To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

The Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance Systems in Medical Institutions （T/CACM 1563.2-2024） were the first special guideline in China to systematically assist medical institutions in establishing a pharmacovigilance system tailored to the characteristics of traditional Chinese medicine （TCM）. This guideline was jointly developed with 23 authoritative medical and research institutions in China， under the lead of the Institute of Basic Clinical Medicine， China Academy of Chinese Medical Sciences. The purpose of this guideline was to standardize pharmacovigilance work throughout the entire lifecycle of TCM （including research and development， marketing， and application） and to establish a four-dimensional framework of "organizational structure， institutional system， information platform， and vigilance activities". Key components included the establishment of a TCM Safety Committee， the construction of nine core systems， the development of an information platform that complies with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use （ICH） E2B standards， alongside the risk monitoring， identification， assessment， and control during clinical trials and post-marketing phases. Therefore， this guideline filled a significant gap in the systemic standards for TCM safety management within medical institutions. Strictly adhering to domestic and international laws and regulations， the guideline compilation involved multiple rounds of expert interviews， systematic evidence integration， and broad consensus. This guideline was specified to be applicable to medical institutions at all levels， primarily addressing core issues， including the difficulty in adverse reaction identification， low reporting rates， and incomplete risk management chains due to the complex composition and diverse application of TCM. The compilation process was scientific and rigorous， ensuring alignment with current national laws and regulations， and was registered internationally. In the future， implementation will be promoted through standardized training， tiered dissemination， as well as a post-effect evaluation and dynamic revision mechanism starting two years after publication. All these aimed to enhance medical institutions' proactive capabilities in preventing and controlling TCM safety risks， ensure patient medication safety， and promote the high-quality development of TCM.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

The Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance Systems in Medical Institutions （T/CACM 1563.2-2024） were the first special guideline in China to systematically assist medical institutions in establishing a pharmacovigilance system tailored to the characteristics of traditional Chinese medicine （TCM）. This guideline was jointly developed with 23 authoritative medical and research institutions in China， under the lead of the Institute of Basic Clinical Medicine， China Academy of Chinese Medical Sciences. The purpose of this guideline was to standardize pharmacovigilance work throughout the entire lifecycle of TCM （including research and development， marketing， and application） and to establish a four-dimensional framework of "organizational structure， institutional system， information platform， and vigilance activities". Key components included the establishment of a TCM Safety Committee， the construction of nine core systems， the development of an information platform that complies with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use （ICH） E2B standards， alongside the risk monitoring， identification， assessment， and control during clinical trials and post-marketing phases. Therefore， this guideline filled a significant gap in the systemic standards for TCM safety management within medical institutions. Strictly adhering to domestic and international laws and regulations， the guideline compilation involved multiple rounds of expert interviews， systematic evidence integration， and broad consensus. This guideline was specified to be applicable to medical institutions at all levels， primarily addressing core issues， including the difficulty in adverse reaction identification， low reporting rates， and incomplete risk management chains due to the complex composition and diverse application of TCM. The compilation process was scientific and rigorous， ensuring alignment with current national laws and regulations， and was registered internationally. In the future， implementation will be promoted through standardized training， tiered dissemination， as well as a post-effect evaluation and dynamic revision mechanism starting two years after publication. All these aimed to enhance medical institutions' proactive capabilities in preventing and controlling TCM safety risks， ensure patient medication safety， and promote the high-quality development of TCM.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

