Objective To investigate the regulatory effect and molecular mechanism of circ_0044556 on the malignant biological behavior of triple negative breast cancer(TNBC)cells by targeting the miR-338-3p/bromodomain-containing protein 4(BRD4)axis.Methods The TargetScan online website was used to predict the binding sites of circ_0044556 with miR-338-3p and miR-338-3p with BRD4.Dual-luciferase reporter gene assays were performed to determine the relationship among circ_0044556,miR-338-3p,and BRD4 in MDA-MB-231 cells.Quantitative real-time PCR(qRT-PCR)and Western blotting were employed to detect the expression of circ_0044556,miR-338-3p,and BRD4 protein in human TNBC cell line MDA-MB-231 and human normal breast epithelial cells MCF-10A.MDA-MB-231 cells were divided into NC group,si-NC group(transfected with si-NC),si-circ_0044556 group(transfected with si-circ_0044556),si-circ_0044556+inhibitor NC group(transfected with si-circ_0044556 and inhibitor NC),and si-circ_0044556+miR-338-3p inhibitor group(transfected with si-circ_0044556 andmiR-338-3p inhibitor).qRT-PCR was applied to detect the expression of circ_0044556 and miR-338-3p;Western blotting was used to detect the expression of BRD4,E-cadherin,N-cadherin and Vimentin;the CCK-8 assay was applied to detect cell proliferation;flow cytometry was applied to detect cell apoptosis;and Transwell assays were used to detect cell invasion and migration.Thirty nude mice were randomly divided into NC group(tail vein injection of normal saline),si-NC group(tail vein injection of LV-NC),si-circ_0044556 group(tail vein injection of LV-circ_0044556),si-circ_0044556+inhibitor NC group(tail vein injection of LV-circ_0044556 and antiagomir NC),and si-circ_0044556+miR-338-3p inhibitor group(tail vein injection of LV-circ_0044556 and antiagomir miR-338-3p),with 6 mice per group.A xenograft tumor model was constructed by subcutaneous injection of MDA-MB-231 cells into nude mice,and tumor volume and weight were measured.Results TargetScan prediction results showed that the downstream miRNA of circ_0044556 was miR-338-3p,and the downstream target gene of miR-338-3p might be BRD4.Compared with transfecting mimic NC,transfection with miR-338-3p mimic significantly reduced the luciferase activities of WT-circ_0044556(0.34±0.03 vs.1.00±0.15,P<0.05)and WT-BRD4(0.41±0.05 vs.1.05±0.13,P<0.05)in MDA-MB-231 cells.Compared with MCF-10A cells,the expression levels of circ_0044556 and BRD4 protein in MDA-MB-231 cells were significantly increased,while the expression level of miR-338-3p was significantly decreased(P<0.05).Compared with NC group and si-NC group,the expression levels of circ_0044556,the protein expression levels of BRD4,N-cadherin,and Vimentin,and the OD450 value in MDA-MB-231 cells of si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05),the number of migrated and invaded cells was significantly reduced(P<0.05),and the expression level of miR-338-3p,the protein expression level of E-cadherin,and the cell apoptosis rate in MDA-MB-231 cells were significantly increased(P<0.05);downregulation of miR-338-3p rescued the inhibitory effect of circ_0044556 knockdown on invasion,migration,and proliferation of MDA-MB-231 cells.Compared with NC group and si-NC group,the tumor volume and weight in si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05);compared with si-circ_0044556 group and si-circ_0044556+inhibitor NC group,the tumor volume and weight in si-circ_0044556+miR-338-3p inhibitor group were significantly increased(P<0.05).Conclusion circ_0044556 may promote the malignant biological behaviors of TNBC cells through the miR-338-3p/BRD4 axis.

OBJECTIVE: This study examines utilizes the advantages of machine learning algorithms to discern key determinants in prognosticate postoperative circulatory complications (PCCs) for older patients. METHODS: This secondary analysis of data from a randomized controlled trial involved 1,720 elderly participants in five tertiary hospitals in Beijing, China. Participants aged 60-90 years undergoing major non-cardiac surgery under general anesthesia. The primary outcome metric of the study was the occurrence of PCCs, according to the European Society of Cardiology and the European Society of Anaesthesiology diagnostic criteria. The analysis metrics contained 67 candidate variables, including baseline characteristics, laboratory tests, and scale assessments. RESULTS: Our feature selection process identified key variables that significantly impact patient outcomes, including the duration of ICU stay, surgery, and anesthesia; APACHE-II score; intraoperative average heart rate and blood loss; cumulative opioid use during surgery; patient age; VAS-Move-Median score on the 1st to 3rd day; Charlson comorbidity score; volumes of intraoperative plasma, crystalloid, and colloid fluids; cumulative red blood cell transfusion during surgery; and endotracheal intubation duration. Notably, our Random Forest model demonstrated exceptional performance with an accuracy of 0.9872. CONCLUSION We have developed and validated an algorithm for predicting PCCs in elderly patients by identifying key risk factors.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; Machine Learning ; Postoperative Complications/etiology* ; Risk Factors ; Randomized Controlled Trials as Topic ; Secondary Data Analysis

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

The effective implementation of clinical practice guideline(CPG), as a crucial vehicle of evidence-based medicine, plays a vital role in improving healthcare quality and patient safety. Currently, there remains a significant gap between the actual implementation outcomes of traditional Chinese medicine(TCM) guidelines and their intended objectives, which necessitates a systematic investigation into their influencing factors to optimize implementation strategies. This study aims to comprehensively identify the factors influencing CPG implementation in China, adapt the theoretical domains framework(TDF) to the local context, and integrate TCM-specific characteristics to provide recommendations for optimizing the development and implementation processes of TCM guidelines. Systematic search was conducted across multiple databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, and EMbase, covering the period from each database's inception to March 2024. Qualitative and mixed-methods studies were included to examine factors affecting the implementation of clinical practice guidelines. The methodological quality of the included studies was assessed using the critical appraisal skills programme(CASP) tool. RESULTS:: were synthesized through framework analysis and thematic synthesis, and expert consensus was achieved via a structured consensus meeting. A total of 16 studies involving 2 388 participants were included with overall good methodological quality. Based on the TDF, 43 influencing factors across 14 domains were identified. The most critical factors included the quality of guideline evidence, training and academic conferences organized by hospitals and academic institutions to promote guideline adoption among medical staff, support from professional leaders for guideline implementation, the applicability and clarity of guideline recommendations, and material resources(supplies, funding, and facilities) required for implementation. Additionally, influencing factors of TCM guideline implementation were identified, including the distinctive advantages of TCM therapies, the applicability of syndrome differentiation, and the feasibility of TCM treatments. Based on these findings, it is recommended that TCM guideline development should incorporate these unique influencing factors to formulate high-quality, clear, and actionable recommendations. Following guideline publication, healthcare and academic institutions should strengthen training and dissemination efforts and ensure the availability of necessary implementation resources to facilitate the successful adoption of guidelines in clinical practice.
China ; Humans ; Practice Guidelines as Topic ; Medicine, Chinese Traditional/standards* ; Evidence-Based Medicine

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China