1.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
2.Disease burden of chronic kidney disease attributable to high BMI in China and trend prediction in 1992-2021
Hong LIU ; Guimao YANG ; Yan SUI ; Xia ZHANG ; Xuebing CHENG ; Yaxing WU ; Xu GUO ; Yanfeng REN
Journal of Public Health and Preventive Medicine 2025;36(1):27-31
Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.
3.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.
4.Effect of exercise on cancer patients with anxiety and depression during chemotherapy: a meta-analysis
Yicheng YANG ; Dandan WANG ; Qunce SHEN ; Lei ZHANG ; Xueping WU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):184-193
ObjectiveTo explore the effect of exercise on anxiety and depression in cancer patients during chemotherapy, as well as the optimal exercise dosage. MethodsA PICO framework was constructed, and randomized controlled trials (RCTs) on the effect of exercise on anxiety and depression in cancer patients during chemotherapy were retrieved from databases of PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang data, from the establishment to November, 2023. The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database (PEDro) scale. Data were synthesized and analyzed using RevMan 5.3, and the risk of bias was evaluated using Stata 18.0. ResultsA total of 13 RCTs involving 1 340 subjects were included. The scores of PEDro scale were five to eight. Exercise interventions significantly improved anxiety (SMD = -0.70, 95%CI -1.18 to -0.22, P = 0.004) and depression (SMD = -0.89, 95%CI -1.43 to -0.34, P = 0.002) compared to the control group. Subgroup analyses showed that, the exercise effect on anxiety was less than 45 minutes a time (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), more than three times a week (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), and less than twelve weeks (SMD = -0.21, 95%CI -0.36 to -0.07, P = 0.005). For depression, it was less than 45 minutes a time (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), more than three times a week (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), and less than twelve weeks (SMD = -0.52, 95%CI -0.92 to -0.13, P = 0.01). Moderate to high-intensity exercise interventions significantly outperformed the control group in improving anxiety (SMD = -0.21, 95%CI -0.37 to -0.06, P = 0.007) and depression (SMD = -0.21, 95%CI -0.41 to -0.01, P = 0.04). ConclusionExercise interventions can effectively improve anxiety and depression in cancer patients during chemotherapy, and it suggests for high-intensity exercise, less than 45 minutes a time, more than three times a week, and less than twelve weeks.
5.Protective effect of Shenfu injection against neonatal hypoxic-ischemic brain injury by inhibiting the ferroptosis
Xiaotong Zhang ; Meng Zhang ; Gang Li ; Yang Hu ; Yajing Xun ; Hui Ding ; Donglin Shen ; Ming Wu
Acta Universitatis Medicinalis Anhui 2025;60(1):31-40
Objective :
To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis.
Methods :
An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression.
Results :
Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01).
Conclusion
Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.
6.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
7.Cost-effectiveness analysis of gonadotropin-releasing hormone analogue combined with recombinant human growth hormone in the treatment of central precocious puberty
Chunsong YANG ; Jianing LIU ; Zheng LIU ; Linan ZENG ; Jin WU ; Lingli ZHANG
China Pharmacy 2025;36(1):79-85
OBJECTIVE To compare the long-term cost-effectiveness of gonadotrophin-releasing hormone analogue (GnRHa) combined with recombinant human growth hormone (rhGH) (combination therapy regimen) versus GnRHa monotherapy (monotherapy regimen) in the treatment of central precocious puberty (CPP). METHODS From the societal perspective and based on a real-world study conducted at West China Second Hospital of Sichuan University, the cost-effectiveness analysis was performed to compare the long-term cost-effectiveness of two pharmacotherapy regimens for CPP girls, with final height as outcome indexes, using per capita disposable income of rural residents and urban residents (20 133-49 283 yuan) in 2022 as the social willing-to-pay (WTP) threshold. The robustness of the basic analysis result was verified by using one-way sensitivity analysis and probability sensitivity analysis, and the cost-effectiveness of different combinations of long-acting preparations was compared using scenario analysis. RESULTS The basic analysis result showed that the combination therapy regimen required an additional cost of 25 193.49 yuan for every one-centimeter improvement in the final height of girls with CPP compared with the monotherapy regimen, which was not cost-effective for residents in rural areas, but it was cost-effective for residents in urban areas. One-way sensitivity analysis showed that the uncertain factors with potential impacts on the results were, in order, the price of rhGH, the final height of pediatric patients in the combination therapy regimen group, the course of rhGH in the combination therapy regimen group, and the final height of pediatric patients in the monotherapy regimen group. Probabilistic sensitivity analysis indicated that the probability of the combination therapy regimen being cost-effective was higher than that of the monotherapy regimen when WTP was more than 26 010 yuan/cm. When GnRHa long-acting preparation was used for intramuscular injection every 3 months, the combination therapy regimen was not cost-effective for rural residents, but was cost-effective for urban residents; when rhGH long-acting preparation was injected subcutaneously once a week, the combination therapy regimen was not cost-effective for residents in both rural areas and urban areas. CONCLUSIONS The combination of GnRHa and rhGH is only recommended for CPP children with better affordability to improve final height. The benefits, risks, and affordability of treatment should be comprehensively considered before the decisions on pharmacotherapy, to avoid abuse of rhGH due to the blind pursuit of height growth.
