1.Mechanism of Jianfu mixture in the treatment of erectile dysfunction based on network pharmacology analysis, molecular docking and in vitro experimental validation
Yantao YANG ; Chao YU ; Zhihang ZHANG ; Yujiong PAN ; Xiaofeng HE ; Min XU
Journal of Pharmaceutical Practice and Service 2026;44(6):296-305
Objective To explore the molecular mechanism of Jianfu mixture in the treatment of erectile dysfunction (ED) by network pharmacology and molecular docking techniques, and validate its core targets and mechanisms through in vitro experiments. Methods The active components and corresponding molecular targets of Jianfu mixture were searched by searching TCMSP and Batman-TCM databases, and the disease targets of ED were searched by using GeneCards database. Find the intersection of drug ingredient target and disease target. The interaction between intersected targets was described and analyzed by String database, and the analysis results were visualized by Cytoscape software to determine the core target and the corresponding active components. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for intersection targets; the core target within the intersection were found through MCODE plug-in on Cytoscape software and molecular docking was performed with the corresponding active ingredients. An endothelial dysfunction model was established by transfecting HUVECs with si-eNOS. Intervene with different concentrations of the Jianfu mixture for the model cells for 24 h. QPCR was used to detect mRNA expression of core targets (MAPK1, MAPK3, JUN, ESR1, MAPK8); Western blot was used to analyze protein expression (eNOS, JUN, p-JUN, MAPK, p-MAPK) and phosphorylation levels. Results 144 effective active components and 168 active components target-disease targe intersection of Jianfu mixture were obtained. GO analysis revealed 200 5 biological processes, 151 molecular functions, and 63 cellular components. KEGG analysis yielded 181 pathways. 5 core targets including MAPK1, MAPK3, JUN, ESR1 and MAPK8 were screened out. The active components such as β-sitosterol, kaempferol, astapterocarpan had good binding affinity with the core target. In vitro experiments confirmed successful construction of the endothelial dysfunction model (eNOS expression significantly decreased after si-eNOS transfection). Jianfu mixture dose-dependently inhibited mRNA expression of MAPK1, MAPK3, JUN, ESR1, and MAPK8. Additionally, it reduced phosphorylation levels of JUN and MAPK, indicating inhibition of the JNK/c-Jun and ERK/MAPK signaling pathways to improve endothelial function. Conclusion Jianfu mixture treats ED by suppressing abnormal activation of multi-target signaling pathways (MAPK/JUN/ESR1), reducing endothelial apoptosis, and promoting NO synthesis. This mechanism aligns with the traditional Chinese medicine principle of “activating blood circulation, resolving stasis, tonifying Qi, and strengthening cardiovascular function.” The study provided molecular-level evidence for the therapeutic efficacy of Jianfu mixture in ED management.
2.Mechanism of Jianfu mixture in the treatment of erectile dysfunction based on network pharmacology analysis, molecular docking and in vitro experimental validation
Yantao YANG ; Chao YU ; Zhihang ZHANG ; Yujiong PAN ; Xiaofeng HE ; Min XU
Journal of Pharmaceutical Practice and Service 2026;44(6):296-305
Objective To explore the molecular mechanism of Jianfu mixture in the treatment of erectile dysfunction (ED) by network pharmacology and molecular docking techniques, and validate its core targets and mechanisms through in vitro experiments. Methods The active components and corresponding molecular targets of Jianfu mixture were searched by searching TCMSP and Batman-TCM databases, and the disease targets of ED were searched by using GeneCards database. Find the intersection of drug ingredient target and disease target. The interaction between intersected targets was described and analyzed by String database, and the analysis results were visualized by Cytoscape software to determine the core target and the corresponding active components. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for intersection targets; the core target within the intersection were found through MCODE plug-in on Cytoscape software and molecular docking was performed with the corresponding active ingredients. An endothelial dysfunction model was established by transfecting HUVECs with si-eNOS. Intervene with different concentrations of the Jianfu mixture for the model cells for 24 h. QPCR was used to detect mRNA expression of core targets (MAPK1, MAPK3, JUN, ESR1, MAPK8); Western blot was used to analyze protein expression (eNOS, JUN, p-JUN, MAPK, p-MAPK) and phosphorylation levels. Results 144 effective active components and 168 active components target-disease targe intersection of Jianfu mixture were obtained. GO analysis revealed 200 5 biological processes, 151 molecular functions, and 63 cellular components. KEGG analysis yielded 181 pathways. 5 core targets including MAPK1, MAPK3, JUN, ESR1 and MAPK8 were screened out. The active components such as β-sitosterol, kaempferol, astapterocarpan had good binding affinity with the core target. In vitro experiments confirmed successful construction of the endothelial dysfunction model (eNOS expression significantly decreased after si-eNOS transfection). Jianfu mixture dose-dependently inhibited mRNA expression of MAPK1, MAPK3, JUN, ESR1, and MAPK8. Additionally, it reduced phosphorylation levels of JUN and MAPK, indicating inhibition of the JNK/c-Jun and ERK/MAPK signaling pathways to improve endothelial function. Conclusion Jianfu mixture treats ED by suppressing abnormal activation of multi-target signaling pathways (MAPK/JUN/ESR1), reducing endothelial apoptosis, and promoting NO synthesis. This mechanism aligns with the traditional Chinese medicine principle of “activating blood circulation, resolving stasis, tonifying Qi, and strengthening cardiovascular function.” The study provided molecular-level evidence for the therapeutic efficacy of Jianfu mixture in ED management.
