1.Discovery of a novel polymyxin adjuvant against multidrug-resistant gram-negative bacteria through oxidative stress modulation.
Taotao LU ; Hongguang HAN ; Chaohui WU ; Qian LI ; Hongyan HU ; Wenwen LIU ; Donglei SHI ; Feifei CHEN ; Lefu LAN ; Jian LI ; Shihao SONG ; Baoli LI
Acta Pharmaceutica Sinica B 2025;15(3):1680-1695
Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.
2.Formulation patterns and potential targets of traditional Chinese medicine in the treatment of pneumoconiosis based on network pharmacology
Liting WU ; Yu XU ; Yuanfang CHEN ; Baoli ZHU ; Ming XU ; Lei HAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(9):679-686
Objective:To explore the formulation patterns and potential targets of traditional Chinese medicine (TCM) in the treatment of pneumoconiosis using data mining, network pharmacology, and Mendelian randomization (MR) .Methods:In November 2023, prescription data for TCM compound treatments of pneumoconiosis from the past five years were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases. The formulation patterns of TCM for pneumoconiosis were analyzed based on drug frequency, association rules, and cluster analysis, followed by the identification of core drugs. Network pharmacology and MR analysis were then applied to determine the potential targets for pneumoconiosis treatment.Results:A total of 100 TCM prescriptions were included, involving 182 herbs, with 15 high-frequency herbs. A total of 24 strong association rules were identified, including 16 herbs. Cluster analysis identified three groups of drug combinations. The core drug combination, "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root" was determined, which interacted with 47 common targets associated with pneumoconiosis. Further protein-protein interaction (PPI) analysis identified 18 core targets, and MR analysis confirmed that Caspase-3 (CASP3) and Cathepsin B (CTSB) were risk factors for pneumoconiosis ( OR=1.35, 1.44; P=0.038, 0.038) . Conclusion:The core drug combination for the treatment of pneumoconiosis with TCM is "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root". The medication mainly focuses on tonifying lung qi, moistening dryness and stopping coughing, circulating blood and transforming stasis, which are supplemented with herbs for nourishing yin and moistening dryness, warming yang and dissipating cold. Finally, the key targets for treating pneumoconiosis are screened out, providing an important basis for the development of therapeutic drugs for it.
3.Methodological Problems and Solutions Commonly Encountered in Scientific Reviews of Investor Initiated Trial in the Field of Traditional Chinese Medicine
Fang HAN ; Jia XU ; Baoli LIU ; Qingquan LIU ; Bin LI ; Jing HU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(6):1509-1513
The number of investor initiated trial(IIT)in the field of traditional Chinese medicine(TCM)in China has been increasing year by year,but there are still many problems about their scientific validity.Scientific review is the top priority of IIT management,which is of great significance to improve the quality of IIT.Considering the characteristics of IIT in the field of TCM,randomized controlled trials and discuss common methodological problems in the scientific review process of IIT are focused on,such as non-standard placebo setting,unclear research hypothesis or improper selection of hypothesis test type,inappropriate sample size estimation methods,insufficient characteristics of TCM in outcome measures,unreasonable statistical analysis methods,etc.At the same time,corresponding solutions are proposed to increase the scientific and credibility of IIT,thus improving the research quality of IIT in TCM.
4.The Problems and Solutions in the Design and Record of TCM Clinical Research Case Report Form
Fang HAN ; Kegang CAO ; Ying GAO ; Baoli LIU ; Tiantian ZHOU ; Jing HU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):533-538
Case report form(CRF)is an important tool to obtain clinical research data.Scientifically designed and properly recorded CRF is of great significance to improve the quality of clinical research.The author summarized the common problems existing in the design and recording of CRF in traditional Chinese medicine(TCM)clinical studies,including:①Delayed design time point.②Unstandardized CRF design,recording and modification.③Imperfect records of combined medication/therapy.④Insufficient quantification of syndrome efficacy indicators and objectification of tongue and pulse.⑤ Insufficient protection of subjects' privacy.⑥ Unstandardized records of adverse events.Accordingly,this paper discusses some solutions to provide reference for other TCM researchers,including:①Advance CRF design time.②Standardize CRF design,recording and modification.③Design drug combinations/therapies according to Clinical Data Acquisition Standards Harmonization(CDASH).④Standardization of syndrome and tongue and pulse.⑤Use of subject identification codes to protect privacy.⑥AE records should vary from study to study.