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.
9.Mechanism of Modified Shaofu Zhuyutang in Antagonising Ectopic Endometrial Tissue Fibrosis Based on Cellular Pyroptosis Mediated by TRL4/NF-κB/NLPR3 Signaling Pathway
Zuoliang ZHANG ; Jiaxing WANG ; Wanrun WANG ; Xiangyu LIN ; Bin YUE ; Zhirui ZHANG ; Yinan WANG ; Yaling YANG ; Dongqing WEI ; Cancan HUANG ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):19-28
ObjectiveTo investigate the mechanism of action of modified Shaofu Zhuyutang in antagonizing cellular pyroptosis and fibrosis in ectopic endometrial tissues of endometriosis through the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3 (TRL4/NF-κB/NLPR3) signaling pathway. MethodsSeventy-two SPF-grade female SD rats were randomly divided into a sham-operated group (n = 12) and a modeling group (n = 60). The rats in the sham-operated group underwent a caesarean section, while the rats in the modeling group were used to establish an endometriosis model through the auto-transplantation method. After successful modeling, the animals were randomly divided into the model group, progesterone group (0.25 mg·kg-1), and modified Shaofu Zhuyutang low-, medium-, and high-dose groups (7.5, 15, 30 g·kg-1), with 12 animals in each group. After 4 weeks of drug administration, voluntary activity and heat pain latency were observed. The rats were sacrificed for tissue collection, and Masson staining were used to observe histopathological changes in the endometrial tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). Immunohistochemistry (IHC) was used to detect the protein expression area of tumor necrosis factor-related factor 6 (TRAF6) and NLPR3 in the endometrial tissues. Immunofluorescence (IF) was used to detect the relative fluorescence intensity of Caspase-1 and gasdermin D (GSDMD) in the endometrial tissues. Western blot was employed to measure the relative expression of TRL4, myeloid differentiation factor 88 (MyD88), TRAF6, NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), and NLPR3 proteins in endometrial tissues. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of TRL4, MyD88, TRAF6, NF-κB, and NLPR3 in the endometrial tissues. ResultsCompared with the sham-operated group, rats in the model group showed reduced voluntary activity and shorter heat pain latency. Serum levels of IL-18, IL-1β, TNF-α, and TGF-β were elevated. The relative expression areas of TRAF6 and NLPR3 proteins were increased, and the relative fluorescence intensity of Caspase-1 and GSDMD was enhanced. The relative expression of TRL4, MyD88, TRAF6, NF-κB p65, p-NF-κB p65, and NLPR3 proteins, along with the expression of TRL4, MyD88, TRAF6, NF-κB, and NLPR3 mRNA, were significantly increased (P<0.01). Compared with the model group, rats in the progesterone group and the modified Shaofu Zhuyutang medium- and high-dose groups exhibited improved voluntary activity, longer heat pain latency, the fibrosis of endometrial tissue is alleviated. Serum levels of IL-18, IL-1β, TNF-α, and TGF-β were decreased. The relative expression areas of TRAF6 and NLPR3 proteins decreased, and the relative fluorescence intensity of Caspase-1 and GSDMD weakened. The relative expression of TRL4, MyD88, TRAF6, p-NF-κB p65, NLPR3 proteins, and TRL4, MyD88, TRAF6, NF-κB, and NLPR3 mRNA expression were reduced (P<0.05, P<0.01). ConclusionModified Shaofu Zhuyutang may play a therapeutic role in endometriosis by interfering with key proteins in the TRL4/NF-κB/NLPR3 signaling pathway, reducing NLRP3 inflammasome-induced cellular pyroptosis, antagonizing the fibrosis process in ectopic endometrial tissues, improving the inflammatory microenvironment in the pelvic cavity, and alleviating pain.
