AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1 000,100,and 10 μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10 μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1 000 μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10 μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endothelial growth factor A,and hypoxia-inducible factor α,and thereby influenced angiogenesis during bone repair.(2)Network pharmacological analyses indicated that Echinops sphaerocephalus L.may bind to eight core targets(TGFB1,TNF,IL-6,STAT3,CTNNB1,IL-1B,AKT1,and HIF-1A)through four core active components(apigenin,caffeic acid,quercetin,and chlorogenic acid)to exert an effect on angiogenesis,atherosclerosis,multiple viral infections,and tumor angiogenesis-related signaling pathways.

BackgroundAgomelatine， a novel antidepressant with dual efficacy in mood improvement and sleep regulation， has been widely utilized in clinical treatment of depressive disorders. The association between agomelatine and hepatic dysfunction has garnered increasing attention， yet there remains limited research on its long-term effect of liver function in real clinical scenarios. ObjectiveTo investigate the effect of different doses of agomelatine on liver function in patients with depressive disorders in real clinical scenarios， and to ascertain its safety profile and efficacy differences. MethodsA retrospective study was conducted， enrolling 200 patients diagnosed with depressive disorders according to the International Classification of Diseases， tenth edition （ICD-10）， who received agomelatine treatment at the Department of Psychiatry of Chaohu Hospital Affiliated to Anhui Medical University from January 2019 to December 2024. Longitudinal follow-up was performed based on real-world data. Patients were divided into a low-dose group （25 mg/d） （n=121） and a high-dose group （50 mg/d） （n=79） based on their agomelatine dosage. Follow-up assessments were conducted at baseline， the 2^nd， 6^th， 14^th， and 26^th weeks after treatment initiation. Liver function indicators， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBIL）， were measured using a fully automated biochemical analyzer. Clinical symptoms were evaluated using the Hamilton Depression Scale-24 item （HAMD-24） and the Hamilton Anxiety Scale （HAMA）. ResultsNo statistically significant time effect， intergroup effect， or time-by-group interaction effect was observed for ALT， AST， or TBIL in either the low-dose or high-dose group （P>0.05）. The time effects for both HAMD-24 and HAMA scores in the two groups were statistically significant （F_time=430.573， 395.737， P<0.01）. From the end of the 2^nd week of treatment onward， the scores at each follow-up time point were significantly lower than those at the baseline period （P<0.01）. ConclusionBoth low-dose and high-dose agomelatine may have no significant effect on liver function in patients with depressive disorders， with no difference in liver function impairment was observed between dosage groups. Low-dose and high-dose agomelatine may be equally effective in alleviating depressive and anxiety symptoms in patients with depressive disorders. ［Funded by the Education Work Committee of the Anhui Provincial Committee for Outstanding Young Talents in Colleges and Universities （number， gxyqZD2022022）； the Key Project of Scientific Research Fund of Anhui Institute of Translational Medicine （number， 2023zhyx-B18）］

