1.Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
Yi-fan LIU ; Meng LI ; De-yu CUI ; Xiao-yan LU ; Ting-bo NING ; Chun-xiu XU ; Jing-chun YAO ; Ji-dong ZHOU ; Zhong LIU
Chinese Pharmacological Bulletin 2025;41(8):1453-1462
Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.
2.Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.
Xiang-Yu SONG ; Yang-Hui DONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Yan-Jun GUAN ; Bo-Yao YANG ; Si-Ce WANG ; Sheng-Feng CHEN ; Peng-Kai LI ; Heng CHEN ; Hao-Chen ZUO ; Zhan-Cheng YANG ; Wen-Jing XU ; Ya-Qun ZHAO ; Jiang PENG
Chinese Journal of Traumatology 2025;28(6):469-476
PURPOSE:
To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss.
METHODS:
This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA+, K+, and Ca2+ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance.
RESULTS:
The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA+ and K+ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca2+ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group.
CONCLUSIONS
Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals
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Perfusion/methods*
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Disease Models, Animal
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Brain Injuries/etiology*
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Swine
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Male
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Hypothermia, Induced/methods*
3.Mechanism of silibinin derivative Sil-1 modulating MAPK signaling pathway to inhibit acute myocardial infarction in rats
Yi-fan LIU ; Meng LI ; De-yu CUI ; Xiao-yan LU ; Ting-bo NING ; Chun-xiu XU ; Jing-chun YAO ; Ji-dong ZHOU ; Zhong LIU
Chinese Pharmacological Bulletin 2025;41(8):1453-1462
Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.
4.Mechanism of action of a novel IDO1 inhibitor and icartin combination on diabetic nephropathy based on intestinal flora combined with metabolomics
Meng LI ; De-yu CUI ; Yi-fan LIU ; Yan XU ; Meng-meng SHEN ; Xiao-yan LU ; Jing-chun YAO
Chinese Pharmacological Bulletin 2025;41(3):528-537
Aim To study the protective effect of a combination of IDO-1 inhibitor(3-047)with Icartin(Y003)at a mass ratio of 1∶1.6 on diabetic nephrop-athy in db/db mice and its mechanism of action.Methods After 24 weeks of treatment in db/db mice,on the basis of pharmacodynamic evaluation,16S rD-NA gene sequencing combined with untargeted metabo-lomics was used to further investigate the mechanism of improvement of diabetic nephropathy from the perspec-tive of the"microbial-intestinal-nephrotic"axis by the combination of 3-047 and Y003.Results Compared with the control group,mice in the model group showed significantly higher levels of FBG,Scr,BUN,TC,TG,LDL-C,lower levels of HDL-C(P<0.05),significantly increased urinary albumin excretion rate,thickening of the glomerular basement membrane and dilatation of the tunica albuginea,aggravation of oxida-tive stress damage,lower abundance,structural and functional disorders of the intestinal flora.The combi-nation of 3-047 and Y003 could improve the above conditions to different degrees,significantly increase the relative abundance of Alloprevotella,Alistipes and Dubosiella,and decrease the relative abundance of Ligilactobacillus,Dubosiella and Lactococcus.A total of 11 biomarkers with significant differences were screened by metabolomics and enriched to the pathways of alanine,tyrosine and tryptophan biosynthesis,and unsaturated fatty acid biosynthesis.Conclusions The combination of 3-047 and Y003 could improve the dis-orders of glucose-lipid metabolism,reduce the structur-al and functional damage of renal tissues,and alleviate oxidative stress by regulating the intestinal flora and re-lated amino acid metabolism,and thus achieve a pro-tective effect on mice with diabetic nephropathy,dem-onstrating that the intestinal flora and the related me-tabolites are potential targets for the treatment of dia-betic nephropathy.
