1.Mechanism of Liangfang Wenjing Decoction in Regulating Endoplasmic Reticulum Stress to Reduce Apoptosis and Alleviate Ovarian Microvascular Injury in Rats with Cold Coagulation and Blood Stasis Syndrome
Tianyuan LYU ; Xueyan MA ; Yue HU ; Liqun FENG ; Xiaodan SONG ; Lianmin MEI ; Xiumei CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):103-114
ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group, a model group, low-dose (8.1 g·kg-1) and high-dose groups (16.2 g·kg-1) of Liangfang Wenjing decoction, and a 4-phenylbutyric acid (0.1 g·kg-1) group, with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling, Liangfang Wenjing decoction was administered continuously for 21 days, once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay (ELISA) was used to detect serum reproductive hormone levels and levels of endothelin-1 (ET-1), nitric oxide (NO), thrombomodulin (TM), and von Willebrand factor (vWF) in ovarian tissue. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin (HE) staining was performed to observe the ovarian histopathology, flow cytometry to detect ovarian apoptosis rate, and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), Caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol-requiring enzyme1α (IRE1α), p-IRE1α, apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, c-Jun N-terminal kinase (JNK), and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group, the model group showed signs of cold coagulation and blood stasis syndrome, prolonged estrus cycles, and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased (P<0.01). PT, APTT, and TT were reduced (P<0.05, P<0.01), while FIB levels were increased (P<0.05). In ovarian tissue, NO content was decreased, while ET-1, vWF, and TM levels were increased significantly (P<0.01). The apoptosis rate of ovarian cells was markedly increased (P<0.01). Furthermore, p-eNOS/eNOS and Bcl-2 were decreased (P<0.05), whereas Bax, cleaved-Caspase-3/Caspase-3, GRP78, CHOP, p-IRE1α/IRE1α, p-ASK1/ASK1, and p-JNK/JNK expression showed significant increases (P<0.05, P<0.01). Compared with the model group, Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis, gradually restored the estrus cycle, and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated (P<0.05). NO content in ovarian tissue was elevated, while ET-1, vWF, and TM levels were significantly decreased (P<0.05, P<0.01). The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated (P<0.05), while the expression of Bax, cleaved-Caspase-3/Caspase-3, GRP78, CHOP, p-IRE1α/IRE1α, p-ASK1/ASK1, and p-JNK/JNK was significantly decreased (P<0.05, P<0.01). ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress, attenuate apoptosis, and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.
2.Association between dietary diversity and cognitive function among the elderly based on group-based trajectory model
DONG Chunling ; WANG Chong ; GUAN Tianyuan ; LIU Yue ; LI Xueying ; ZHANG Yuhai
Journal of Preventive Medicine 2025;37(9):865-869
Objective:
To analyze the association between dietary diversity and cognitive function among the elderly using group-based trajectory model, so as to provide the basis for formulating dietary intervention strategies to prevent cognitive impairment.
Methods:
Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) project, demographic information, lifestyle behaviors, psychological well-being, and activities of daily living of elderly individuals aged ≥65 years from 2008 to 2018 were collected. Dietary diversity was assessed using a food frequency questionnaire, with a score of <7 points defined as low dietary diversity. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). A group-based trajectory model was established based on cognitive function scores from 2008 to 2018 to analyze the trajectories of cognitive function change. The association between dietary diversity and cognitive function was analyzed using a multinomial logistic regression model.
Results:
A total of 1 613 individuals were collected, with a median age was 72.00 (interquartile range, 10.00) years. There were 810 males (50.22%) and 803 females (49.78%). The group-based trajectory model analysis categorized the participants into three groups: the low-level normal group, the high-level normal group, and the slow-then-rapid decline group, comprising 796 (49.35%), 585 (36.27%), and 232 (14.38%) individuals, respectively. Among these groups, the numbers of individuals with low dietary diversity were 497 (62.44%), 311 (53.16%), and 166 (71.55%), respectively, with a statistically significant difference (P<0.05). Multinomial logistic regression analysis showed that after adjusting for demographic information, lifestyle behaviors, psychological well-being, and activities of daily living, compared with the high-level normal group, low dietary diversity was statistically associated with cognitive function in the slow-then-rapid decline group (OR=1.622, 95%CI: 1.103-2.384).
