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.Traditional Chinese Medicine Intervenes in Endoplasmic Reticulum Stress to Treat Diabetic Microvascular Complications:A Review
Zhenlong ZHOU ; Yu DUAN ; Yutian PANG ; Ying JIA ; Mingwei LI ; Hongyu SHA ; Haichun ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):293-305
Diabetic microvascular complications (DMC) are major chronic complications of diabetes,primarily including diabetic kidney disease (DKD),diabetic retinopathy (DR),diabetic cardiomyopathy (DCM),and diabetic peripheral neuropathy (DPN). These complications significantly impact patients' quality of life and prognosis. Modern medicine primarily focuses on symptomatic control in the treatment of DMC,with limited ability to reverse the disease progression. Endoplasmic reticulum stress (ERS),as a central event under hyperglycemic toxicity,is not only a key cause of pancreatic β-cell dysfunction (reduced insulin synthesis and secretion) but also a core driver of damage in various target organs of DMC. It activates three signaling pathways of the unfolded protein response (UPR)-inositol-requiring enzyme 1 (IRE1),activating transcription factor 6 (ATF6),and protein kinase R-like endoplasmic reticulum kinase (PERK),intertwining processes such as autophagy,apoptosis,oxidative stress,and calcium homeostasis imbalance. Traditional Chinese medicine (TCM) offers multi-target and multi-pathway therapeutic advantages and can curb the pathological progression of DMC by regulating ERS. This article systematically reviews the relationships of ERS with pancreatic β-cell function,insulin synthesis,and insulin secretion,and elucidates the core signaling pathways through which ERS mediates DMC. Furthermore,it categorizes and summarizes experimental evidence and mechanisms of single medicinal herbs and their extracts,TCM compound formulas,and modern TCM preparations in regulating ERS for the treatment of various DMC subtypes. Finally,this article proposes ERS as a molecular bridge for integrating traditional Chinese and Western medicine in DMC treatment. Future research should leverage emerging technologies such as network pharmacology,multi-omics analysis,and nano-formulations to establish a synergistic network combining modern hypoglycemic drugs and TCM regulation of ERS. This approach is expected to achieve dual efficacy,enhance drug targeting and bioavailability,deepen the understanding of scientific connotation of TCM,and pave new avenues for the prevention and treatment of DMC.
3.Traditional Chinese Medicine Intervenes in Endoplasmic Reticulum Stress to Treat Diabetic Microvascular Complications:A Review
Zhenlong ZHOU ; Yu DUAN ; Yutian PANG ; Ying JIA ; Mingwei LI ; Hongyu SHA ; Haichun ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):293-305
Diabetic microvascular complications (DMC) are major chronic complications of diabetes,primarily including diabetic kidney disease (DKD),diabetic retinopathy (DR),diabetic cardiomyopathy (DCM),and diabetic peripheral neuropathy (DPN). These complications significantly impact patients' quality of life and prognosis. Modern medicine primarily focuses on symptomatic control in the treatment of DMC,with limited ability to reverse the disease progression. Endoplasmic reticulum stress (ERS),as a central event under hyperglycemic toxicity,is not only a key cause of pancreatic β-cell dysfunction (reduced insulin synthesis and secretion) but also a core driver of damage in various target organs of DMC. It activates three signaling pathways of the unfolded protein response (UPR)-inositol-requiring enzyme 1 (IRE1),activating transcription factor 6 (ATF6),and protein kinase R-like endoplasmic reticulum kinase (PERK),intertwining processes such as autophagy,apoptosis,oxidative stress,and calcium homeostasis imbalance. Traditional Chinese medicine (TCM) offers multi-target and multi-pathway therapeutic advantages and can curb the pathological progression of DMC by regulating ERS. This article systematically reviews the relationships of ERS with pancreatic β-cell function,insulin synthesis,and insulin secretion,and elucidates the core signaling pathways through which ERS mediates DMC. Furthermore,it categorizes and summarizes experimental evidence and mechanisms of single medicinal herbs and their extracts,TCM compound formulas,and modern TCM preparations in regulating ERS for the treatment of various DMC subtypes. Finally,this article proposes ERS as a molecular bridge for integrating traditional Chinese and Western medicine in DMC treatment. Future research should leverage emerging technologies such as network pharmacology,multi-omics analysis,and nano-formulations to establish a synergistic network combining modern hypoglycemic drugs and TCM regulation of ERS. This approach is expected to achieve dual efficacy,enhance drug targeting and bioavailability,deepen the understanding of scientific connotation of TCM,and pave new avenues for the prevention and treatment of DMC.
4.Clinical Efficacy of Modified Yuejuwan in Treatment of Thyroid Cysts After Microwave Ablation
Xiaojing YU ; Ying ZHOU ; Wei XING ; Guolei LI ; Yingying LOU ; Yashi WANG ; Wenmin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):11-18
ObjectiveTo observe the clinical efficacy of modified Yuejuwan in the treatment of thyroid cysts after microwave ablation. MethodsA total of 90 patients with thyroid cysts who met the inclusion criteria and treated in the First Affiliated Hospital of Hebei University of Chinese Medicine from September 2022 to December 2023 were randomly assigned to either the control group or the observation group, with 45 patients in each group. The control group received conventional postoperative drug treatment and was followed up regularly. The observation group was additionally administrated with modified Yuejuwan for one month and followed up regularly. The alterations in volume, thyroid function parameters [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)], quality of life scores, and clinical efficacy were monitored and compared between the two groups. Additionally, the safety profile was appraised. ResultsAfter treatment, both the observation group and the control group showed a reduction in cyst volume (P<0.05), and the observation group exhibited a more significant reduction in cyst volume than the control group (P<0.05). After treatment, both the observation group and the control group showed a decrease in TSH level and increases in FT3 and FT4 levels (P<0.05), and the changes were more significant in the observation group (P<0.05). In addition, both groups exhibited elevations in the quality of life scores (P<0.05). Moreover, the observation group showed more increments in physiological, psychological, and social scores than the control group (P<0.05). The total response rate of the observation group was higher than that of the control group (Z=-2.516, P<0.05). The incidence of adverse reactions was similar between the two groups, with no statistically significant difference. ConclusionModified Yuejuwan is effective in the treatment of thyroid cysts after microwave ablation. It can promote the absorption of cysts, improve the thyroid function and quality of life, and has high safety.
