OBJECTIVE To explore the clinical efficacy of the Yushen Yangluan Formula in treating diminished ovarian reserve(DOR)with kidney essence deficiency based on mitochondrial energy metabolism and oxidative stress.METHODS A total of 70 pa-tients diagnosed with DOR due to kidney essence deficiency,who visited the gynecology department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from September 2023 to June 2024,were selected.The patients were randomly divided into two groups according to the random number table method.The treatment group(35 cases)received the Yushen Yangluan Formula,while the control group(35 cases)received a Chinese herbal placebo,with treatment lasting for 3 months,and during the treatment pe-riod,one case dropped out from each group.Antral follicle count(AFC),traditional Chinese medicine(TCM)syndrome scores,and serum levels of anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),re-active oxygen species(ROS),and adenosine triphosphate(ATP)levels were compared between the two groups.RESULTS After treatment,the TCM syndrome scores for kidney deficiency in both groups decreased compared to before treatment(P<0.05,P<0.01),with the experimental group showing greater improvement than the control group(P<0.01).Following treatment,the FSH levels in the experimental group decreased compared to before treatment(P<0.05),while AMH levels increased(P<0.05),and the antral follicle count(AFC)also increased significantly(P<0.01),with the experimental group outperforming the control group(P<0.05,P<0.01).After treatment,serum ROS levels in the experimental group decreased(P<0.01),and ATP levels increased(P<0.01),with the experimental group showing superior results compared to the control group(P<0.01).CONCLUSION Yushen Yangluan Formu-la can improve the ovarian function and TCM syndrome score of patients with DOR of kidney essence deficiency type,which may be re-lated to improving mitochondrial energy metabolism and reducing oxidative stress.

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

OBJECTIVE To explore the clinical efficacy of the Yushen Yangluan Formula in treating diminished ovarian reserve(DOR)with kidney essence deficiency based on mitochondrial energy metabolism and oxidative stress.METHODS A total of 70 pa-tients diagnosed with DOR due to kidney essence deficiency,who visited the gynecology department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from September 2023 to June 2024,were selected.The patients were randomly divided into two groups according to the random number table method.The treatment group(35 cases)received the Yushen Yangluan Formula,while the control group(35 cases)received a Chinese herbal placebo,with treatment lasting for 3 months,and during the treatment pe-riod,one case dropped out from each group.Antral follicle count(AFC),traditional Chinese medicine(TCM)syndrome scores,and serum levels of anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),re-active oxygen species(ROS),and adenosine triphosphate(ATP)levels were compared between the two groups.RESULTS After treatment,the TCM syndrome scores for kidney deficiency in both groups decreased compared to before treatment(P<0.05,P<0.01),with the experimental group showing greater improvement than the control group(P<0.01).Following treatment,the FSH levels in the experimental group decreased compared to before treatment(P<0.05),while AMH levels increased(P<0.05),and the antral follicle count(AFC)also increased significantly(P<0.01),with the experimental group outperforming the control group(P<0.05,P<0.01).After treatment,serum ROS levels in the experimental group decreased(P<0.01),and ATP levels increased(P<0.01),with the experimental group showing superior results compared to the control group(P<0.01).CONCLUSION Yushen Yangluan Formu-la can improve the ovarian function and TCM syndrome score of patients with DOR of kidney essence deficiency type,which may be re-lated to improving mitochondrial energy metabolism and reducing oxidative stress.

Objective:To observe the effect of the Yushen Yangluan decoction on ovarian reserve function in mice with diminished ovarian reserve (DOR) and to explore its mechanism of action based on the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor A (VEGFA) signaling pathway.Methods:Mechanism analysis was conducted using artificial intelligence-based network pharmacology. Fifty 6-week-old female C57BL/6 mice were randomly divided into five groups according to body weight, with 10 mice in each group. The groups were as follows: control group, model group, low-dose Traditional Chinese Medicine (TCM) group, medium-dose TCM group, and high-dose TCM group. Hematoxylin-eosin staining was used to observe the number of antral follicles in the ovaries, enzyme-linked immunosorbent assay was employed to detect serum hormone levels, and TdT-mediated dUTP nick end labeling (TUNEL) was used to assess apoptosis in ovarian granulosa cells. Immunohistochemistry (IHC) was performed to detect ovarian expression of HIF-1α, and Western blotting was used to measure the protein expressional levels of HIF-1α, VEGFA, and B-cell lymphoma-2 (BCL2) in the ovaries.Results:After treating DOR model mice with the Yushen Yangluan decoction at low, medium, and high dosages, the ovarian antral follicle count of the mice in the TCM groups was all higher than that in the model group ( P=0.024, P<0.001, P<0.001), the follicle-simulating hormone level was lower than that in the model group ( P=0.003, P<0.001, P<0.001), and the serum anti-Müllerian hormone level in the medium-and high-dose TCM groups was higher than that in the model group ( P=0.001, P<0.001). Network pharmacology and molecular docking suggested that the formula may influence the HIF signaling pathway through core targets such as HIF-1α, BCL2 and VEGFA. TUNEL assays indicated that the apoptosis rate of ovarian granulosa cells in the low-, medium-, and high-dose TCM groups was significantly lower than that in the model group ( P=0.017, P=0.003, P<0.001). Immunohistochemistry results showed that the expression level of HIF-1α in the granulosa cells of the follicles in the low-, medium- and high-dose TCM groups was significantly higher than that in the model group ( P=0.008, P<0.001, P<0.001). Western blotting analysis indicated that the protein expression level of HIF-1α in medium-, and high-dose TCM groups was significantly higher than that in the model group ( P=0.004, P<0.001), and the protein expression levels of VEGFA and BCL2 in low-, medium-, and high-dose TCM groups were significantly higher than those in the model group ( P=0.003, P=0.002, P=0.001; P=0.029, P=0.007, P=0.001). Conclusion:The Yushen Yangluan decoction may exert its therapeutic effect by inhibiting apoptosis of ovarian granulosa cells through the HIF-1α/VEGFA signaling pathway.

