1.Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Chronic Kidney Disease
Hairui HAN ; Zushun ZHUO ; Long LIN ; Xiangying LIN ; Wenjuan FENG ; Mingshan LIN ; Ziyao CAI ; Zhaoyang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):216-223
ObjectiveTo systematically collate the randomized controlled trials (RCTs) on the intervention of traditional Chinese medicine (TCM) in chronic kidney disease (CKD) and analyze the characteristics of clinical trials and the current situation of outcome indicators, thus providing references for constructing a core outcome set (COS) for CKD. MethodsThe RCTs on the intervention of TCM in CKD were retrieved from CNKI, Wanfang Data, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science with the time interval from January 2022 to December 2024. The risk of bias was evaluated, and the outcome indicators were qualitatively analyzed. ResultsA total of 242 RCTs were included, which reported 238 outcome indicators, with the cumulative frequency of 2 724 times. These outcome indicators can be classified into seven domains: TCM syndromes and diseases (270 times, accounting for 9.90%), symptoms and signs (218 times, 8.00%), physical and chemical examinations (1 609 times, 59.07%), quality of life (29 times, 1.06%), long-term prognosis (6 times, 0.22%), economic evaluation (0 times), and safety events (535 times, 19.64%). The results demonstrated that the RCTs of TCM intervention for CKD had several shortcomings such as the lack of a basis for sample size estimation, lack of standardization in TCM syndrome differentiation and classification, room for improvement in methodological quality, flaws in the design of the timing of efficacy measurement, absence of long-term prognosis evaluation, imbalance in the selection of surrogate and endpoint indicators, disconnection between overall evaluation and individualized assessment, lack of TCM characteristic indicators, and insufficient reporting of safety indicators. ConclusionAt present, the design of outcome indicators in the RCTs for TCM intervention in CKD is still not standardized. It is recommended that future research endeavors to enhance methodological quality, establish a standardized COS for TCM intervention in CKD, and thereby propel the high-quality development of TCM.
2.Determination of Traditional Chinese Medicine Syndrome of Rat Model of Follicular Dysplasia Induced by Tripterygium Glycosides Based on Prescriptions via AMPK/mTOR/HIF-1/VEGF Pathway
Yingying HU ; Xuejuan LIN ; Zushun ZHUO ; Shanshan DING ; Mengting ZHANG ; Guorong LIN ; Long ZHU ; Yuyu XIE ; Yan XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):46-54
ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1 (HIF-1)/vascular endothelial growth factor (VEGF) pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group (n=8) and a modeling group (n=40). The rats in the modeling group were administrated with Tripterygium glycoside suspension (75 mL·kg-1) by gavage for 30 days. The modeled rats were assigned into model, Siwutang (3.69 g·kg-1), Youguiyin (3.11 g·kg-1), Zuoguiyin (7.29 g·kg-1), and Guishenwan (10.35 g·kg-1) groups, with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining, and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay (ELISA) was used to measure the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels, respectively, of AMPK, mTOR, HIF-1, and VEGF in the ovarian tissue. ResultCompared with the normal group, the model group had a disordered estrous cycle, reduced secondary and mature follicles, increased atretic follicles, elevated FSH and LH levels, lowered E2 level, up-regulated mRNA and protein levels of AMPK, and down-regulated mRNA and protein levels of mTOR, HIF-1, and VEGF (P<0.01). Compared with the model group, Guishenwan increased secondary and mature follicles, decreased atretic follicles, lowered the FSH and LH levels, elevated the E2 level, down-regulated the mRNA and protein levels of AMPK, and up-regulated the mRNA and protein levels of mTOR, HIF-1, and VEGF (P<0.01). Compared with Guishenwan group, Siwutang, Youguiyin, and Zuoguiyin decreased mature follicles, increased atretic follicles (P<0.01), elevated the LH (P<0.01) and FSH (P<0.05) levels, and lowered the E2 level (P<0.05). In addition, Youguiyin up-regulated the protein level of AMPK (P<0.05) and down-regulated the mRNA levels of mTOR and HIF-1 (P<0.01) as well as the mRNA and protein levels of VEGF (P<0.01). Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF (P<0.05). Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF (P<0.05). ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway, with the therapeutic effect superior to Zuoguiyin, Youguiyin, and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

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