5.Dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders
Jing DING ; Ying CHEN ; Xiaohua CUI ; Zhuocheng MENG ; Suo ZHANG ; Jiao HE ; Yuanyuan ZHAI
Chinese Journal of Neuromedicine 2025;24(11):1125-1133
Objective:To explore differences in dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders based on therapeutic drug monitoring data.Methods:A retrospective analysis was performed; clinical data, including demographic characteristics, therapeutic drug monitoring results, comorbidities, medication details (daily valproic acid dose, concomitant medications), and liver and kidney function indicators, were collected from 633 patients with bipolar disorder or schizophrenia who were hospitalized at Xi'an Mental Health Center and received different valproates from January 2024 to June 2024 (98 patients receiving sodium valproate and 535 receiving magnesium valproate). Clinical data between a sodium valproate group and a magnesium valproate group were compared. Multivariate linear regression was used to identify independent influencing factors for dose-adjusted plasma concentration of valproic acid. Valproic acid daily doses, and plasma concentrations and dose-adjusted plasma concentrations of valproic acid were compared between the two groups, with subgroup analyses conducted by gender and age categories.Results:A total of 658 measurements of plasma valproic acid concentration were obtained in 633 patients, including 104 measurements in the sodium valproate group and 554 in the magnesium valproate group. Significant differences in proportions of comorbidities and concomitant use of olanzapine, quetiapine and clozapine were observed between the sodium valproate group and magnesium valproate group ( P<0.05). After adjusting for age, gender, body mass index, comorbidities, concomitant medications, and liver and kidney function indicators, the type of valproates remained an independent influencing factor for dose-adjusted plasma concentration of valproic acid (adjusted unstandardized B coefficient=13.814, 95% CI: 8.090-19.540, P<0.001). Daily dose in the sodium valproate group (1.0[1.0, 1.0] g/d) was significantly higher than that in the magnesium valproate group (0.5[0.5, 1.0] g/d), and dose-adjusted plasma concentration of valproic acid in the magnesium valproate group (93.00 [75.60, 117.40] [μg/mL]/[g·d]) was statistically higher than that in the sodium valproate group (78.55 [57.90, 90.00][μg/mL]/[g·d], P<0.05). Subgroup analysis revealed that, among patients stratified by genders and ages (<40 years vs. ≥40 years), the daily dose in the sodium valproate group was significantly higher than that in the magnesium valproate group, while the dose-adjusted plasma concentration of valproic acid in the magnesium valproate group was significantly higher than that in the sodium valproate group ( P<0.05). Conclusion:Significant differences in dose-adjusted plasma concentrations of valproic acid are observed among different valproate formulations for the treatment of mental disorders; therefore, therapeutic drug monitoring should be performed in patients when switching valproates to facilitate precise individualized dosage adjustment.
6.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.
7.Development and application on a full process disease diagnosis and treatment assistance system based on generative artificial intelligence.
Wanjie YANG ; Hao FU ; Xiangfei MENG ; Changsong LI ; Ce YU ; Xinting ZHAO ; Weifeng LI ; Wei ZHAO ; Qi WU ; Zheng CHEN ; Chao CUI ; Song GAO ; Zhen WAN ; Jing HAN ; Weikang ZHAO ; Dong HAN ; Zhongzhuo JIANG ; Weirong XING ; Mou YANG ; Xuan MIAO ; Haibai SUN ; Zhiheng XING ; Junquan ZHANG ; Lixia SHI ; Li ZHANG
Chinese Critical Care Medicine 2025;37(5):477-483
The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence
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Humans
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Delivery of Health Care
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Generative Artificial Intelligence
8.Survey of genetic diversity of select tick species in Inner Mongolia
Meng-yu CUI ; Si SU ; Lan MU ; Rui-juan GAO ; Qi-qi GUO ; Hong REN ; Li-li BAO ; Jing-feng YU
Chinese Journal of Zoonoses 2025;41(2):171-177
