Results:After training, the two groups showed improvements in all the tests; and the scores were all significantly higher in the observation group than in the control group: theoretical knowledge [(88.61±15.62) vs. (81.76±14.27)], skill practice [(82.91±15.17) vs. (76.40±13.82)], Competency Inventory for Registered Nurses scale score [(157.83±21.73) vs. (125.40±15.77)], self-learning ability score [(123.38±21.62) vs. (97.43±15.23)], and Nurse Professional Values scale score [(89.15±14.63) vs. (78.52±12.84)].Conclusions:The teaching model of learning pyramid theory and constructivism theory can enhance standardized training effectiveness for gastroenterology nurses.
10.Study on the efficacy of automatic-controlled pressure cupping for lumbar disc herniation.
Bo-Chen PENG ; Min-Shan FENG ; Li LI ; Gui-Ju REN ; Yi-Zhen YUAN ; Li-Jie CHANG ; Shu-Ying REN ; Liu ZENG ; Guang-Wei LIU ; Li-Guo ZHU ; Na YUAN
China Journal of Orthopaedics and Traumatology 2025;38(11):1133-1138
OBJECTIVE:
To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping.
METHODS:
A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety.
RESULTS:
All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001).
CONCLUSION
Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans
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Female
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Male
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Intervertebral Disc Displacement/physiopathology*
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Middle Aged
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Adult
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Lumbar Vertebrae/physiopathology*
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Cupping Therapy/methods*
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Pressure
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Aged
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Treatment Outcome

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