5.Formulation patterns and potential targets of traditional Chinese medicine in the treatment of pneumoconiosis based on network pharmacology
Liting WU ; Yu XU ; Yuanfang CHEN ; Baoli ZHU ; Ming XU ; Lei HAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(9):679-686
Objective:To explore the formulation patterns and potential targets of traditional Chinese medicine (TCM) in the treatment of pneumoconiosis using data mining, network pharmacology, and Mendelian randomization (MR) .Methods:In November 2023, prescription data for TCM compound treatments of pneumoconiosis from the past five years were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases. The formulation patterns of TCM for pneumoconiosis were analyzed based on drug frequency, association rules, and cluster analysis, followed by the identification of core drugs. Network pharmacology and MR analysis were then applied to determine the potential targets for pneumoconiosis treatment.Results:A total of 100 TCM prescriptions were included, involving 182 herbs, with 15 high-frequency herbs. A total of 24 strong association rules were identified, including 16 herbs. Cluster analysis identified three groups of drug combinations. The core drug combination, "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root" was determined, which interacted with 47 common targets associated with pneumoconiosis. Further protein-protein interaction (PPI) analysis identified 18 core targets, and MR analysis confirmed that Caspase-3 (CASP3) and Cathepsin B (CTSB) were risk factors for pneumoconiosis ( OR=1.35, 1.44; P=0.038, 0.038) . Conclusion:The core drug combination for the treatment of pneumoconiosis with TCM is "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root". The medication mainly focuses on tonifying lung qi, moistening dryness and stopping coughing, circulating blood and transforming stasis, which are supplemented with herbs for nourishing yin and moistening dryness, warming yang and dissipating cold. Finally, the key targets for treating pneumoconiosis are screened out, providing an important basis for the development of therapeutic drugs for it.
6.Methodological Problems and Solutions Commonly Encountered in Scientific Reviews of Investor Initiated Trial in the Field of Traditional Chinese Medicine
Fang HAN ; Jia XU ; Baoli LIU ; Qingquan LIU ; Bin LI ; Jing HU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(6):1509-1513
The number of investor initiated trial(IIT)in the field of traditional Chinese medicine(TCM)in China has been increasing year by year,but there are still many problems about their scientific validity.Scientific review is the top priority of IIT management,which is of great significance to improve the quality of IIT.Considering the characteristics of IIT in the field of TCM,randomized controlled trials and discuss common methodological problems in the scientific review process of IIT are focused on,such as non-standard placebo setting,unclear research hypothesis or improper selection of hypothesis test type,inappropriate sample size estimation methods,insufficient characteristics of TCM in outcome measures,unreasonable statistical analysis methods,etc.At the same time,corresponding solutions are proposed to increase the scientific and credibility of IIT,thus improving the research quality of IIT in TCM.
7.The Problems and Solutions in the Design and Record of TCM Clinical Research Case Report Form
Fang HAN ; Kegang CAO ; Ying GAO ; Baoli LIU ; Tiantian ZHOU ; Jing HU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):533-538
Case report form(CRF)is an important tool to obtain clinical research data.Scientifically designed and properly recorded CRF is of great significance to improve the quality of clinical research.The author summarized the common problems existing in the design and recording of CRF in traditional Chinese medicine(TCM)clinical studies,including:①Delayed design time point.②Unstandardized CRF design,recording and modification.③Imperfect records of combined medication/therapy.④Insufficient quantification of syndrome efficacy indicators and objectification of tongue and pulse.⑤ Insufficient protection of subjects' privacy.⑥ Unstandardized records of adverse events.Accordingly,this paper discusses some solutions to provide reference for other TCM researchers,including:①Advance CRF design time.②Standardize CRF design,recording and modification.③Design drug combinations/therapies according to Clinical Data Acquisition Standards Harmonization(CDASH).④Standardization of syndrome and tongue and pulse.⑤Use of subject identification codes to protect privacy.⑥AE records should vary from study to study.
8.Application of PDCA Cycle in the Mid-Term Inspection of Scientific Research Projects
Fang HAN ; Baoli LIU ; Guangzhong ZHANG ; Qingquan LIU ; Guowang YANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):868-872
Discipline construction is the power source to realize the high quality development of public hospitals,and high quality scientific research management is the inevitable path to realize the connotative development of public hospitals.The quality improvement of scientific research project process management is step-by-step,and mid-term inspection is a representative work.This paper applies PDCA cycle theory to the mid-term inspection of scientific research projects,analyzes the problems encountered in the mid-term inspection of scientific research projects from the four stages of plan,implementation,check and act,and develops effective intervention measures.The mid-term inspection mode,which combines publicity activities of scientific research norms with self-examination by researchers and on-the-spot inspection by the scientific research department,should be carried out to standardize the process of mid-term inspection of scientific research projects and promote the high-quality development of scientific research in hospitals.