Objective:To evaluate the expression of tertiary lymphoid structures (TLS) in renal tissues, and the relationship between TLS and clinicopathological changes and prognosis in idiopathic membranous nephropathy (IMN) patients.Methods:It was a single center retrospective study. The patients with IMN diagnosed by renal biopsy at Shengjing Hospital Affiliated to China Medical University from January 2018 to December 2020 were enrolled, and their clinicopathological data were collected. Immunohistochemistry was used to evaluate the expression of TLS in renal tissues. According to whether TLS expression in renal tissues was positive or not, the patients were divided into TLS-positive group and TLS-negative group, and the baseline differences in clinicopathological data between the two groups were compared. The clinical remission included complete remission and partial remission. Logistic regression analysis was used to analyze the correlation between serum phospholipase A2 receptor (PLA2R) antibody titer and positive TLS expression in renal tissues. Kaplan-Meier survival curve and log-rank test were performed to analyze the differences of proteinuria remission rates between TLS-positive and TLS-negative groups. Cox regression analysis was employed to identify the related factors of proteinuria remission. The receiver operating characteristic (ROC) curve was used to evaluate the value of TLS in predicting proteinuria remission.Results:A total of 120 IMN patients were included in this study, with age of 50.00 (40.00, 57.75) years and 78 (65.00%) males. The 24-hour urinary protein was (7.54±4.14) g, 89 (74.17%) patients were positive for serum PLA2R antibody, and the serum PLA2R antibody titer was 90.49 (48.88, 155.33) RU/ml. Immunohistochemical results showed that TLS was mainly distributed in the renal cortex glomeruli or around renal blood vessels in renal tissues. There were 43 patients in the TLS-positive group and 77 patients in the TLS-negative group. The positive rate of serum PLA2R antibody in the TLS-positive group was 83.72% (36/43). Compared with the TLS-negative group, the TLS-positive group had lower serum albumin ( t=-3.474, P<0.001) and estimated glomerular filtration rate ( Z=-2.076, P=0.045), while serum creatinine ( t=2.006, P=0.028), 24-hour urinary protein ( t=4.140, P<0.001), serum PLA2R antibody titer ( Z=4.628, P=0.001), glomerulosclerosis degree ( Z=2.403, P=0.019), and proportions of hypertension ( χ2=6.511, P=0.011), renal interstitial fibrosis ( χ2=4.088, P=0.043), renal interstitial inflammatory cell infiltration ( χ2=9.261, P=0.002), tubular atrophy ( χ2=4.936, P=0.026) and extremely high-risk of kidney disease progression ( χ2=9.352, P=0.002) were higher. Multivariate logistic regression analysis showed that serum PLA2R antibody titer was an independent factor correlated with positive TLS expression in renal tissues ( OR=1.014, 95% CI 1.007-1.021). The median follow-up time was 18.00 (95% CI 16.07-19.93) months. Kaplan-Meier survival curve showed that the proteinuria remission rate in the TLS-positive group was lower than that in the TLS-negative group (Log-rank χ2=9.339, P=0.002). Cox regression analysis showed that positive TLS expression was an independent factor correlated with proteinuria remission ( HR=0.228, 95% CI 0.177-0.297). ROC curve showed that TLS had a certain clinical predictive value for proteinuria remission ( AUC=0.703, 95% CI 0.608-0.798). Conclusions:IMN patients with positive TLS expression in renal tissues have a lower proteinuria remission rate, more severe pathological damage, and a higher risk of disease progression. TLS is expected to become a pathological marker for predicting the severity and prognosis of IMN.

Objective:To evaluate the expression of tertiary lymphoid structures (TLS) in renal tissues, and the relationship between TLS and clinicopathological changes and prognosis in idiopathic membranous nephropathy (IMN) patients.Methods:It was a single center retrospective study. The patients with IMN diagnosed by renal biopsy at Shengjing Hospital Affiliated to China Medical University from January 2018 to December 2020 were enrolled, and their clinicopathological data were collected. Immunohistochemistry was used to evaluate the expression of TLS in renal tissues. According to whether TLS expression in renal tissues was positive or not, the patients were divided into TLS-positive group and TLS-negative group, and the baseline differences in clinicopathological data between the two groups were compared. The clinical remission included complete remission and partial remission. Logistic regression analysis was used to analyze the correlation between serum phospholipase A2 receptor (PLA2R) antibody titer and positive TLS expression in renal tissues. Kaplan-Meier survival curve and log-rank test were performed to analyze the differences of proteinuria remission rates between TLS-positive and TLS-negative groups. Cox regression analysis was employed to identify the related factors of proteinuria remission. The receiver operating characteristic (ROC) curve was used to evaluate the value of TLS in predicting proteinuria remission.Results:A total of 120 IMN patients were included in this study, with age of 50.00 (40.00, 57.75) years and 78 (65.00%) males. The 24-hour urinary protein was (7.54±4.14) g, 89 (74.17%) patients were positive for serum PLA2R antibody, and the serum PLA2R antibody titer was 90.49 (48.88, 155.33) RU/ml. Immunohistochemical results showed that TLS was mainly distributed in the renal cortex glomeruli or around renal blood vessels in renal tissues. There were 43 patients in the TLS-positive group and 77 patients in the TLS-negative group. The positive rate of serum PLA2R antibody in the TLS-positive group was 83.72% (36/43). Compared with the TLS-negative group, the TLS-positive group had lower serum albumin ( t=-3.474, P<0.001) and estimated glomerular filtration rate ( Z=-2.076, P=0.045), while serum creatinine ( t=2.006, P=0.028), 24-hour urinary protein ( t=4.140, P<0.001), serum PLA2R antibody titer ( Z=4.628, P=0.001), glomerulosclerosis degree ( Z=2.403, P=0.019), and proportions of hypertension ( χ2=6.511, P=0.011), renal interstitial fibrosis ( χ2=4.088, P=0.043), renal interstitial inflammatory cell infiltration ( χ2=9.261, P=0.002), tubular atrophy ( χ2=4.936, P=0.026) and extremely high-risk of kidney disease progression ( χ2=9.352, P=0.002) were higher. Multivariate logistic regression analysis showed that serum PLA2R antibody titer was an independent factor correlated with positive TLS expression in renal tissues ( OR=1.014, 95% CI 1.007-1.021). The median follow-up time was 18.00 (95% CI 16.07-19.93) months. Kaplan-Meier survival curve showed that the proteinuria remission rate in the TLS-positive group was lower than that in the TLS-negative group (Log-rank χ2=9.339, P=0.002). Cox regression analysis showed that positive TLS expression was an independent factor correlated with proteinuria remission ( HR=0.228, 95% CI 0.177-0.297). ROC curve showed that TLS had a certain clinical predictive value for proteinuria remission ( AUC=0.703, 95% CI 0.608-0.798). Conclusions:IMN patients with positive TLS expression in renal tissues have a lower proteinuria remission rate, more severe pathological damage, and a higher risk of disease progression. TLS is expected to become a pathological marker for predicting the severity and prognosis of IMN.

ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome， and to provide guidance for national medical decision-making， clinical drug promotion， and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （Trial Version， 2021） using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software， this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions， including safety pre- and post-market launch， effectiveness in treating migraine， economy （cost-effectiveness）， and innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics in both its technology and clinical applications. ResultSafety： Duliang soft capsules were found to have good safety based on evidence from known adverse reactions （spontaneous reporting system （SRS） data， literature data， etc.）， pre-marketing toxicological research， and post-marketing drug monitoring. Effectiveness： A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy： Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation： Duliang soft capsules， with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components， hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction （CO₂ supercritical extraction technology） and formulation （soft capsule） processes. The product's innovation was rated as "Better". Suitability： A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility： Duliang soft capsules are moderately priced， making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics： The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio （Shi Zhai Bai Yi Xuan Fang） from the Song Dynasty， and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue （Jing Yue Quan Shu） as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch， and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness， suitability， and accessibility， and outstanding TCM characteristics. The product's safety， economy， and innovation received good ratings. In summary， Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics， the evidence was sufficient， and the result was confirmed， providing crucial references for clinical decision-making and pharmaceutical management.

OBJECTIVE: To investigate the effect of microRNA-509-3p (miR-509-3p) on the apoptosis of atherosclerotic vascular endothelial cells. METHODS: Mouse aortic endothelial cells (MAECs) were divided into normal control group, oxidized low-density lipoprotein (ox-LDL) group, miR-509-3p overexpression group, miR-509-3p overexpression control group, miR-509-3p inhibitor + ox-LDL group, and miR-509-3p inhibitor control + ox-LDL group. MAEC were induced with 100 mg/L ox-LDL for 24 hours, and then transfected with miR-509-3p overexpression/inhibitor and corresponding control for 48 hours. The miR-509-3p expression in MAECs exposed to ox-LDL was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Flow cytometry was used to detect the level of apoptosis, and cell counting kit (CCK-8) was used to detect the proliferation activity of MAECs. The direct gene targets of miR-509-3p were predicted using bioinformatics analyses and confirmed using a dual luciferase reporter assay. The expression of Bcl-2 mRNA and protein was detected by RT-qPCR and Western blotting, respectively. RESULTS: Compared with the normal control group, miR-509-3p was significantly upregulated in ox-LDL-stimulated MAECs (1.68±0.85 vs. 1.00±0.30, t = 2.398, P < 0.05). After transfection of MAECs with miR-509-3p overexpression, the luciferase activity of the BCL2 3'UTR WT reporter gene was significantly lower than that of miR-509-3p overexpression control group (0.83±0.06 vs. 1.00±0.07, t = 4.531, P = 0.001). The luciferase activity of the BCL2 3'-UTR mutant (MUT) reporter gene was not significantly different from that of miR-509-3p overexpression control group (0.94±0.05 vs. 1.00±0.08, t = 1.414, P = 0.188). Compared with the normal control group and miR-509-3p mimics control group, the cell proliferation activity was decreased [(0.60±0.06)% vs. (1.00±0.09)%, (0.89±0.04)%, both P < 0.01], the percentage of apoptotic cells were increased [(23.46±2.02)% vs. (7.66±1.52)%, (10.40±0.78)%, both P < 0.05], and the mRNA and protein expression of Bcl-2 were significantly downregulated (Bcl-2 mRNA: 0.52±0.13 vs. 1.00±0.36, 1.10±0.19, Bcl-2 protein: 0.42±0.07 vs. 1.00±0.11, 0.93±0.10, both P < 0.01) in miR-509-3p overexpression group. Compared with the ox-LDL group, inhibition of miR-509-3p expression could increase the proliferation activity of MAECs induced by ox-LDL [(0.64±0.35)% vs. (0.34±0.20%)%, P < 0.05], and reduce the apoptosis rate [(13.59±2.22)% vs. (29.84±5.19)%, P < 0.01], and up-regulated the expression of Bcl-2 mRNA and protein in MAECs induced by ox-LDL (Bcl-2 mRNA relative expression: 0.82±0.09 vs. 0.52±0.10, Bcl-2 protein relative expression: 0.83±0.17 vs. 0.40±0.07, both P < 0.05). CONCLUSIONS Bcl-2 was one of the target genes of miR-509-3p. miR-509-3p can reduce the proliferation activity of endothelial cells, reduce the expression of Bcl-2, and promote cell apoptosis, thereby promoting the occurrence and development of atherosclerosis. Inhibition of miR-509-3p expression may be a potential therapeutic target for atherosclerosis.
Animals ; Mice ; Humans ; Endothelial Cells ; MicroRNAs/metabolism* ; Signal Transduction ; Lipoproteins, LDL/metabolism* ; Apoptosis ; RNA, Messenger/metabolism* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; Atherosclerosis/metabolism* ; Luciferases/pharmacology* ; Cell Proliferation ; Human Umbilical Vein Endothelial Cells