The chemical constituents in dried roots of Atractylodes macrocephala were investigated in this study. Through utilizing normal-phase silica gel and ODS column chromatography, TLC, and semi-preparative HPLC, 4 new sesquiterpenoids were purified from the ethyl acetate extract of A. macrocephala. By various spectroscopic techniques, such as 1D and 2D NMR, HR-ESI-MS, IR, UV, and CD, their structures were identified as atractylmacron A (1), 9β-hydroxyasterolide (2), atractylenolide H (3), atractylenolide J (4). Compound 1 possesses a rare 6/7 bicyclic skeleton.

The circadian clock is an endogenous time-keeping system that maintains physiological homeostasis by integrating environmental and genetic interactions. Heart failure is a complex clinical syndrome characterized by structural abnormalities and/or functional impairment of the heart. Growing evidence suggests that core circadian components, such as BMAL1 and REV-ERBα, play important roles in modulating myocardial energy metabolism, inflammatory responses, and oxidative stress, contributing to myocardial structural and metabolic remodeling during heart failure progression. Notably, circadian disruption is closely associated with heart failure, with aberrant blood pressure rhythms and disturbances in the sleep-wake cycle in patients. The time-dependent efficacy of heart failure medications further supports the potential of chronotherapy-based strategies to improve clinical outcomes. Here, we summarize the multifaceted regulatory roles of the circadian clock, particularly core clock genes, in heart failure pathogenesis, providing a theoretical framework for developing personalized chronotherapeutic strategies for heart failure management.
Humans ; Heart Failure/physiopathology* ; Circadian Rhythm/physiology* ; Circadian Clocks/physiology* ; ARNTL Transcription Factors/physiology* ; Nuclear Receptor Subfamily 1, Group D, Member 1/physiology* ; Oxidative Stress ; Energy Metabolism ; Animals

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective To develop a damage control operation(DCO)simulation training platform for traumatic brain injury(TBI)in wartime based on mixed reality to open up a new path for surgical skills training of military surgeons.Methods The platform mainly consisted of wartime TBI DCO simulation training software,a surgical manikin and a HoloLens 2 MR device.The simulating training software was developed with C# language and the technologies of MR,basic gestures,spatial scanning positioning and etc on the basis of constructed surgical decision-making training system,virtual surgical environment and functional modules.The surgical manikin was customized with reference to the standard body type of an adult male with a height of 180 cm,and an electronic chip was developed and placed inside the head of the manikin to execute data matching with the simulation training software.The simulation training software was installed and run in the HoloLens 2 MR device to realize TBI DCO simulation training on the virtual reality interactive model.Results The platform developed implemented the functions of virtual reality interactive model reset positioning,operation simulation training,examination and on-site demonstration,which gained advantages in stimulating learning interest and facilitating risk-free,time-and space-indepen-dent,immersive and interactive learning and was generally recognized by the trainees.Conclusion The simulation training platform can be a supplementary to other training means to improve the ability of military surgeons in damage control operation.[Chinese Medical Equipment Journal,2024,45(2):17-21]

Objective:To explore the application of game-based teaching combined with Jeffries simulation teaching in training orthopedic trauma nursing interns.Methods:Totally 120 intern nurses who received orthopedic trauma nursing training from 2021 to 2023 were selected. They were divided into two groups according to their start dates, with 60 nurses in each group. The control group (started before December 2022) adopted routine teaching, whereas the observation group received game-based teaching combined with Jeffries simulation teaching. The assessment results, core competence [Competency Inventory for Registered Nurse (CIRN)], and learning enthusiasm [Active Learning Scale (ALS)] were compared both between the groups and within each group before and after the training. The course experience [Course Experience Questionnaire (CEQ)] of the trainees after training was recorded.Results:After the internship, the theoretical exam scores [(89.64±6.73) vs. (83.71±6.20)], practical operation scores [(80.82±5.94) vs. (75.61±5.73)], CIRN scores [(180.69±7.61) vs. (157.33±6.83)], and ALS scores [(89.48±6.83) vs. (73.22±6.25)] of two groups of nursing students increased compared to their scores before the internship, and the observation group showed significantly higher scores than the control group ( P<0.05). After the internship, the CEQ score was higher in the observation group than in the control group [(49.65±2.58) vs. (36.57±1.94)]. Conclusions:In the training of orthopedic trauma nursing interns, game-based teaching combined with Jeffries simulation teaching can not only improve course experience and learning enthusiasm, but also enhance the assessment results, core competence, and critical thinking.

Objective To study the effect of silencing ubiquitin-conjugating enzyme 2C(UBE2C)on the proliferative capacity of human breast cancer cells MCF-7 and to preliminarily investigate its mechanism of action.Methods Silencing of UBE2C gene in MCF-7 cells using small interfering RNA(si-RNA).CCK-8 assay and clone formation assay were used to detect cell proliferation a-bility.The expression of cell cycle-associated protein kinase inhibitor protein p21 as well as cell cycle-promoting proteins CyclinD1,cyclin-dependent kinase 4(CDK4),and cyclin-dependent kinase 6(CDK6)were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot at the mRNA and protein levels,respectively.Results Compared with the cells in blank control group and negative control(si-NC)group,the expression of UBE2C was down-regulated in cells of si-UBE2C group.The re-sults of CCK-8 assay and clone formation assay showed that the proliferative ability of cells in si-UBE2C group was significantly de-creased.Compared with the cells in blank control group and si-NC group,the expression of cell cycle-related protein kinase inhibitor protein p21 in the cells of si-UBE2C group was up-regulated at both the mRNA and protein levels,while the expression of cell cycle-promoting proteins CyclinD1,CDK4 and CDK6 was down-regulated at both the mRNA and protein levels.Conclusion UBE2C can reg-ulate the proliferative capacity of MCF-7 cells and promote breast cancer progression by mediating the expression of CyclinD1/CDK4/CDK6 complex and p21.

Hydrogen sulfide,as a third gas signal molecule and neurotransmitter,can play a neuroprotective role by anti-oxidative stress,anti-inflammatory response,metabolic inhibition and other mechanisms.It is of great significance for the occurrence and development of neurodegenerative diseases including Alzheimer's disease(AD)and Parkinson's disease(PD)mediated by neuroinflammation.This article reviews the research progress of hydrogen sulfide and neuroinflammation and its mediated neurodegenerative diseases,so as to provide new ideas for the treatment of neurodegenerative diseases.

AIM:To investigate the molecular mechanisms of KG-1 cell proliferation by profiling its responses to various protein kinase inhibitors.METHODS:CCK-8 assay,real time quantitative PCR(qRT-PCR)and Western-blot were used to detect the effect of various protein kinase inhibitors on KG-1 cell proliferation,the expression levels of mRNA and phosphorylation level of signaling pro-teins in the FGFR1 downstream pathways.RE-SULTS:NVP-BGJ398 and PD173074 effectively in-hibited the proliferation of KG-1 cells,indicative of a crucial role of FGFR downstream signaling.After treatment with FGFR inhibitors,the levels of p-FG-FR1OP2-FGFR1 and p-STAT5 decreased significantly(P<0.001),p-AKT decreased slightly(P<0.05),with-out affecting the p-ERK level(P>0.05).CONCLU-SION:FGFR1OP2-FGFR1 mainly acts on the down-stream STAT5 signaling pathway to promote cell proliferation.Comprehensive protein kinase inhibi-tion analysis is a reliable and direct approach to identify functional drivers of cancer cell prolifera-tion.