9.Management and optimization of the hospital scientific research approval process based on the DingTalk platform
Jie FAN ; Yang ZHENG ; Baoli LIU ; Wei HAN ; Mifeng LIU
Chinese Journal of Medical Science Research Management 2023;36(2):156-160
Objective:In order to reduce the transactional burden of scientific researchers and ensure the researchers concentrate on their scientific research, the hospital implemented the whole-process management and optimization of the scientific research approval process based on the DingTalk platform to improve the efficiency of scientific research.Methods:We sorted out the list of routine work in the implementation of scientific research projects and analyzed the key points affecting the efficiency of scientific research management, specifically the processes of reimbursement of scientific research funds, budget adjustment, paper submission approval, and research drug application, then we developed corresponding modules on the DingTalk platform.Results:In 2021, the hospital approved 3 214 scientific research funding reimbursements, including 1 917 approvals below 5 000 yuan, with a median approval time of 19 (5~28) hours, 1 297 approvals above 5 000 yuan, with a median approval time of 26 (10~50) hours. In addition, 17 budget adjustments, 456 paper submissions, and 31 research drug applications were approved on the DingTalk platform, resulting in a smooth overall approval process, saving the time costs of medical staff and improving work efficiency.Conclusions:The scientific research approval management based on this platform realizes the concept of refined management, which can meet the needs of the normalization of epidemic prevention and control and effectively promote the high-quality development of hospital scientific research management.
10.Analysis of active surveillance results of pneumoconiosis in Jiangsu Province in 2019
Xiaoyu WANG ; Baoli ZHU ; Lei HAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(12):927-931
Objective:To conduct active surveillance of pneumoconiosis in Jiangsu Province in 2019, to understand the status quo of occupational health of dust-exposed workers, timely detect occupational health damage and occupational hazard factors, and provide scientific basis for the prevention and control of pneumoconiosis in the future.Methods:From January to December 2019, counties (cities and districts) with relatively concentrated dust hazard enterprises in Jiangsu Province were selected as monitoring points to carry out active surveillance of pneumoconiosis, and occupational health examination of dust workers (3540 people) in 255 enterprises were carried out, including chest radiographs and lung function examinations. SPSS 26.0 statistical software was used for statistical analysis of the data, and Chi-square test was used to analyze the difference level of the rate between different groups such as gender, age and service.Results:Among the 255 employers, small enterprises accounted for the highest proportion (186 enterprises, 72.94%), private economy accounted for the highest proportion (225 enterprises, 88.24%), and machinery manufacturing industry accounted for the highest proportion (44 enterprises, 17.25%). Among the 3540 workers exposed to dust, 6 suspected occupational diseases (0.17%), 50 occupational contraindications (1.41%), and 1469 other diseases or abnormalities (41.50%) were detected. Among the 3540 workers exposed to dust, 399 (11.27%) had abnormal chest radiography results, and 848 (23.95%) had abnormal lung function indicators. The abnormal detection rate of chest radiographs in males (12.25%, 359/2931) was higher than that in females (6.57%, 40/609), and the abnormal detection rate of lung function in females (32.18%, 196/609) was higher than that in males (22.24%, 652/2931), with statistical significance ( P<0.05). The age of the workers exposed to dust ranged from 17 to 75 (41.78±10.39) years old, and the years of service in contact with dust of the workers ranged from 0.08 to 42 (6.72±7.47) years. There were statistically significant differences in the detection rate of abnormal chest radiography and abnormal lung function among different age and seniority workers ( P<0.05). The abnormal rates of forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1) and FEV 1/FVC were 13.79% (488/3540), 15.28% (541/3540) and 1.86% (66/3540), respectively. There were significant differences in the detection rate of abnormal chest radiography and abnormal lung function among workers exposed to different dust types ( P<0.05) . Conclusion:There are few suspected occupational diseases detected by active surveillance of pneumoconiosis in Jiangsu Province in 2019, and there are differences in occupational health examination results among workers with different dust types, ages, genders and dust exposure years.

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