The aim of this study was to understand the internal genetic diversity and population history dynamics of ticks in Inner Mongolia,to provide data for designing effective vector control programs and revealing ticks'transmission mechanisms.From 2022 to 2023,the manual collection method was used to collect samples in Inner Mongolia.The 16S rDNA and COI gene sequences of ticks were used to identify Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus,and analyze the sequence characteristics and genetic diversity within the populations.Base composition analysis indicated that the average A+T content of the 16S rDNA gene and CO I gene in the three ticks was significantly higher than that of C+G.Moreover,22 haplotypes of the COI gene and 12 haplotypes of the 16S rDNA sequence were identified in Hyalomma marginatum.Eleven haplotypes were identified according to the COI gene,and nine haplotypes were identified according to the16S rDNA sequence of Haemaphysalis concinna.Two haplotypes were identified on the basis of the COI gene,and six haplotypes were identified on the basis of the 16S rDNA sequence of Ar gas persicus.The minimum 16S rDNA haplotype diversity was 0.264 for Ar gas persicus and 0.579 for the other two species.The nucleotide diversity of the three tick species was less than 0.05.Tajima's val-ue and Fu's Fs value of the neutrality test were negative.Base saturation substitution analysis indicated that neither of the two genes in the three tick species reached saturation.The phylogenetic tree revealed that Hyalomma marginatum,Haema physalis concinna,and Ar gas persicus in Inner Mongolia independently aggregated into branches.In conclusion,the base content of Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus genes in Inner Mongolia was consist-ent with the characteristics of insect mitochondrial DNA content.Furthermore,the three tick populations showed rapid evolu-tionary population expansion,and the phylogeny of three tick species showed independent aggregation into clades,with no pop-ulation isolation.
9.Study on the influencing factors of selection and price decline in the centralized volume-based purchase of Proprietary Chinese Medicine:Taking Hubei Province as an example
Shu-han AN ; Jing XIANG ; Meng-na CAI ; Dan CUI
Chinese Journal of Health Policy 2025;18(3):74-80
Objective:Analyse the factors affecting whether the first two batches of centralized volume-based purchase of Proprietary Chinese Medicine were selected,the price difference and the rate of reduction,so as to provide a basis for improving the policy of centralized volume-based purchase of Proprietary Chinese Medicine.Methods:The first two batches of centralized volume-based purchase of Proprietary Chinese Medicine were selected for the study.Logistic regression was used to analyse the influencing factors of whether the selection was won or not.Multiple linear regression was used to analyse the influencing factors of price difference/reduction after being selected.Results:Proprietary Chinese Medicine with a high degree of acceptance by medical institutions and belonging to the category of essential medicines have a higher probability of being selected.The probability of selected products in the first batch of centralised purchase is greater for enterprises with a market share of more than 50%.In the first batch of centralized volume-based purchase of Proprietary Chinese Medicine,the price difference of injections and medicines belonging to the catalogue of essential medicines is greater.Price reductions were greater for those with low market share,low recognition by medical institutions,and a large number of enterprises in the A-competition unit and the same competition unit.In the second batch of centralised volume-based purchase of Proprietary Chinese Medicine,the price difference is greater for injections,and those with qualifications for the production of Chinese herbal medicines.the price reduction is greater in the B competitive unit.Conclusion:The centralized volume-based purchase of Proprietary Chinese Medicine has been both'quality-assured'and'price-reduced'.The centralized volume-based purchase of Proprietary Chinese Medicine has been gradually improved,and the tilt towards large enterprises has been reduced,so that the centralized volume-based purchase of Proprietary Chinese Medicine can achieve a'bottom price'.However,it is still necessary to start from the quality of identification,fair competition,and so on,and the centralized volume-based purchase of Proprietary Chinese Medicine fully linked to promote the centralized purchase of Traditional Chinese Medicine Decoction Pieces to a stable and far-reaching.
10.Relationship between decision-making preparation and facilitation of patient involvement in outpatient hypertension patients: based on latent profile model
Jingyuan JI ; Junhui XU ; Meng CUI ; Yuankun ZHOU ; Yan ZHANG ; Chun MU ; Yi HE ; Hui LIU ; Jing MA
Chinese Journal of Practical Nursing 2025;41(18):1417-1426
Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.

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