1.Liuwei Dihuangwan Promote Mitophagy to Modulate Neuroinflammation and Behavioral Impairments in Rat Model of Autism Spectrum Disorder (ASD)
Pengjue HUANG ; Mingyue JIANG ; Ji WU ; Niya YIN ; Lei OUYANG ; Qinquan ZHU ; Di ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):52-60
ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder (ASD) and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid (VPA) (10 rats) or normal saline (2 rats), and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model, low-dose (0.75 g·kg-1) and high-dose (1.5 g·kg-1) Liuwei Dihuangwan, vitamin D (positive drug, 3.7×10-5 g·kg-1), and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention, the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining (HE) was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 (Iba-1) in the prefrontal tissue. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), adenosine monophosphate-activated protein kinase (AMPK), phosphorylated Unc-51-like autophagy-activating kinase 1 (p-ULK1), Unc-51-like autophagy-activating kinase 1 (ULK1), and FUN14 domain-containing protein 1 (FUNDC1). ResultsCompared with the blank group, the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test (P<0.01) and showed reductions in the total distance traveled, average speed, distance traveled in the central area, and time spent in the central area in the open field test (P<0.01). In addition, the model group showed extensive apoptosis of neurons, with shrunken nuclei and red-stained cytoplasm, and extensive necrosis of neurons in the prefrontal tissue, mitochondrial swelling, decreased matrix density, disrupted cristae, and autophagic lysosomes in neurons, increases in the rate of Iba-1 positive cells in the prefrontal area (P<0.01) and the levels of TNF-α and IL-6 (P<0.01), and down-regulation in the expression of p-AMPK/AMPK, p-ULK1/ULK1, and FUNDC1 (P<0.01). Compared with the model group, low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test (P<0.05, P<0.01), increased the total distance traveled, average speed, distance traveled in the central area, and time spent in the central area in the open field test (P<0.05, P<0.01), restored the morphology of neurons in the prefrontal tissue, decreased the number of apoptotic cells, alleviated the swelling of mitochondria in neurons, increased the matrix density, mitigated the fragmentation and disorder of cristae, and increased the number of autophagosomes. Moreover, the drugs decreased the rate of Iba-1 positive cells in the prefrontal area (P<0.01), lowered the levels of TNF-α and IL-6 (P<0.01), and up-regulated the expression of p-AMPK/AMPK, p-ULK1/ULK1, and FUNDC1 (P<0.01). ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.
2.Mechanisms of Shenqi Wenfei Prescription in Intervening in Chronic Obstructive Pulmonary Disease in Rats Based on ROS/TXNIP/NLRP3 Signaling Pathway
Di WU ; Mengyao SHI ; Lu ZHANG ; Tong LIU ; Jiabing TONG ; Cheng YANG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):78-87
ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription (SQWF) on chronic obstructive pulmonary disease (COPD). MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide (LPS) combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group, a model group, low-, medium-, and high-dose SQWF groups (2.835, 5.67, 11.34 g·kg-1), and a Yupingfeng group (1.35 g·kg-1). Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed, and the lung function in each group was assessed. Hematoxylin-eosin (HE) staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The release level of lactate dehydrogenase (LDH) in BALF was detected by a microplate assay. Reactive oxygen species (ROS) levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde (MDA), total superoxide dismutase (SOD), and reduced glutathione (GSH) in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein (TXNIP) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), Caspase-1 p20, gasdermin D (GSDMD), GSDMD N-terminal active fragment (GSDMD-N), interleukin-1β (IL-1β), and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group, the model group showed lassitude, fatigue, tachypnea, and audible phlegm sounds, and lung function significantly declined (P0.01). Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly (P0.05). The number of TUNEL-positive cells increased (P0.01). Levels of LDH, ROS, and MDA in BALF increased significantly (P0.01), while GSH and SOD activities decreased significantly (P0.01). Lung tissue cells showed irregular morphology, swollen mitochondria, disrupted cell membranes, and abundant vesicles, i.e., pyroptotic bodies. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue were significantly elevated (P0.01), and serum IL-1β and IL-18 levels also increased significantly (P0.01). Compared with the model group, each medication group showed alleviation of qi deficiency symptoms and improved lung function (P0.01). Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased (P0.05). The number of TUNEL-positive cells decreased significantly (P0.01). Levels of LDH, ROS, and MDA decreased significantly (P0.05), while GSH and SOD activities significantly increased (P0.01). Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue significantly decreased (P0.01), and serum IL-1β and IL-18 levels also decreased significantly (P0.05). ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.