Conclusion
Low dietary diversity may increase the risk of cognitive impairment among the elderly.
3.Expression of STEAP1 in Pulmonary Hypertension and Potential Clinical Value
Xin WANG ; Tianyuan YUE ; Chen LI
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(5):609-616
Objective To investigate the expression pattern of six-transmembrane epithelial antigen of prostate 1(STEAP1)in pulmonary hypertension(PH)rat model and explore its potential clinical value.Methods A hypoxia-induced pulmonary arte-rial smooth muscle cell(PASMC)model was established,and the expression levels of STEAP1 in the hypoxia cell model were detected using Western blot and immunofluorescence analysis.Nine patients diagnosed with PH through right heart catheteriza-tion during hospitalization in the Division of Cardiovascular Surgery at Tongji Hospital,Tongji Medical College,Huazhong Uni-versity of Science and Technology,were selected as the PH group.Four organ donors without pulmonary disease were selected as the control group.Western blot analysis was used to detect STEAP1 expression levels in lung tissue from both groups.A rat PH model was established by Sugen5416 couple with chronic hypoxia treatment(SuHx,and control rats were housed in an at-mospheric environment).Hematoxylin-eosin staining and immunohistochemistry staining were used to detect α-SMA expression in lung tissue,and the degree of pulmonary artery perivascular cluster lesions and vascular muscularization in model rats was as-sessed.Dual-color immunofluorescence staining was used to co-stain α-SMA and STEAP1 to detect the expression levels and tis-sue localization of STEAP1 in the lung tissue of model rats.Bioinformatics methods were employed to analyze the potential downstream regulatory mechanisms of STEAP1.Results STEAP1 expression level was significantly upregulated in the hypoxi-a-induced PASMCs.STEAP1 expression level was also upregulated in the lung tissue of PH patients.Compared with the control group,the pulmonary arteries of rats with PH showed significant remodeling,particularly with marked thickening of the pulmo-nary arterial smooth muscle layer;STEAP1 expression was significantly upregulated in the thickened pulmonary arterial smooth muscle layer of rats with PH(P<0.01).Bioinformatic analysis suggested that the downstream regulatory mechanisms of STEAP1 were enriched in signaling pathways such as apoptosis.Conclusion STEAP1 expression level is upregulated in the thickened pulmonary arterial smooth muscle layer in PH,suggesting that it may be associated with the pathological mechanisms of pulmonary vascular remodeling and may participate in the development of PH through signaling pathways such as apopto-sis.Further exploration of STEAP1 may uncover new targets for basic research and clinical prevention and treatment.