Objective:To investigate the prevalence and severity of symptom burden among long-term survivors of oropharyngeal cancer after radiotherapy, to identify core symptom clusters, and to explore their correlation with quality of life.Methods:A previous retrospective study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences on patients with oropharyngeal cancer who underwent radiotherapy between January 2010 and December 2020. Patients who were still alive as of December 2023 were further followed and analyzed. From December 2023 to August 2024, symptom burden and quality of life were assessed using the Chinese version of the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Exploratory factor analysis (principal component analysis with Promax rotation) were used to identify symptom clusters. Spearman correlation analysis was performed to explore the relationship between total symptom cluster scores and standardized domain scores of quality of life. Multivariate linear regression analysis was further employed to determine the relationship between identified symptom clusters and overall quality of life.Results:A total of 273 patients were included, with a median follow-up duration of 6.2 years (range: 3.5-14.5 years) and a median age of 61 years (range: 27-88 years) at follow-up. The top 5 incidence rates of symptom reported by patients were mucus problems in the mouth or throat (147 cases, 53.8%), dental or gum issues (143 cases, 52.4%), xerostomia (140 cases, 51.3%), difficulty swallowing or chewing (95 cases, 34.8%), and taste disturbance (79 cases, 28.9%). Among them, xerostomia was the most serious symptom. The most frequently reported interference was impact on work (including household chores) (55 cases, 20.1%). Exploratory factor analysis identified 3 symptom clusters: fatigue-nausea cluster, eating-voice cluster, and xerostomia-sleep cluster, all of which were significantly correlated with lower overall quality of life of patients (all P<0.001). Conclusion:Long-term survivors of oropharyngeal cancer after radiotherapy experience substantial symptom burden. The fatigue-nausea, eating-voice, and xerostomia-sleep clusters are the core symptom clusters impacting quality of life.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To explore the influence of artificial intelligence(AI)-assisted compressive sensing(ACS)technique with different acceleration factors on the image quality and scan time of three dimensional time-of-flight magnetic resonance angiography(3D-TOF-MRA)for brain.Methods:Thirty participants who underwent brain magnetic resonance imaging(MRI)at Tongzhou Branch of Beijing Friendship Hospital were recruited.All subjects underwent imaging scans about four different parameters:a non-accelerated technique(control group),ACS technique integrated with acceleration factor of 4.03(ACS4 group),ACS technique integrated with acceleration factor of 5.02(ACS5 group),and ACS technique integrated with acceleration factor of 6.06(ACS6 group).The image clarity,ranking of imaging capabilities of distal branch blood vessels and the ratio of pseudo-stenosis were qualitatively analyzed.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),edge sharpness,and scan time were quantitatively analyzed.Results:There was not difference in vessel clarity among three ACS groups at the proximal and middle intracranial segments.For distal segments of blood vessel,the ACS4 group[3.0(3.0,3.0)]and ACS5 group[3.0(3.0,3.0)]were better than ACS6[2.5(2.0,3.0)](q=29.800,27.500,P<0.05).The imaging capabilities of distal-branch vessel of ACS4 group and ACS5 group were better than ACS6 group.There was no stenosis in the proximal and middle segments of the images of the three ACS group,and there were no stenosis in the images of distal vessels of ACS4 group and ACS5 group.A total of 5 cases were pseudo-stenosis in the distal vessels of ACS6 group.Compared with the control group,the incidence of pseudo-stenosis in the distal vessels of ACS6 group was 16.7%.The SNR and CNR values of quantitative analysis for proximal vessels in ACS6 group were higher than them in ACS4 group(q=27.800,26.200,P<0.05),and there was not significant difference in them among ACS4 group,ACS6 group and ACS5 group(P>0.05).The differences of SNR and CNR values in the middle and distal segments of blood vessels among different groups were not significant(P>0.05).There was not significant difference in the edge sharpness of blood vessels among ACS4 group,ACS5 group,and ACS6 group(P>0.05),while all of them were higher than those of control group,and the differences were significant(q=48.150,53.367,44.883,P<0.001).Compared with control group,the scan-time of ACS4 group was reduced by 55.19%,and that of ACS5 group was reduced by 64.07%,and that of ACS6 group was reduced by 70%.Conclusion:ACS technique can accelerate the imaging speed of brain 3D-TOF-MRA and ensure image quality.It is clinically recommended to set the ACS acceleration factor as 5.02 to undergo brain 3D-TOF-MRA scans.

Objective:To evaluate the application value of interactive learning in enhancing the diagnosis of breast cancer by residents in the department of radiology through training based on the interpretation of breast magnetic resonance imaging (MRI) features by the breast imaging reporting and data system (BI-RADS).Methods:A total of 23 trainees completed BI-RADS standardized reports of 250 cases. These cases were divided into a pre-training group (Group 1) and post-training groups (initial training, Groups 2-4; advanced training, Groups 5-6), forming a total of six groups. The efficacy of interactive learning through course lectures and case-based practice in enhancing their ability in breast cancer diagnosis was analyzed. All trainees generated reports based on the BI-RADS scoring criteria. Interpretation agreement rates, evaluation time, and confidence levels were recorded. SPSS 25.0 was used for independent samples t test, chi-square test, and rank-sum test. Results:During the initial stage of training, the agreement rate of 150 cases reached 80.00%, which was recommended as the endpoint for completion of the initial learning phase. A significant difference existed between Group 4 and Group 1 ( P=0.012) in agreement rate. Statistically significant differences were noted in evaluation time for Groups 5 and 6 before and after advanced training ( P=0.001 and 0.007, respectively). A significant difference in confidence level was observed for Group 5 ( P=0.005). Conclusions:Interactive training based on BI-RADS standardized reporting can improve the diagnosis of breast diseases by residents in the department of radiology, particularly for enhancing the quality of reports for mass-like enhancement breast diseases.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.