3.Mechanisms of Shenqi Wenfei Prescription in Intervening in Chronic Obstructive Pulmonary Disease in Rats Based on ROS/TXNIP/NLRP3 Signaling Pathway
Di WU ; Mengyao SHI ; Lu ZHANG ; Tong LIU ; Jiabing TONG ; Cheng YANG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):78-87
ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription (SQWF) on chronic obstructive pulmonary disease (COPD). MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide (LPS) combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group, a model group, low-, medium-, and high-dose SQWF groups (2.835, 5.67, 11.34 g·kg-1), and a Yupingfeng group (1.35 g·kg-1). Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed, and the lung function in each group was assessed. Hematoxylin-eosin (HE) staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The release level of lactate dehydrogenase (LDH) in BALF was detected by a microplate assay. Reactive oxygen species (ROS) levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde (MDA), total superoxide dismutase (SOD), and reduced glutathione (GSH) in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein (TXNIP) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), Caspase-1 p20, gasdermin D (GSDMD), GSDMD N-terminal active fragment (GSDMD-N), interleukin-1β (IL-1β), and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group, the model group showed lassitude, fatigue, tachypnea, and audible phlegm sounds, and lung function significantly declined (P0.01). Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly (P0.05). The number of TUNEL-positive cells increased (P0.01). Levels of LDH, ROS, and MDA in BALF increased significantly (P0.01), while GSH and SOD activities decreased significantly (P0.01). Lung tissue cells showed irregular morphology, swollen mitochondria, disrupted cell membranes, and abundant vesicles, i.e., pyroptotic bodies. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue were significantly elevated (P0.01), and serum IL-1β and IL-18 levels also increased significantly (P0.01). Compared with the model group, each medication group showed alleviation of qi deficiency symptoms and improved lung function (P0.01). Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased (P0.05). The number of TUNEL-positive cells decreased significantly (P0.01). Levels of LDH, ROS, and MDA decreased significantly (P0.05), while GSH and SOD activities significantly increased (P0.01). Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue significantly decreased (P0.01), and serum IL-1β and IL-18 levels also decreased significantly (P0.05). ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.
4.Herbal Textual Research on Malvae Semen in Famous Classical Formulas
Dongxue CHEN ; Yibo LIU ; Yangyang YU ; Guoshuai LYU ; Huili WU ; Xinle HAN ; Yue TAN ; Minhui LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):252-264
The medicinal use of Malvae Semen has a long history. In this paper, by consulting the ancient materia medica, prescription, agronomy, literature and other aspects of the classics, the name, origin, evolution of scientific name, quality, harvesting and processing, functions and indications and others of Malvae Semen were systematically sorted out and verified, so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shennong Bencaojing began to use Dongkuizi as the correct name, which was used in the past dynasties, and there were also aliases such as Kuicaizi, Huacai, and Kuizi. Through the original research, it can be seen that Kuicai is the mainstream original plant of Malvae Semen, that is, Malva verticillata var. crispa, the Alcea rosea and M. cathayensis are also used. In modern times, the seeds of Abutilon theophrasti have been passed off as Malvae Semen, while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties, the cultivation of Kuicai has been decreasing, while A. theophrasti is more common and easy to obtain, and Abutili Semen and Malvae Semen are similar in morphology and confused, which should be corrected. In addition, Malvae Fructus is a Mongolian customary medicinal herb, which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai, as an important vegetable in history, was widely cultivated and gradually shrunk after the Song dynasty, it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies, full grain, grayish brown color, no mud, and no impurities. The harvesting is generally in the autumn and winter. After drying, it is seeded, sieved peel and impurities, mashed, or slightly stir-fried to yellow-white color with gentle fire. It is sweet, cold and slippery in nature and taste, with the main effects of laxation, diuresis, lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity, promoting diuresis and removing nebula, the efficacy is quite different from that of Malvae Semen. Based on the results of textual research, it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas, the corresponding processing methods should be selected according to the requirements of drug processing in the formulas, while the raw products are recommended to be used if the processing is not specified.