4.Expression of STEAP1 in Pulmonary Hypertension and Potential Clinical Value
Xin WANG ; Tianyuan YUE ; Chen LI
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(5):609-616
Objective To investigate the expression pattern of six-transmembrane epithelial antigen of prostate 1(STEAP1)in pulmonary hypertension(PH)rat model and explore its potential clinical value.Methods A hypoxia-induced pulmonary arte-rial smooth muscle cell(PASMC)model was established,and the expression levels of STEAP1 in the hypoxia cell model were detected using Western blot and immunofluorescence analysis.Nine patients diagnosed with PH through right heart catheteriza-tion during hospitalization in the Division of Cardiovascular Surgery at Tongji Hospital,Tongji Medical College,Huazhong Uni-versity of Science and Technology,were selected as the PH group.Four organ donors without pulmonary disease were selected as the control group.Western blot analysis was used to detect STEAP1 expression levels in lung tissue from both groups.A rat PH model was established by Sugen5416 couple with chronic hypoxia treatment(SuHx,and control rats were housed in an at-mospheric environment).Hematoxylin-eosin staining and immunohistochemistry staining were used to detect α-SMA expression in lung tissue,and the degree of pulmonary artery perivascular cluster lesions and vascular muscularization in model rats was as-sessed.Dual-color immunofluorescence staining was used to co-stain α-SMA and STEAP1 to detect the expression levels and tis-sue localization of STEAP1 in the lung tissue of model rats.Bioinformatics methods were employed to analyze the potential downstream regulatory mechanisms of STEAP1.Results STEAP1 expression level was significantly upregulated in the hypoxi-a-induced PASMCs.STEAP1 expression level was also upregulated in the lung tissue of PH patients.Compared with the control group,the pulmonary arteries of rats with PH showed significant remodeling,particularly with marked thickening of the pulmo-nary arterial smooth muscle layer;STEAP1 expression was significantly upregulated in the thickened pulmonary arterial smooth muscle layer of rats with PH(P<0.01).Bioinformatic analysis suggested that the downstream regulatory mechanisms of STEAP1 were enriched in signaling pathways such as apoptosis.Conclusion STEAP1 expression level is upregulated in the thickened pulmonary arterial smooth muscle layer in PH,suggesting that it may be associated with the pathological mechanisms of pulmonary vascular remodeling and may participate in the development of PH through signaling pathways such as apopto-sis.Further exploration of STEAP1 may uncover new targets for basic research and clinical prevention and treatment.
5.Analysis of dosimetric characteristics of proton radiotherapy in 3 cases of abdominal and pelvic tumors
Jinghao DUAN ; Jinbo YUE ; Cheng TAO ; Shizhang WU ; Chengqiang LI ; Tianyuan DAI ; Jinhu CHEN ; Tong BAI ; Jian ZHU
Journal of International Oncology 2025;52(7):455-461
Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) for typical abdominal and pelvic tumors.Methods:Three patients with abdominal and pelvic tumors (one case each of liver cancer, cervical cancer, and prostate cancer) admitted to Shandong Cancer Hospital and Institute from January to June 2024 were selected as the research subjects. IMPT and IMRT plans were designed for each case based on clinical target volume (CTV) and organs at risk (OARs) constraints. Dosimetric parameters, including conformity index (CI), homogeneity index (HI), and gradient index (GI) for target coverage, as well as OARs dose metrics, were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all three cases, IMRT plan demonstrated higher CI values (0.82, 0.81, and 0.86) compared to IMPT plan (0.61, 0.62, and 0.43). IMPT plan yielded lower HI values (0.053, 0.075, and 0.020) than IMRT plan (0.060, 0.120, and 0.080) and lower GI values (3.45, 2.63, and 3.80 vs. 7.28, 4.76, and 4.66 for IMRT plan). In liver cancer, IMPT plan reduced the D mean of normal liver tissues and right kidney by 37.8% and 78.5%, respectively, and decreased the D max of spinal cord by 13.2%. For cervical cancer, IMPT plan reduced the V 30 of the small bowel by 22.0%, D mean of the bladder, rectum and bone marrow by 15.7%, 14.3% and 12.6%, and spinal cord D max by 4.8%. In prostate cancer, IMPT plan lowered bladder and rectal D mean by 14.9% and 36.5%, respectively, but resulted in an increase of 35.3% and 6.1% in the D mean and V 40 of the left femoral head, respectively, and an increase of 23.6% and 10.8% in the D mean and V 40 of the right femoral head, respectively. IMPT plan reduced the volumes receiving 10%, 30%, and 50% of the prescription dose by 48.9%-64.8%, 22.0%-47.0%, and 22.0%-57.7%, respectively, compared to IMRT plan. Conclusions:Comparison between IMPT and IMRT plans for abdominopelvic tumors: IMPT plan offers advantages in reducing doses to normal organs such as the liver, kidneys, spinal cord, small intestine, rectum, and bladder. However, its advantage is less pronounced regarding the dose to the femoral heads. IMPT plan notably minimizes additional dose deposition within the body.


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