3.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
4.Characterization and Application of Moisture Absorption Kinetics of Traditional Chinese Medicines Based on Double Exponential Model:A Review
Yanting YU ; Lei XIONG ; Yan HE ; Wei LIU ; Jing YANG ; Yao ZHANG ; Jiali CHEN ; Xiaojian LUO ; Xiaoyong RAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):340-346
Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica(CMM). Elucidating hygroscopic mechanisms plays a vital role in formulation design, process optimization, and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms, with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion, tailored to the physical properties of CMM extracts. In recent years, this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties, offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM, analyzes its advantages, disadvantages, and challenges in this domain, and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies, while also offering insights for its broader application in food and polymer materials.
5.The Neural Circuit Characteristics of Repetitive Transcranial Magnetic Stimulation Over The Dorsolateral Prefrontal Cortex for The Treatment of Migraine
Chen-Xia JIN ; Bo-Lin TAN ; Yang YE ; Ji-Qing HE ; Ling-Yan WANG ; Zhong-Ming GAO ; Yu-Jun WANG ; Hui-Li LIU ; Yong-Xing YAN ; Xian-Wei CHE
Progress in Biochemistry and Biophysics 2026;53(7):1953-1968
ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.
6.Prevention and Treatment Strategies for Chronic Atrophic Gastritis Based on Theory of Vigorous Fire Consuming Qi and ROS/NLRP3-mediated Inflammation-mitochondrial Damage Axis
Yu SHEN ; Shijin LIN ; Sihan LI ; Minghan HUANG ; Jingyao SHI ; Zeyu ZHENG ; Chunbo YANG ; Youcheng HE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):287-295
Chronic atrophic gastritis (CAG), a premalignant gastric condition, represents a critical stage in inflammation-cancer transformation. In this pathological process, mitochondrial damage serves as a key mediator in the inflammation-driven transformation of normal gastric mucosal epithelial cells into gastric cancer cells, while the dysregulation of the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3) axis plays a key role in perpetuating the vicious cycle of inflammation-mitochondrial damage. The classical theory of traditional Chinese medicine (TCM), vigorous fire consuming Qi, aptly encapsulates this pathological feature. The essence of this theory lies in the struggle between pathogenic and vital factors, wherein vigorous fire shares similarities with chronic inflammation and may be regarded as a driving force behind inflammation-cancer transformation. Qi reflects the mitochondrial function, and consuming Qi signifies structural and functional impairment of mitochondria. Thus, this theory accurately summarizes the pathological characteristics of inflammation-mitochondrial damage during CAG progression. Building upon this theoretical framework, the theory of vigorous fire consuming Qi provides a holistic understanding of CAG pathogenesis. Reviewing the clinical expertise of TCM master YANG Chunbo in treating spleen-stomach disorders, this paper further elucidates its therapeutic implications: modulating systemic inflammatory responses to restore gastric mucosal homeostasis and targeting mitochondrial damage as a pivotal intervention to delay CAG progression. Clinically, achieving dynamic equilibrium between fire and Qi is essential, mitigating excessive inflammation without compromising vital Qi, while reinforcing Qi without exacerbating pathological fire. This approach offers novel insights for developing preventive and therapeutic strategies against CAG.
7.Construction and Validation of Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Carotid Artery Plaques in 3 009 Individuals with High-risk of Stroke
Shuqi QIN ; Xiangyu GUO ; Weihao YANG ; Yang CHEN ; Ying YU ; Limin HE ; Jialin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):242-250
ObjectiveTo construct a risk prediction model for carotid artery plaques in high-risk populations of stroke based on five machine learning methods. MethodsThe clinical information of the high-risk population of stroke was collected. Factor analysis and statistical analysis of syndrome elements were conducted on their traditional Chinese medicine (TCM) symptoms and tongue and pulse manifestations. On the basis of the results of factor analysis and variable screening, five machine learning methods-classification and regression tree (CART) decision tree, support vector machine (SVM), back propagation(BP) neural network, logistic regression, and random forest-were used to construct the risk prediction model for carotid artery plaques. ResultsThe most common TCM syndrome elements in the high-risk population of stroke was Qi deficiency. The scores of Qi deficiency, Yin deficiency, and Yang deficiency in the population with carotid artery plaques were higher than those without carotid artery plaques (P<0.05). The CART decision tree, SVM, logistic regression, BP neural network, and random forest models showed the areas under the receiver operating characteristic (ROC) curves of 0.71, 0.75, 0.76, 0.76, and 0.75, the accuracy rates of 68.94%, 69.27%, 69.44%, 70.10%, and 69.60%, the precision rates of 68.56%, 68.53%, 68.75%, 69.74%, and 69.42%, the recall rates of 68.91%, 67.93%, 67.92%, 68.10%, and 67.31%, and the F1 values of 0.69, 0.68, 0.68, 0.68, and 0.68, respectively. ConclusionAmong the high-risk population of stroke, the most frequently distributed TCM syndrome element is Qi deficiency, with the rest mainly being fire heat, Yin deficiency, Yang deficiency, phlegm dampness, blood stasis, and Qi stagnation. Deficiency syndrome may be a major factor leading to carotid artery plaques in the high-risk population of stroke. The BP neural network model demonstrates better performance in predicting the risk of carotid artery plaques in the high-risk population of stroke. People with carotid artery plaques are more likely to present with symptoms such as a heavy head, dizziness, headache, and thready pulse. The primary community benefits more widely when the BP neural network model is adopted to predict the risk of carotid artery plaques in the high-risk population of stroke over 40 years old.