5.Clinical efficacy of escitalopram combined with transcutaneous cervical vagus nerve stimulation therapy for patients with major depressive disorder and its effect on plasma IL-6 and IL-10 levels
Jin LI ; Jinbo SUN ; Di WU ; Wenjun WU ; Runzhu SUN ; Shanshan XUE ; Yapeng CUI ; Huaning WANG ; Yihuan CHEN
Sichuan Mental Health 2025;38(1):7-13
BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression, which may contribute to the anti-inflammatory properties of vagus nerve stimulation (VNS), whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation (tcVNS) in treating major depressive disorder (MDD) and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression, anxiety and sleep quality as well as the plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in MDD patients, in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21, 2019 to April 17, 2024, 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group (n=23) and control group (n=22) using random number table method. All patients were treated with escitalopram. On this basis, study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation, and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment, Hamilton Depression Scale-17 item (HAMD-17) was used to assess depressive symptoms, and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score, anxiety/somatization subfactor score and insomnia subfactor score in both groups (Wald χ2=315.226, 495.481, 82.420, P<0.01). After 4 weeks of treatment, HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group, with statistically significant differences (Wald χ2=4.967, 32.543, P<0.05 or 0.01), while no statistically significant difference was found in the insomnia subfactor score between two groups (Wald χ2=0.819, P=0.366). Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups (Wald χ2=21.792, 5.242, P<0.05 or 0.01). Compared with baseline data, a reduction in plasma IL-6 levels was detected in both groups (Wald χ2=22.015, 6.803, P<0.01), and an increase in plasma IL-10 levels was reported in study group (Wald χ2=5.118, P=0.024) after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms, anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally, it helps reduce plasma IL-6 levels and increase IL-10 levels. [Funded by Shaanxi Provincial Key Research and Development Program-General Project (number, 2023-YBSF-185), www.clinicaltrials.gov number, NCT04037111]
6.Herbal Textual Research on Malvae Semen in Famous Classical Formulas
Dongxue CHEN ; Yibo LIU ; Yangyang YU ; Guoshuai LYU ; Huili WU ; Xinle HAN ; Yue TAN ; Minhui LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):252-264
The medicinal use of Malvae Semen has a long history. In this paper, by consulting the ancient materia medica, prescription, agronomy, literature and other aspects of the classics, the name, origin, evolution of scientific name, quality, harvesting and processing, functions and indications and others of Malvae Semen were systematically sorted out and verified, so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shennong Bencaojing began to use Dongkuizi as the correct name, which was used in the past dynasties, and there were also aliases such as Kuicaizi, Huacai, and Kuizi. Through the original research, it can be seen that Kuicai is the mainstream original plant of Malvae Semen, that is, Malva verticillata var. crispa, the Alcea rosea and M. cathayensis are also used. In modern times, the seeds of Abutilon theophrasti have been passed off as Malvae Semen, while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties, the cultivation of Kuicai has been decreasing, while A. theophrasti is more common and easy to obtain, and Abutili Semen and Malvae Semen are similar in morphology and confused, which should be corrected. In addition, Malvae Fructus is a Mongolian customary medicinal herb, which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai, as an important vegetable in history, was widely cultivated and gradually shrunk after the Song dynasty, it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies, full grain, grayish brown color, no mud, and no impurities. The harvesting is generally in the autumn and winter. After drying, it is seeded, sieved peel and impurities, mashed, or slightly stir-fried to yellow-white color with gentle fire. It is sweet, cold and slippery in nature and taste, with the main effects of laxation, diuresis, lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity, promoting diuresis and removing nebula, the efficacy is quite different from that of Malvae Semen. Based on the results of textual research, it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas, the corresponding processing methods should be selected according to the requirements of drug processing in the formulas, while the raw products are recommended to be used if the processing is not specified.
7.Structure, content and data standardization of rehabilitation medical records
Yaru YANG ; Zhuoying QIU ; Di CHEN ; Zhongyan WANG ; Meng ZHANG ; Shiyong WU ; Yaoguang ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Jian YANG ; Na AN ; Yuanjun DONG ; Xiaojia XIN ; Xiangxia REN ; Ye LIU ; Yifan TIAN
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):21-32
ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.
8.Pharmacoeconomic evaluation of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy
Hai LIANG ; Runan XIA ; Panpan DI ; Mengmeng ZHAO ; Pengcheng ZHANG ; Yashen HOU ; Hong ZHANG ; Wei WU ; Miao YANG
China Pharmacy 2025;36(1):86-90
OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy (DN). METHODS From the perspective of healthcare service providers, a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months, a simulation period of 15 years and an annual discount rate of 5%. At the same time, one-way sensitivity analysis and probability sensitivity analysis were performed, and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan, and the accumulative utility was 8.052 4 quality-adjusted life year (QALYs); the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan, and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value, DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio, but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients, finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.
10.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.

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