10.Mechanism of Modified Shaofu Zhuyutang in Treatment of Endometriosis Based on EGFR/PI3K/Akt Signaling Pathway
Yaling YANG ; Wanrun WANG ; Zuoliang ZHANG ; Xiangyu LIN ; Jiaxing WANG ; Cancan HUANG ; Xiujia JI ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):29-38
ObjectiveTo observe the effects of modified Shaofu Zhuyutang on key proteins of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in SD rats with endometriosis. MethodsAfter successful establishment of an endometriosis model in 60 female SD rats of SPF grade via the auto-transplantation method, the rats were randomly divided into a model group, modified Shaofu Zhuyutang high-, medium-, and low-dose groups, and a gestrinone group, with another 12 rats serving as a blank group. The blank and model groups were administered 10 mL·kg-1 normal saline, while the high-, medium-, and low-dose groups received 30, 15, and 7.5 g·kg-1 modified Shaofu Zhuyutang, respectively. The gestrinone group was administered 0.25 mg·kg-1 gestrinone suspension. After four weeks of treatment, uterine contractions were induced with 2 U of oxytocin, and the writhing response of rats was observed. After 24 h, the rats were euthanized, and the weight and volume of ectopic endometrial tissue were recorded. Hematoxylin-eosin (HE) staining was used to observe pathological changes in endometrial tissues, while the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was used to evaluate the apoptosis rate of endometrial tissues. Immunofluorescence was used to detect the relative expression areas of the B-cell lymphoma-2 gene-associated promoter (Bad) and B-cell lymphoma-2 (Bcl-2) proteins in endometrial tissues. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), and EGFR were measured by enzyme-linked immunosorbent assay (ELISA). The relative protein expression levels of EGFR, PI3K, phosphorylated PI3K (p-PI3K), Akt, and phosphorylated Akt (p-Akt) in endometrial tissues were analyzed by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of EGFR, PI3K, and Akt. ResultsCompared with the blank group, the model group showed endometrial thickening, glandular and mesenchymal hyperplasia, a significant decrease in the relative expression area of Bad in ectopic endometrial tissues, a significant increase in the relative expression area of Bcl-2, and a significant reduction in the apoptosis rate as indicated by TUNEL staining. Serum levels of IL-1β, IL-6, TNF-α, EGF, and EGFR were significantly elevated (P<0.01). The relative protein expression levels of EGFR, PI3K, p-PI3K, Akt, and p-Akt, as well as the mRNA expression levels of EGFR, PI3K, and Akt, were also significantly increased (P<0.01). Compared with the model group, the high- and medium-dose groups of modified Shaofu Zhuyutang and the gestrinone group exhibited reduced glandular and mesenchymal hyperplasia to varying degrees, with dilated glandular lumens. The number of writhing responses was significantly reduced, the latency to writhing response was significantly prolonged, and the weight and volume of ectopic endometrial tissue were significantly decreased. The relative expression area of Bad in ectopic endometrial tissue was significantly increased, the relative expression area of Bcl-2 was significantly decreased, and the apoptosis rate was significantly elevated as shown by TUNEL staining. Serum levels of IL-1β, IL-6, TNF-α, EGF, and EGFR were significantly reduced, and the relative protein expression levels of EGFR, PI3K, p-PI3K, Akt, and p-Akt, as well as the mRNA expression levels of EGFR, PI3K, and Akt, were significantly decreased (P<0.05,P<0.01). ConclusionModified Shaofu Zhuyutang may exert therapeutic effects on endometriosis by interfering with key proteins of the EGFR/PI3K/Akt signaling pathway and inducing apoptosis in ectopic endometrial tissue.


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