8.Construction and Validation of Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Carotid Artery Plaques in 3 009 Individuals with High-risk of Stroke
Shuqi QIN ; Xiangyu GUO ; Weihao YANG ; Yang CHEN ; Ying YU ; Limin HE ; Jialin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):242-250
ObjectiveTo construct a risk prediction model for carotid artery plaques in high-risk populations of stroke based on five machine learning methods. MethodsThe clinical information of the high-risk population of stroke was collected. Factor analysis and statistical analysis of syndrome elements were conducted on their traditional Chinese medicine (TCM) symptoms and tongue and pulse manifestations. On the basis of the results of factor analysis and variable screening, five machine learning methods-classification and regression tree (CART) decision tree, support vector machine (SVM), back propagation(BP) neural network, logistic regression, and random forest-were used to construct the risk prediction model for carotid artery plaques. ResultsThe most common TCM syndrome elements in the high-risk population of stroke was Qi deficiency. The scores of Qi deficiency, Yin deficiency, and Yang deficiency in the population with carotid artery plaques were higher than those without carotid artery plaques (P<0.05). The CART decision tree, SVM, logistic regression, BP neural network, and random forest models showed the areas under the receiver operating characteristic (ROC) curves of 0.71, 0.75, 0.76, 0.76, and 0.75, the accuracy rates of 68.94%, 69.27%, 69.44%, 70.10%, and 69.60%, the precision rates of 68.56%, 68.53%, 68.75%, 69.74%, and 69.42%, the recall rates of 68.91%, 67.93%, 67.92%, 68.10%, and 67.31%, and the F1 values of 0.69, 0.68, 0.68, 0.68, and 0.68, respectively. ConclusionAmong the high-risk population of stroke, the most frequently distributed TCM syndrome element is Qi deficiency, with the rest mainly being fire heat, Yin deficiency, Yang deficiency, phlegm dampness, blood stasis, and Qi stagnation. Deficiency syndrome may be a major factor leading to carotid artery plaques in the high-risk population of stroke. The BP neural network model demonstrates better performance in predicting the risk of carotid artery plaques in the high-risk population of stroke. People with carotid artery plaques are more likely to present with symptoms such as a heavy head, dizziness, headache, and thready pulse. The primary community benefits more widely when the BP neural network model is adopted to predict the risk of carotid artery plaques in the high-risk population of stroke over 40 years old.
9.Relationship between self-management behaviors and time perspective among patients with comorbid diabetes
YU Dandan ; ZHANG Yaping ; XU Huilin ; HE Dandan ; LIANG Tongtong ; YANG Jiali ; LI Jun
Journal of Preventive Medicine 2025;37(2):130-134
Objective:
To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes.
Methods:
The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model.
Results:
A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915).
Conclusion
The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.
10.Application of "balance-shaped sternal elevation device" in the subxiphoid uniportal video-assisted thoracoscopic surgery for anterior mediastinal masses resection
Jinlan ZHAO ; Weiyang CHEN ; Chunmei HE ; Yu XIONG ; Lei WANG ; Jie LI ; Lin LIN ; Yushang YANG ; Lin MA ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):308-312
Objective To introduce an innovative technique, the "balance-shaped sternal elevation device" and its application in the subxiphoid uniportal video-assisted thoracoscopic surgery (VATS) for anterior mediastinal masses resection. Methods Patients who underwent single-port thoracoscopic assisted anterior mediastinal tumor resection through the xiphoid process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from May to June 2024 were included, and their clinical data were analyzed. Results A total of 7 patients were included, with 3 males and 4 females, aged 28-72 years. The diameter of the tumor was 1.9-17.0 cm. The operation time was 62-308 min, intraoperative blood loss was 5-100 mL, postoperative chest drainage tube retention time was 0-9 days, pain score on the 7th day after surgery was 0-2 points, and postoperative hospital stay was 3-12 days. All patients underwent successful and complete resection of the masses and thymus, with favorable postoperative recovery. Conclusion The "balance-shaped sternal elevation device" effectively expands the retrosternal space, providing surgeons with satisfactory surgical views and operating space. This technique significantly enhances the efficacy and safety of minimally invasive surgery for anterior mediastinal masses, reduces trauma and postoperative pain, and accelerates patient recovery, demonstrating important clinical significance and application value.


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