5.Clinical Efficacy of Modified Yuejuwan in Treatment of Thyroid Cysts After Microwave Ablation
Xiaojing YU ; Ying ZHOU ; Wei XING ; Guolei LI ; Yingying LOU ; Yashi WANG ; Wenmin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):11-18
ObjectiveTo observe the clinical efficacy of modified Yuejuwan in the treatment of thyroid cysts after microwave ablation. MethodsA total of 90 patients with thyroid cysts who met the inclusion criteria and treated in the First Affiliated Hospital of Hebei University of Chinese Medicine from September 2022 to December 2023 were randomly assigned to either the control group or the observation group, with 45 patients in each group. The control group received conventional postoperative drug treatment and was followed up regularly. The observation group was additionally administrated with modified Yuejuwan for one month and followed up regularly. The alterations in volume, thyroid function parameters [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)], quality of life scores, and clinical efficacy were monitored and compared between the two groups. Additionally, the safety profile was appraised. ResultsAfter treatment, both the observation group and the control group showed a reduction in cyst volume (P<0.05), and the observation group exhibited a more significant reduction in cyst volume than the control group (P<0.05). After treatment, both the observation group and the control group showed a decrease in TSH level and increases in FT3 and FT4 levels (P<0.05), and the changes were more significant in the observation group (P<0.05). In addition, both groups exhibited elevations in the quality of life scores (P<0.05). Moreover, the observation group showed more increments in physiological, psychological, and social scores than the control group (P<0.05). The total response rate of the observation group was higher than that of the control group (Z=-2.516, P<0.05). The incidence of adverse reactions was similar between the two groups, with no statistically significant difference. ConclusionModified Yuejuwan is effective in the treatment of thyroid cysts after microwave ablation. It can promote the absorption of cysts, improve the thyroid function and quality of life, and has high safety.
6.In vivo production of anti-CD19 CAR-T cells with T cell-targeted engineered exosomes to evaluate cytotoxicity against lymphoma cells
Dong TING ; Zhou YING ; Yu BOYU ; Xia XUEJIAO ; Ma YIGE ; Ma YAN ; Gao YANG ; Zhou MENGYING ; Wang CHANGJUN ; Li QIUYI ; Gu CHAOJIANG
Chinese Journal of Clinical Oncology 2025;52(6):279-286
Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.
7.Differences in mercury dissolution from HgS-containing traditional medicines under simulated gastrointestinal conditions
Ming ZHANG ; Yuan-can XIAO ; Jing ZHAO ; Hai-ying TONG ; Xiao-yu WANG ; Wen-bin ZHOU ; Hong-tao BI ; Li-xin WEI
Chinese Traditional Patent Medicine 2025;47(8):2607-2611
AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.
8.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
9.Expert consensus on intraoperative repositioning for patients with spine fracture and dislocation (version 2025)
Dongmei BIAN ; Ke SUN ; Ningbo CHEN ; Caixia BAI ; Miao WANG ; Yafeng QIAO ; Fei WANG ; Hong WANG ; Feng TIAN ; Mei YAN ; Meng BAI ; Linjuan ZHANG ; Liyan ZHAO ; Yaqing CUI ; Xue JIANG ; Leling FENG ; Ning NING ; Junqin DING ; Lan WEI ; Yonghua ZHAI ; Yu ZENG ; Zengmei ZHANG ; Jiqun HE ; Fenggui BIE ; Hong CHEN ; Zengyan WANG ; Li LI ; Li ZHANG ; Yaying ZHOU ; Bing SHAO ; Ying WANG ; Caixia XIE ; Yanfeng YAO ; Jingjing AN ; Wen SHI ; Xiongtao LIU ; Xiaoyan AN ; Ning NAN ; Lan LI ; Xiaohui GOU ; Qiaomei LI ; Xiuting WU ; Yuqin ZHANG ; Jing LIU ; Fusen XIANG ; Xu XU ; Na MEI ; Jiao ZHOU ; Shan FAN ; Qian WANG ; Shuixia LI
Chinese Journal of Trauma 2025;41(2):138-147
Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.
10.Chinese expert consensus on community-based three-level comprehensive prevention and treatment of Alzheimer's disease(2025 edition)
Ying WANG ; Liang SUN ; Gang WANG ; Chunbo LI ; Houguang ZHOU ; Yifeng DU ; Yunpeng CAO ; Kai WANG ; Jiewen ZHANG ; Yao YAO ; Shangfeng TANG ; Yurong JING ; Qihua XU ; Xizhe PENG ; Yu HU ; Haimei QI
Chinese Journal of Geriatrics 2025;44(3):227-237
Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

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