Objective:To observe the effect of the Yushen Yangluan decoction on ovarian reserve function in mice with diminished ovarian reserve (DOR) and to explore its mechanism of action based on the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor A (VEGFA) signaling pathway.Methods:Mechanism analysis was conducted using artificial intelligence-based network pharmacology. Fifty 6-week-old female C57BL/6 mice were randomly divided into five groups according to body weight, with 10 mice in each group. The groups were as follows: control group, model group, low-dose Traditional Chinese Medicine (TCM) group, medium-dose TCM group, and high-dose TCM group. Hematoxylin-eosin staining was used to observe the number of antral follicles in the ovaries, enzyme-linked immunosorbent assay was employed to detect serum hormone levels, and TdT-mediated dUTP nick end labeling (TUNEL) was used to assess apoptosis in ovarian granulosa cells. Immunohistochemistry (IHC) was performed to detect ovarian expression of HIF-1α, and Western blotting was used to measure the protein expressional levels of HIF-1α, VEGFA, and B-cell lymphoma-2 (BCL2) in the ovaries.Results:After treating DOR model mice with the Yushen Yangluan decoction at low, medium, and high dosages, the ovarian antral follicle count of the mice in the TCM groups was all higher than that in the model group ( P=0.024, P<0.001, P<0.001), the follicle-simulating hormone level was lower than that in the model group ( P=0.003, P<0.001, P<0.001), and the serum anti-Müllerian hormone level in the medium-and high-dose TCM groups was higher than that in the model group ( P=0.001, P<0.001). Network pharmacology and molecular docking suggested that the formula may influence the HIF signaling pathway through core targets such as HIF-1α, BCL2 and VEGFA. TUNEL assays indicated that the apoptosis rate of ovarian granulosa cells in the low-, medium-, and high-dose TCM groups was significantly lower than that in the model group ( P=0.017, P=0.003, P<0.001). Immunohistochemistry results showed that the expression level of HIF-1α in the granulosa cells of the follicles in the low-, medium- and high-dose TCM groups was significantly higher than that in the model group ( P=0.008, P<0.001, P<0.001). Western blotting analysis indicated that the protein expression level of HIF-1α in medium-, and high-dose TCM groups was significantly higher than that in the model group ( P=0.004, P<0.001), and the protein expression levels of VEGFA and BCL2 in low-, medium-, and high-dose TCM groups were significantly higher than those in the model group ( P=0.003, P=0.002, P=0.001; P=0.029, P=0.007, P=0.001). Conclusion:The Yushen Yangluan decoction may exert its therapeutic effect by inhibiting apoptosis of ovarian granulosa cells through the HIF-1α/VEGFA signaling pathway.

Objective:To explore the medication law and academic thought of Professor Hu Guohua in treating diminished ovarian reserve (DOR) based on data mining.Methods:Collecting the medical records of DOR patients treated by Prof. Hu from January 1, 2021 to March 31, 2022. The TCM symptoms, tongue and pulse conditions, as well as the frequency, taste, meridian tropism and efficacy categories of TCM were analyzed by using the Traditional Chinese Medicine Inheritance Computing Platform V3.0 software. Commonly used drug combination analysis, high-frequency drug network relationship analysis, association rule analysis based on Apriori algorithm, cluster analysis based on K-means clustering algorithm, and core prescriptions were summarized.Results:A total of 85 DOR patients were included, involving 76 TCM symptoms, 15 tongue images, 11 pulse images. A total of 415 prescriptions were included, involving 164 kinds of Chinese materia medica. High-frequency drugs included Ligustri Lucidi Fructus, Angelicae Sinensis Radix, Astragali Radix, Cuscutae Semen, Herba Leonuri and Rhizoma Atractylodis Macrocephalae. The medicines were mostly warm, mild and cold in property, and the tastes were mostly sweet, bitter and pungent, mainly belonging to the liver, spleen and kidney meridians. 42 high-frequency drug combinations and 6 core prescriptions were obtained.Conclusions:Professor Hu treats DOR with the principle of tonifying the kidney and spleen to regulate body constitution, conditioning Chong Vessel and Conception Vessel to regulate the menstruation, soothing the liver and tranquillizing the heart to regulate the spirit. Professor Hu selects the medicines which are simplified and condensed, and is good at using drugs. The prescriptions are persistent and flexible, concerning the balance.