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.

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.

Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

Traditional Chinese medicine(TCM) processing is a specialized pharmaceutical technique with the primary objective of reducing the toxicity of medicinal substances. Euphorbia pekinensis, E. ebracteolata, and E. fischeriana, all belonging to Euphorbiaceae, are classified as drastic purgative herbs, traditionally used for eliminating retained water, reducing swelling, resolving toxicity, and dispersing masses. However, these herbs are also associated with adverse effects such as abdominal pain and diarrhea. Accordingly, they are commonly processed with vinegar, milk, or Terminalia chebula decoction to reduce the toxicity. This review summarizes the chemical constituents, pharmacological activities, historical evolution of processing methods, and detoxification mechanisms of the three toxic Euphorbia species. The primary toxic constituents are terpenoids. Specifically, E. ebracteolata and E. fischeriana are rich in diterpenoids, while E. pekinensis contains diterpenoids, triterpenoids, and sesquiterpenoids. Studies have shown that vinegar processing promotes structural transformations of diterpenoids, including ether bond hydrolysis, lactone ring opening, esterification, oxidation, and epoxide ring cleavage, thereby reducing the content and toxicity of these compounds. Milk processing facilitates the dissolution of toxic components into the residual liquid of excipients, leading to decreases in their concentrations in the final decoction pieces. Processing with T. chebula decoction raises the levels of tannin-derived phenolic acids, which antagonize the adverse effects of the intestine. These findings reveal a shared detoxification pattern among the three toxic herbs. Accordingly, this review proposes the concept of a shared detoxification mechanism for toxic herbs belonging to the same family or genus. That is, toxic herbs belonging to the same taxon often exhibit similar toxicological profiles and can undergo detoxification through the same processing methods, reflecting common underlying mechanisms. Investigating such shared mechanisms across multiple species of the same genus offers a promising research strategy. Ultimately, the research into processing-induced detoxification mechanisms provides both theoretical and practical support for ensuring the safety of toxic TCM.
Euphorbia/classification* ; Drugs, Chinese Herbal/metabolism* ; Humans ; Animals ; Inactivation, Metabolic ; Medicine, Chinese Traditional

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the effect of femoral condyle sliding osteotomy (FCSO) on the flexion gap and external rotation of the prosthesis in balancing coronal instability during initial total knee arthroplasty (TKA). METHODS: Between November 2021 and October 2024, FCSO technique was applied to balance the coronal medial and lateral spaces during initial TKA in 3 patients, including medial condyle sliding osteotomy (MCSO) and lateral condyle sliding osteotomy (LCSO). There were 1 male and 2 females with the age of 81, 68, and 68 years old. The affected knee has varus or valgus deformity, with tibia-femoral angles of 169.7°, 203.3°, and 162.2°, respectively. The hip-knee-ankle angle (HKA), range of motion (ROM), knee society scoring system (KSS), and pain visual analogue scale (VAS) score were used to evaluate joint function and pain relief. Based on model bone, the thickness and bone bed area of the medial and lateral femoral condyle osteotomy blocks in FCSO were measured. During TKA in 12 patients, the range of osteotomy block movement was evaluated. By simplifying the upward and forward movement of the osteotomy block into a geometric model, the impact of movement on the flexion gap and external rotation of the prosthesis was calculated. RESULTS: After application of FCSO during TKA, the limb alignment and medial and lateral balance at extension and flexion positions were restored in 3 patients. Three patients were followed up 23, 11, and 3 months, respectively. Postoperative HKA, pain VAS score, KSS score, and ROM all showed significant improvement compared to preoperative levels. The maximum thickness of osteotomy blocks by MCSO and LCSO was 17 and 12 mm, respectively. The simple upward movement of the osteotomy block mainly affected the extension gap, and had little effect on the flexion gap and external rotation of the prosthesis. Moving the osteotomy block forward at the same time had a significant impact on the flexion gap and external rotation of the prosthesis, especially on LCSO. Mild forward movement leaded to a decrease in external rotation of more than 3°, which had a serious impact on the patellar trajectory. CONCLUSION FCSO can effectively solve the problem of imbalance between the medial and lateral spaces during initial TKA, avoiding knee joint instability caused by excessive loosening and limiting the use of constrained condylar prosthesis. The distance for the downward movement of the osteotomy block in MCSO and LCSO was 3-5 mm and 6-8 mm, respectively, with 10-15 mm of space for forward movement and almost no space for backward movement. For MCSO, the upward and forward movement of the osteotomy block will increase the external rotation of the prosthesis, which is beneficial for improving the patellar trajectory and suitable for valgus knee. LCSO is suitable for varus knee, and the osteotomy block only slides vertically up and down without moving forward and backward.
Humans ; Osteotomy/methods* ; Male ; Female ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Range of Motion, Articular ; Femur/surgery* ; Knee Joint/physiopathology* ; Aged, 80 and over ; Knee Prosthesis ; Treatment Outcome ; Osteoarthritis, Knee/surgery*

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People